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Sample records for acute oral toxicity

  1. Acute oral toxicity test of chemical compounds in silkworms.

    Science.gov (United States)

    Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

  2. Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

    Science.gov (United States)

    Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

    2018-02-05

    Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC

  3. Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

    African Journals Online (AJOL)

    fisiologia

    2012-09-18

    Sep 18, 2012 ... In the acute toxicity of Nv-EtOH, behavioral and physiological alterations were not observed neither animal's death in the doses of 2.0 g/kg intraperitoneally and 5.0 g/kg orally, respectively indicating low toxicity of the extract. In this experiment, it was observed that the. Nv-EtOH has LD50 > 5000 mg/kg.

  4. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

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    Wuen Yew Teoh

    2013-01-01

    Full Text Available Gynura bicolor (Compositae which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116, one human breast adenocarcinoma cell line (MCF7, and one human normal colon cell line (CCD-18Co were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay, possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.

  5. Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

    International Nuclear Information System (INIS)

    Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C.

    1990-01-01

    The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02)

  6. Acute and sub-chronic oral toxicity studies of methanol extract of ...

    African Journals Online (AJOL)

    Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Norhafizah Mohtarrudin, Arifah Abdul Kadir, Manraj Singh Cheema, Zuraini Ahmad, Ching Siew Mooi, Siti Farah Md. Tohid ...

  7. Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

    Directory of Open Access Journals (Sweden)

    Idania Rodeiro

    2018-02-01

    Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

  8. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    Science.gov (United States)

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

    Science.gov (United States)

    Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

    2018-02-01

    In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The Acute Oral Toxicity of Commonly Used Pesticides in Iran, to Honeybees (Apis Mellifera Meda

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    Rasuli Farhang

    2015-06-01

    Full Text Available The honey bee is credited with approximately 85% of the pollinating activity necessary to supply about one-third of the world’s food supply. Well over 50 major crops depend on these insects for pollination. The crops produce more abundantly when honey bees are plentiful. Worker bees are the ones primarily affected by pesticides. Poisoning symptoms can vary depending on the developmental stage of the individual bee, and the kind of chemical employed. The oral toxicity of these insecticides: (phosalone and pirimicarb, acaricide (propargite, insecticide and acaricide (fenpropathrin, fungicides, and bactericides (copper oxychloride and the Bordeaux mixture, were evaluated for the purposes of this research. The results showed that fenpropathrin had high acute oral toxicity (LC50-24h and LC50-48 were 0.54 and 0.3 ppm, respectively. Propargite had 7785 ppm (active ingredient for LC50-24h and 6736 ppm (active ingredient for LC50-48h in honeybees and is therefore, non-toxic to Apis mellifera. On the other hand, copper oxychloride had minimum acute oral toxicity to honeybees (LC50-24h and LC50-48 were 4591.5 and 5407.9 ppm, respectively and was therefore considered non-toxic. Also, the Bordeaux mixture was safe to use around honeybees. Phosalone and primicarb were considered highly and moderately toxic to honeybees, respectively.

  11. Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

    2018-02-01

    Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

  12. Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

    Science.gov (United States)

    Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

    2016-10-01

    Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Acute and sub-chronic oral toxicity studies of erythritol in Beagle dogs.

    Science.gov (United States)

    Eapen, Alex K; de Cock, Peter; Crincoli, Christine M; Means, Charlotte; Wismer, Tina; Pappas, Christopher

    2017-07-01

    Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

    Science.gov (United States)

    Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

  15. Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken sternal cartilage preparation.

    Science.gov (United States)

    Schauss, A G; Merkel, D J; Glaza, S M; Sorenson, S R

    2007-02-01

    Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

  16. Acute toxicity from baking soda ingestion.

    Science.gov (United States)

    Thomas, S H; Stone, C K

    1994-01-01

    Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

  17. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

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    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  18. Effect of gamma irradiation on acute oral toxicity of ethanolic extract of red ginger (zingiber officinale)

    International Nuclear Information System (INIS)

    Ermin Katrin; Winarti Andayani; Susanto; Hendig Winarno

    2014-01-01

    Red ginger is widely used in traditional medicine to treat various types of diseases. Evaluation of the toxic properties of red ginger is very important to know the negative harmful impact to human health. Therefore, before it is consumed by humans, it is needed to conduct acute oral toxicity of red ginger extract in mice. Thin rhizome of red ginger in poly ethylene plastic packaging was irradiated by gamma rays at a dose of 10 kGy with a dose rate of 10 kGy/h. The ethanol extract of unirradiated as well as irradiated red ginger was then tested for the acute oral toxicity using OECD Guideline test method. The results showed that throughout the 14 days of treatment there was a change in behavior pattern, clinical symptoms and body weight of control mice and treatment groups. Histopathological examination of kidneys, heart, liver, lungs and spleen of the dose less than 1250 mg/kg body weight showed normal condition and no significant side effects observation. While central venous damage and a reduced number of hepatocyte cells in male mice occurred in the test dose higher than 2000 mg/kg body weight, whereas in female mice it occurred in the test group dose higher than 1250 mg/kg bw. Based on renal histology of male and female mice at doses higher than 1250 mg/kg body weight, there were damage to Bowman's capsule, glomerulus, proximal vessel and distal vessels. LD50 of unirradiated and irradiated with 10 kGy of ethanol extract of red ginger were 1887 mg/kg body weight and 2639 mg/kg body weight, respectively, and it can be categorized as moderately toxic. Oral administration of ethanol extract of red ginger with dose of 1250 mg/kg body weight gave an effect in mice organs. From these results it can be concluded that oral administration of both unirradiated and irradiated with a dose 10 kGy of ethanol extract consider safe at a dose less than 1250 mg/kg body weigh. (author)

  19. Phytochemistry, Brine shrimp lethality and mice acute oral toxicity studies on seed extracts of Vernonia anthelmintica.

    Science.gov (United States)

    Jamil, Subia; Khan, Rafeeq Alam; Afroz, Syeda; Ahmed, Shadab

    2016-11-01

    Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)μg/ml and 216.11μg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46μg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

  20. Acute and Sub-Acute Oral Toxicity Evaluation of Astragalus hamosus Seedpod Ethanolic Extract in Wistar Rats

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    Mohammadmehdi Hassanzadeh-Taheri

    2018-03-01

    Full Text Available Background: Oral consumption of Astragalus hamosus L. (AH seedpod has been widely prescribed in traditional medicine system. However, its toxicity evaluation has never been investigated. Hence, the current study was performed to evaluate the toxicological profile of AH seedpod in acute and subacute assessments based on the OECD-guidelines 425 and 407 in male and female Wistar rats. Methods: In the acute study, ethanolic extract of AH at a single dose of 2000 mg/kg was orally administrated to six female rats. In the subacute assay, AH at the three different oral doses (75, 150 and 300 mg/kg were administrated to both male and female rats for 28 consecutive days. Results: No death or behavioural changes were observed in the treated animals. In subacute test, in both sexes, no changes in organ weights observed. Biochemically, compared to the control, AH at the dose of 300 mg/kg slightly increased (p<0.05 uric acid and creatinine and declined total cholesterol levels in both male and female rats. However, there is no statistically difference in other parameters such as albumin, triglyceride, blood urea, aspartate aminotransferase and alanine aminotransferase between AH treated groups and untreated controls. Hematologic parameters showed that AH at the maximum dose decreased red blood cells count only in male rats. Histopathological evaluation of liver and kidney exhibited no noticeable alterations in AH treated animals. Conclusion: It could be concluded that high excessive and long term consumption of AH may lead to renal dysfunction and deficiency in hematopoietic system.

  1. Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

    Science.gov (United States)

    Ahmad, Feroz; Tabassum, Nahida

    2013-01-01

    To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

  2. Acute Oral Toxicity of 3-Chloro-4,4-dimethyl-2-oxazolidinone (Compound 1) in ICR Mice

    Science.gov (United States)

    1990-10-01

    number) FIELD GROUP SUB-GROUP Acute Oral Toxicity, N- Chloramine , Mouse, Mammalian Toxicology, Water Disinfectant , 3-Chloro-4, 4 -dimethyl-2...Amer Ind Hyg Assoc Q 1943; 10:93-96. 7. Mora EC, Kohl HH, Wheatley WB, et al. Properties or a new chloramine disinfectant and detoxicant. Poultry Sci...ORGANIZATION Mammalian Toxicology (If applicable) US Army Biomedical Research Division of Toxicology SGRD-ULE- T and Development Laboratory 6c. ADDRESS

  3. Acute and Sub-chronic (28-day) Oral Toxicity Studies of ...

    African Journals Online (AJOL)

    Erah

    was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats. Methods: In the acute test, the ... associated with navel in children [4], and in the treatment of ... Ethical Committee for Teaching and. Research (ref no.

  4. Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

    Science.gov (United States)

    Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan; Kim, Woo Kyoung

    2018-03-01

    Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg.

  5. Acute and chronic toxicity studies of the water extract from dried ...

    African Journals Online (AJOL)

    Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results ...

  6. Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

    Science.gov (United States)

    Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

    2002-01-01

    The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

  7. Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

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    Akram Ghadirkhomi

    2016-08-01

    Full Text Available Objective: Pinus eldarica (P. eldarica is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50 of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels.  There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (pConclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg.

  8. An evaluation of acute toxicity of colloidal silver nanoparticles.

    Science.gov (United States)

    Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

    2011-11-01

    Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

  9. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    Science.gov (United States)

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  10. Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

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    Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

    2016-12-01

    Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

  11. Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran, E-mail: baskaranv@cftri.res.in

    2016-12-01

    Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100 mg/kg body weight (BW) and examined for 2 weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10 mg/kg BW for 4 weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140 nm and − 44 mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10 mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p < 0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. - Highlights: • Acute and subacute toxicity studies of lutein-PLGA-PL showed no toxicity. • PLGA-PL nanocapsules were safe carriers for oral delivery of lutein. • Oral gavage of lutein-PLGA-PL nanocapsule improves plasma lutein levels.

  12. Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles.

    Science.gov (United States)

    Warheit, D B; Brown, S C; Donner, E M

    2015-10-01

    Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO2) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO2 -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO2 test particles (d50 = 145 nm - 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO2 particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO2 test particles (d50 = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO2 particles (d50 = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD50 for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies - each with different TiO2 particulate-types, demonstrated an absence of

  13. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  14. Acute toxic neuropathy mimicking guillain barre syndrome

    Directory of Open Access Journals (Sweden)

    Muhammed Jasim Abdul Jalal

    2015-01-01

    Full Text Available Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic

  15. Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

    Science.gov (United States)

    Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

    2012-07-01

    A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

  16. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    Directory of Open Access Journals (Sweden)

    Alex Kostianovsky

    2011-06-01

    Full Text Available Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts.

  17. Acute and subacute toxicity of Schinus terebinthifolius bark extract.

    Science.gov (United States)

    Lima, L B; Vasconcelos, C F B; Maranhão, H M L; Leite, V R; Ferreira, P A; Andrade, B A; Araújo, E L; Xavier, H S; Lafayette, S S L; Wanderley, A G

    2009-12-10

    Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases. The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes. For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n=5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n=13/group/sex), for 45 consecutive days. In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance. The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.

  18. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    Science.gov (United States)

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    Science.gov (United States)

    2012-07-23

    ... vivo acute dermal systemic toxicity tests. Corresponding acute oral LD 50 data for the same compounds....), estimated LD 50 , and incidence of death and other adverse effects. Background Information on ICCVAM and... tests. DATES: Nominations and test method data for the acute dermal and oral tests should be submitted...

  20. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  1. Oral toxicity of fipronil insecticide against the stingless bee Melipona scutellaris (Latreille, 1811).

    Science.gov (United States)

    Lourenço, Clara Tavares; Carvalho, Stephan Malfitano; Malaspina, Osmar; Nocelli, Roberta Cornélio Ferreira

    2012-10-01

    For a better evaluation of the model using Apis mellifera in toxicology studies with insecticides, the oral acute toxicity of the insecticide fipronil against the stingless bee Melipona scutellaris was determined. The results showed that fipronil was highly toxic to M. scutellaris, with a calculated LC(50) (48 h) value of 0.011 ng a.i./μL of sucrose solution and an estimated oral LD(50) (48 h) of 0.6 ng a.i./bee. Our results showed that M. scutellaris bee is more sensitive to fipronil than the model specie A. mellifera.

  2. Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

    Directory of Open Access Journals (Sweden)

    Talib Hussain

    2012-04-01

    Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

  3. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    International Nuclear Information System (INIS)

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-01-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted

  4. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    Directory of Open Access Journals (Sweden)

    Ramaswamy Ramaswamy

    2012-10-01

    Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

  5. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

    Science.gov (United States)

    Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

    2014-03-26

    Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

  6. Comparative acute toxicity of shale and petroleum derived distillates.

    Science.gov (United States)

    Clark, C R; Ferguson, P W; Katchen, M A; Dennis, M W; Craig, D K

    1989-12-01

    In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

  7. Acute and sub-acute toxicity of Pithecellobium dulce (Roxb. Benth. stem bark hydroalcoholic extract on Wistar rats

    Directory of Open Access Journals (Sweden)

    Gérard A. Toudji

    2017-10-01

    Full Text Available Context: Pithecellobium dulce (PD is an annual herbaceous plant commonly used in African traditional medicine as a purgative, antipyretic, anti-ulcer and wound dressing agent. Aims: To evaluate the acute and sub-acute toxicity of P. dulce stem bark hydroethanolic extract in Wistar rats. Methods: In the acute test, a single dose of 5 g/kg body weight was administered to Wistar rats afterwards they were observed individually 4 hours post-dosing, and at least once daily for 14 consecutive days. The sub-acute toxicity was evaluated by daily oral administration of 0.5 and 1 g/kg extract, for 28 days. Biochemical and hematological parameters assessment as well as body and organ weights of the rats were carried out. Results: The limit dose of 5 g/kg did not cause any mortality or signs of acute toxicity on the rats during the experimentation period. In the sub-acute test, uterus-ovary-trompe (UOT weight decreased dose-dependently: Control group (0.82 ± 0.03 g; Extract 0.5 g/kg (0.57 ± 0.06 g; Extract 1g/kg (0.48 ± 0.01 g (p ˂ 0.01. Extract lowered urea values in female group treated with 1 g/kg (p < 0.01. Lymphocytes percentage was dose dependently increased in treated male groups: Control group (53.00 ± 0.58%; extract 0.5 g/kg (58.67 ± 0.67% and extract 1 g/kg (60.67 ± 2.41%. Conclusions: These findings suggest that PD is relatively safe when administered orally in rats but is slightly atrophic for female reproductive organs.

  8. Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

    Science.gov (United States)

    Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

    2014-03-01

    In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

  9. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

    Directory of Open Access Journals (Sweden)

    Ayman Goudah

    2015-05-01

    Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  10. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

    Science.gov (United States)

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A

    2015-05-01

    The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  11. Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

    Science.gov (United States)

    Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

  12. Sub-acute toxicity evaluation of ethanol extract of rheumatic tea ...

    African Journals Online (AJOL)

    Sub-acute toxicity profile of Rheumatic Tea Formula (RTF), a polyherbal tea consisting of Salix alba, Eucalyptus globulus and Albizia chevalieri was investigated in wistar rats of both sexes. Wistar rats were orally administered three different doses of ethanol extract of RTF for 28 days after which the effect on body weight, ...

  13. Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

    Science.gov (United States)

    Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

    2014-10-01

    This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

  14. Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

    Science.gov (United States)

    Şeremet, Oana Cristina; Bărbuceanu, Florica; Ionică, Floriana Elvira; Margină, Denisa Marilena; GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Ilie, Mihaela; Gonciar, Veaceslav; Negreş, Simona; ChiriŢă, Cornel

    2016-01-01

    Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

  15. Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats

    Directory of Open Access Journals (Sweden)

    Job Tchoumtchoua

    2014-01-01

    Full Text Available Amphimas pterocarpoides Harms (Leguminosae is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent and without biological relevance indicate a wide margin of safety for the traditional use of AP.

  16. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

    Directory of Open Access Journals (Sweden)

    Glauco Morales

    2014-01-01

    Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti

  17. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  18. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    Differential toxicity and influence of salinity on acute toxicity of copper sulphate and lead nitrate against Oreochromis niloticus. KA Bawa-Allah, F Osuala, J Effiong. Abstract. This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate ...

  19. Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Pixberg, Caroline [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Koch, Raphael [Institute of Biostatistics and Clinical Research, University of Muenster, Muenster (Germany); Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Department of Radiation Oncology, University of Koeln, Koeln (Germany); Martinsson, Ulla [Department of Oncology, University Hospital, Uppsala (Sweden); Kristensen, Ingrid [Department of Radiation Physics, Skåne University Hospital, Lund (Sweden); Matuschek, Christiane [Department of Radiation Oncology, University Hospital of Duesseldorf, Duesseldorf (Germany); Kortmann, Rolf-Dieter [Department of Radiation Oncology, University Hospital of Leipzig, Leipzig (Germany); Pohl, Fabian [Department of Radiation Oncology, University of Regensburg, Regensburg (Germany); Elsayad, Khaled [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Christiansen, Hans [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Willich, Normann [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Lindh, Jack [Department of Radiation Sciences, Umeå University, Umeå (Sweden); Steinmann, Diana [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

    2016-03-15

    Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute

  20. Acute toxicity of ingested fluoride.

    Science.gov (United States)

    Whitford, Gary Milton

    2011-01-01

    This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve. Copyright © 2011 S. Karger AG, Basel.

  1. Acute Toxicity and Cytotoxicity of Pereskia aculeata, a Highly Nutritious Cactaceae Plant.

    Science.gov (United States)

    Silva, Debora O; Seifert, Mauricio; Nora, Fabiana R; Bobrowski, Vera L; Freitag, Rogerio A; Kucera, Heidi R; Nora, Leonardo; Gaikwad, Nilesh W

    2017-04-01

    Pereskia aculeata is a Cactaceae plant with valuable nutritional properties, including terrific amounts of protein, minerals, vitamins, and fiber. However, P. aculeata is reported to contain antinutrients and alkaloids in its leaves. In addition, in a study on growth and development, Wistar rats fed with P. aculeata and casein as protein source grew less than the control group (fed with casein only). Therefore, in this study, we evaluated, for the first time, the oral acute toxicity of P. aculeata in rats and also the cytotoxicity behavior of the plant on lettuce seeds. The acute toxicity research was carried out using dried P. aculeata ethanolic extract, in three different doses, administered by gavage to 24 female Wistar rats. The rats were then examined for signs of toxicity, food intake, body weight, and fecal excretion fluctuations, as well as histopathological alterations, using eight different body tissues. The acute toxicity study did not show any difference among the groups in either clinical evaluation or histopathological analyses. For the cytotoxicity study, dried P. aculeata ethanolic extract was applied on lettuce seeds in five different concentrations. These seeds were evaluated for germination, root and shoot length, and mitotic index. The results show that P. aculeata extract affects lettuce root and shoot growth, but not germination or mitotic index. In conclusion, the acute toxicity on rats and the cytogenotoxicity on lettuce of P. aculeata are neglectable, validating the potential of this plant to be used as a functional food.

  2. Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of “Zapote” Pouteria mammosa (L. Cronquist

    Directory of Open Access Journals (Sweden)

    Carlos M. S. Dutok

    2015-01-01

    Full Text Available The common use of Pouteria mammosa (L. Cronquist, “Mamey or Zapote,” in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25% Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD. The aqueous extract was located in the following category: not classified as toxic (CTA 5, while hydroalcoholic extract at 25% was classified as dangerous (CTA 4. Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating.

  3. Oral cadmium chloride intoxication in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B; Svendsen, P

    1988-01-01

    Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect...

  4. Computerized tomography in acute toxic encephalopathy

    International Nuclear Information System (INIS)

    Aoki, Nobuhiko; Kaneshi, Kunio; Mizuguchi, Masashi; Kurihara, Eiji.

    1983-01-01

    We experienced three cases of acute toxic encephalopathy, including a case of probable Reye syndrome, which had similar and unique CT findings in their acute stage; symmetrical low density area in the thalamus and the dentate nucleus, followed by changes in cerebellar hemispheres and around lateral ventricles. The CT findings, common to probable Reye syndrome and other acute toxic encephalopathy, may suggest the possibility of similar pathogenesis of brain damage in both disorders. The authors propose that present cases are a new subgroup in acute toxic encephalopathy, because of their similar and unique CT features. (author)

  5. Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotectio

    Directory of Open Access Journals (Sweden)

    Mustak Sayyad

    2017-02-01

    Full Text Available Swietenia macrophylla (SM is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

  6. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models

    International Nuclear Information System (INIS)

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q.; Chen, Wei

    2016-01-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD_5_0 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS. - Highlights: • The acute and subchronic toxicity of PFOS was systematically investigated. • The acute oral LD_5_0 value for PFOS in C57BL/6J mice was 0.579 g/kg body weight. • PFOS disrupted the homeostasis of antioxidative systems. • PFOS induced hepatocellular apoptosis and triggered liver injury. - PFOS disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis, and triggered liver injury.

  7. Acute And Toxicity Effect of The Aqueous Extract

    African Journals Online (AJOL)

    Administrator

    antidiarrhoeal, antimalarial and antitrypanosomal activities of plants-based products support this ... Experimental design for Acute toxicity Study: The acute toxicity study was .... Lorke, D. (1983). A new approach to practical acute toxicity testing.

  8. Tomotherapy for prostate adenocarcinoma: A report on acute toxicity

    International Nuclear Information System (INIS)

    Keiler, Louis; Dobbins, Donald; Kulasekere, Ravi; Einstein, Douglas

    2007-01-01

    Background and purpose: To analyze the impact of Tomotherapy (TOMO) intensity modulated radiotherapy (IMRT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer. Materials and methods: The records of 55 consecutively treated TOMO patients were reviewed. Additionally a well-matched group of 43 patients treated with LINAC-based step and shoot IMRT (LINAC) was identified. Acute toxicity was scored according to Radiation Therapy Oncology Group acute toxicity criterion. Results: The grade 2-3 acute GU toxicity rates for the TOMO vs. LINAC groups were 51% vs. 28% (p = 0.001). Acute grade 2 GI toxicity was 25% vs. 40% (p = 0.024), with no grade 3 GI toxicity in either group. In univariate analysis, androgen deprivation, prostate volume, pre-treatment urinary toxicity, and prostate dose homogeneity correlated with acute GI and GU toxicity. With multivariate analysis use of Tomotherapy, median bladder dose and bladder dose homogeneity remained significantly correlated with GU toxicity. Conclusions: Acute GI toxicity for prostate cancer is improved with Tomotherapy at a cost of increased acute GU toxicity possibly due to differences in bladder and prostate dose distribution

  9. Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

    Science.gov (United States)

    Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

    2006-10-01

    An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

  10. Toxicidad aguda oral de la o-vainillina Acute oral toxicity of o-vanillin

    Directory of Open Access Journals (Sweden)

    Yamisleydi Alonso Moreno

    2008-04-01

    Full Text Available El 2-hidroxi-3-metoxibenzaldehído (o-vainillina posee una probada actividad anti sickling y una baja actividad hemolítica sobre hematíes SS y normales, por lo que puede ser eficaz en el tratamiento de la anemia drepanocítica, enfermedad genética de alta prevalencia a nivel global. En este sentido se desarrolló un estudio de toxicidad aguda oral, con el objetivo de determinar sus efectos adversos. Se administró una dosis de 2 000 mg/kg de peso corporal a un grupo de ratas (3 hembras y 3 machos y el vehículo a otro grupo utilizado como control. Los animales se mantuvieron en observación durante 14 días, se determinaron las variaciones de peso, la presencia o no de síntomas y signos clínicos, y la necropsia al finalizar el estudio. Como resultado no se observó disminución del peso corporal en ninguno de los grupos experimentales, presentaron síntomas como: piloerección, respiración acelerada, actividad disminuida, acicalamiento, aislamiento a la esquina de la caja y la muerte de un animal. El análisis macroscópico de los órganos no detectó variación alguna. La DL50 de la o-vainillina se encuentra por encima de 2 000 mg/kg de peso corporal, según el sistema global armonizado2-hydroxy-3-methoxybenzaldehyde (o-vanillin has a proven anitsickling activity and a low haemolytic activity on SS and normal red corpuscles, so it may be efficient in the treatment of drepanocytic anemia, a genetic disease of high prevalence at the world level. In this sense, an acute oral toxicity study was conducted aimed at determining its adverse effects. A dose of 2 000 mg/kg of body weight was administered to a group of rats (3 females and 3 males, where the vehicle was given to the control group. The animals were observed for 14 days. The variations of weight, the presence or not of symptoms and clinical signs, and the necropsy at the end of the study were determined. Body weight reduction was not observed in any of the experimental groups. They

  11. Study on acute toxicity of anti-vertigo granule on mice

    Science.gov (United States)

    Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

    2018-04-01

    To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

  12. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal...... useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall...... obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

  13. Acute toxicity and genotoxicity study of fermented traditional herb formula Guibi-tang.

    Science.gov (United States)

    Park, Hwayong; Hwang, Youn-Hwan; Yang, Hye Jin; Kim, Hyun-Kyu; Song, Kyung Seuk; Ma, Jin Yeul

    2014-10-28

    Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in East Asia. Although this medicine has been widely used, there is little available information on the safety and toxicity of Guibi-tang, especially on the fermented one. Guibi-tang, composed of 12 herbs, was fermented with bacteria and lyophilized. Single dose acute toxicity in rats was observed for 14 days after administration. Genetic toxicity of fermented Guibi-tang was evaluated on bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster ovary cells, and micronucleus formation in mice. Ingredients in FGBT were identified and quantified by high performance liquid chromatography-mass spectrometry. In acute oral toxicity study, behavior, clinical signs and body weight changes were normal observing in all experimental animals. No revertant colonies were found in any bacterial cultures examined. Morphological or numerical anomalies and significant increased number of aberrant metaphases were not observed. Micronucleus assay showed no significant increases in the frequency of inducing micronuclei in any dose examined. Decursinol, decursin, glycyrrhizin, and 6-gingerol in fermented Guibi-tang were identified and quantitated. As a whole, no acute and genotoxic effects were found in all the assays and parameters analyzed. Fermented Guibi-tang was recognized as safe and non-toxic, and therefore can be used for applications of traditional medicine in modern complementary and alternative therapeutics and health care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  15. Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

    Science.gov (United States)

    Oliveira, Alisson Macário de; Nascimento, Matheus Ferreira do; Ferreira, Magda Rhayanny Assunção; Moura, Danielle Feijó de; Souza, Talita Giselly Dos Santos; Silva, Gabriela Cavalcante da; Ramos, Eduardo Henrique da Silva; Paiva, Patrícia Maria Guedes; Medeiros, Paloma Lys de; Silva, Teresinha Gonçalves da; Soares, Luiz Alberto Lira; Chagas, Cristiano Aparecido; Souza, Ivone Antônia de; Napoleão, Thiago Henrique

    2016-12-24

    Morus alba L. (white mulberry) is used in traditional medicine worldwide, including Brazil. The leaves of this plant are used to treat inflammatory disorders. Universal interest in this plant necessitates studies on the toxicological safety and scientific substantiation of the medicinal properties of M. alba. In previous work, we investigated the acute toxicity of orally administered M. alba ethanol extract in mice. This work was designed to investigate the ethanol extract obtained from M. alba leaves for acute toxicity when intraperitoneally administered, in vivo genotoxicity, and potential to reduce acute inflammation. In order to further investigate the constituents of the extract, we also obtained the high-performance liquid chromatography (HPLC) fingerprint of the extract. Phytochemical analysis by thin layer chromatography (TLC) was performed and the results were used to obtain the HPLC fingerprint. Acute toxicity of 300 and 2000mg/kg b.w. i.p. doses administered to mice for 14 days was evaluated. Genotoxicity was evaluated by counting the number of micronucleated polychromatic erythrocytes in the blood of mice that either received or did not receive the extract at 75, 150 and 300mg/kg b.w. per os. The anti-inflammatory effect of the same doses administered per os was investigated using the carrageenan air pouch model. The TLC analysis of the extract revealed the presence of a remarkable amount of flavonoids and cinnamic acids. The HPLC fingerprint showed the presence of one major peak corresponding to chlorogenic acid and two smaller peaks corresponding to flavonoids. In the toxicity assays, there were no deaths or deviations in behavior of treated mice as compared to the control at any dose. However, biochemical, hematological, and histological analyses showed that intraperitoneal injection caused several forms of damage to the mice, which were not observed in case of oral administration, studied in our previous work. Oral administration of the extract did

  16. Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

    Science.gov (United States)

    Nendza, Monika; Müller, Martin; Wenzel, Andrea

    2017-03-22

    Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

  17. Potential fluoride toxicity from oral medicaments: A review.

    Science.gov (United States)

    Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

    2017-08-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  18. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    Science.gov (United States)

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Potential fluoride toxicity from oral medicaments: A review

    Directory of Open Access Journals (Sweden)

    Rizwan Ullah

    2017-08-01

    Full Text Available The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

  20. Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

    Directory of Open Access Journals (Sweden)

    Kanjana Jaijoy

    2007-03-01

    Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

  1. Acute and subchronic toxicity study of the water extract from root of Imperata cylindrica (Linn. Raeusch. in rats

    Directory of Open Access Journals (Sweden)

    Siharat Chunlaratthanaphorn

    2007-03-01

    Full Text Available The water extract from root of Imperata cylindrica (Linn. Raeusch. was studied for acute and subchronic toxicities. The extract at a single dose of 5,000 mg/kg was administered orally to female and male rats (5 male, 5 female. After 14 days, signs and behavioral changes, mortality, gross and histopathological changes of internal organs were examined. The extract did not produce signs of toxicity. For the subchronic toxicity test, the extract at doses of 300, 600 and 1,200 mg/kg body weight was orally administered to rats daily for 90 days (10 male, 10 female. The observation of signs, behavior and health status showed no abnormality in the test groups as compared with the controls. At the end of the study, necropsy and histopathology examination were performed in all animals in the control group, the test groups and the satellite group in which the extract was discontinued for another 28 days. Body and organ weights, hematological and blood clinical chemistry were also examined. The results suggest that the water extract of Imperata cylindrica (Linn. Raeusch does not cause acute and subchronic toxicities in rats.

  2. Oral Chromium Exposure and Toxicity

    Science.gov (United States)

    Sun, Hong; Brocato, Jason

    2015-01-01

    Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

  3. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  4. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening results indicate the presence of saponins, flavonoids, phytosterols and phenols. Acute toxicity study showed there was no mortality at 8000 mg/kg of the extract. The results indicate that the plant is rich in phytochemicals and is relatively safe. Key words: Phytochemicals, acute toxicity, proximate ...

  5. Evaluación de la toxicidad aguda oral e irritación sobre mucosa bucal de la solución CM-95 tratada magnéticamente Oral acute toxicity and irritation on buccal mucosa evaluation of the CM-95 solution magnetically treated

    Directory of Open Access Journals (Sweden)

    Jorge Díaz Bestard

    2008-12-01

    Full Text Available La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993

  6. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

    Science.gov (United States)

    Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

    2013-03-01

    The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Preparation of five 3-MCPD fatty acid esters, and the effects of their chemical structures on acute oral toxicity in Swiss mice.

    Science.gov (United States)

    Liu, Man; Liu, Jie; Wu, Yizhen; Gao, Boyan; Wu, Pingping; Shi, Haiming; Sun, Xiangjun; Huang, Haiqiu; Wang, Thomas Ty; Yu, Liangli Lucy

    2017-02-01

    3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg -1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3-MCPDEs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Albendazole Induced Recurrent Acute Toxic Hepatitis: A Case Report.

    Science.gov (United States)

    Bilgic, Yilmaz; Yilmaz, Cengiz; Cagin, Yasir Furkan; Atayan, Yahya; Karadag, Nese; Harputluoglu, Murat Muhsin Muhip

    2017-01-01

    Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice. For diagnosis, other acute hepatitis etiologies were excluded. Roussel Uclaf Causality Assessment Method (RUCAM) score was calculated and found to be 10, which meant highly probable drug hepatotoxicity. Within 2 months, all pathological findings came to normal. There are a few reported cases of albendazole induced toxic hepatitis, but at adults, there is no known recurrent acute toxic hepatitis due to albendazole at this certainty according to RUCAM score. Physicians should be aware of this rare and potentially fatal adverse effect of albendazole. © Acta Gastro-Enterologica Belgica.

  9. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Ong YS

    2016-11-01

    Full Text Available Yong Sze Ong,1 Latifah Saiful Yazan,1,2 Wei Keat Ng,1 Mustapha M Noordin,3 Sarah Sapuan,1 Jhi Biau Foo,1 Yin Sim Tor1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, 3Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Background: Thymoquinone (TQ, the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods: The in vivo toxicity (acute and subacute toxicity study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ

  10. Potential fluoride toxicity from oral medicaments: A review

    OpenAIRE

    Rizwan Ullah; Muhammad Sohail Zafar; Nazish Shahani

    2017-01-01

    The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, tox...

  11. Toxicity of oral radiotherapy in patients with acquired immunodeficiency syndrome

    International Nuclear Information System (INIS)

    Cooper, J.S.; Fried, P.R.

    1987-01-01

    Although radiotherapy is a standard form of management of head and neck tumors, treatment of the oral cavity in patients who have the acquired immunodeficiency syndrome has produced unacceptable toxicity. Five such patients are described as a warning of enhanced toxicity of oral radiotherapy in this patient population

  12. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    International Nuclear Information System (INIS)

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-01-01

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO 2 and by observing the disappearance of test substance with gas chromatography. Additional BOD 5 and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population

  13. Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

    Directory of Open Access Journals (Sweden)

    Pongri Adarki

    2017-09-01

    Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

  14. Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone, and Itaconic Acid

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    Liwei Tan

    2013-01-01

    Full Text Available A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol-poly(caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA, poly(ethylene glycol methyl ether methacrylate (MPEGMA, MEG, N,N-methylenebisacrylamide (BIS, and itaconic acid (IA were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by 1H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system.

  15. Acute and subacute toxicity of 18F-FDG

    International Nuclear Information System (INIS)

    Dantas, Danielle Maia

    2013-01-01

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18 F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18 F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  16. Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice

    Science.gov (United States)

    Kalantari, Heibatullah; Salimi, Anayatollah; Rezaie, Anahita; Jazayeri Shushtari, Fereshteh; Goudarzi, Mehdi

    2015-01-01

    Background: The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. Objectives: The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Materials and Methods: Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. Results: The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0

  17. Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

    African Journals Online (AJOL)

    Erah

    2010-10-21

    Oct 21, 2010 ... Histopathological assessment of liver sections of treated-rats showed normal ... Keywords: Alchornea cordifolia, Rats, Subacute oral toxicity, Neutrophils, Hepatocytes, Hydropic ..... albino rats against acetaminophen-induced.

  18. Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

    Science.gov (United States)

    de Lima, Rachel; Guex, Camille Gaube; da Silva, Andreia Regina Haas; Lhamas, Cibele Lima; Dos Santos Moreira, Karen Luise; Casoti, Rosana; Dornelles, Rafaela Castro; Marques da Rocha, Maria Izabel Ugalde; da Veiga, Marcelo Leite; de Freitas Bauermann, Liliane; Manfron, Melânia Palermo

    2018-05-14

    Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo ou erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200mg/kg and 400mg/kg of the extract. The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats. Copyright © 2018. Published by Elsevier B.V.

  19. Oral microbiota species in acute apical endodontic abscesses

    OpenAIRE

    Noelle George; Erin Flamiatos; Kellie Kawasaki; Namgu Kim; Charles Carriere; Brian Phan; Raphael Joseph; Shay Strauss; Richie Kohli; Dongseok Choi; J. Craig Baumgartner; Christine Sedgley; Tom Maier; Curtis A. Machida

    2016-01-01

    Background and objectives: Acute apical abscesses are serious endodontic diseases resulting from pulpal infection with opportunistic oral microorganisms. The objective of this study was to identify and compare the oral microbiota in patients (N=18) exhibiting acute apical abscesses, originating from the demographic region in Portland, Oregon. The study hypothesis is that abscesses obtained from this demographic region may contain unique microorganisms not identified in specimens from other re...

  20. Predictive acute toxicity tests with pesticides.

    Science.gov (United States)

    Brown, V K

    1983-01-01

    By definition pesticides are biocidal products and this implies a probability that pesticides may be acutely toxic to species other than the designated target species. The ways in which pesticides are manufactured, formulated, packaged, distributed and used necessitates a potential for the exposure of non-target species although the technology exists to minimize adventitious exposure. The occurrence of deliberate exposure of non-target species due to the misuse of pesticides is known to happen. The array of predictive acute toxicity tests carried out on pesticides and involving the use of laboratory animals can be justified as providing data on which hazard assessment can be based. This paper addresses the justification and rationale of this statement.

  1. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

  2. Acute Toxicity of Tributyltins and Tributyltin Leachates from Marine Antibiofouling Paints.

    Science.gov (United States)

    1982-09-10

    RO-0184 224 ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN i/I LEACHATES FROM MARINE ANTIBIOFOULING PAINTS(U) CALIFORNIA UNIV OAKLAND NAVAL...Classification) (U) ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN LEACHATES FROM MARINE ANTIBIOFOULING PAINTS 12, PERSO A UHR Laugin, Koy"., Linden, Olof and...xins causing acute toxicity or two amphipou species at concentrations as low as 10 g/L . Orchestia traskiana was exposed to bis ( tributyltin ) oxide

  3. Acute Toxic Myocarditis and Pulmonary Oedema Developing from Scorpion Sting

    Directory of Open Access Journals (Sweden)

    Cem Sahin

    2015-03-01

    Full Text Available The majority of scorpion stings are generally seen with a set of simple clinical findings, such as pain, oedema, numbness, and tenderness in the area of the sting. However, occasionally events, such as toxic myocarditis, acute heart failure, acute pulmonary oedema, and Acute Respiratory Distress Syndrome (ARDS, which occur in scorpion sting cases are a significant problem which determine mortality and morbidity. The case presented here was a 38-year-old man who developed acute toxic myocarditis, acute heart failure, and acute pulmonary oedema following a scorpion sting on the 3rd finger of his right hand.

  4. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  5. N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

    Science.gov (United States)

    Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

    2016-01-01

    Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

  6. Antioxidant activity and acute toxicity of Neoglaziovia variegata ...

    African Journals Online (AJOL)

    The total phenolics content of the extracts was determined by the Folin-Ciocalteu method. Total flavonoid was also determined. The most ... of low toxicity. Keywords: Antioxidant activity, acute toxicity, Neoglaziovia variegata, Bromeliaceae ...

  7. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement

    NARCIS (Netherlands)

    Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Sottocornola, Lara; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Paganelli, Corrado; Majorana, Alessandra; Gastaldi, Giorgio; Bossi, Paolo; Berruti, Alfredo; Pavanato, Giovanni; Nicolai, Piero; Maroldi, Roberto; Barasch, Andrei; Russi, Elvio G.; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M.

    2016-01-01

    Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis,

  8. ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ...

    African Journals Online (AJOL)

    ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ETHANOL EXTRACT OF JATROPHA CURCAS SEEDS IN EXPERIMENTAL ANIMALS. ... with the aim of investigating the toxicity of the ethanol seed extract of JC in rats, mice, and chicks; and also to use conventional antidotes to treat intoxication in rats due to ...

  9. Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

    International Nuclear Information System (INIS)

    Sato, Atsushi; Imaizumi, Masue; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Iinuma, Kazuie; Minegishi, Masayoshi

    2006-01-01

    Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

  10. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    Science.gov (United States)

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  11. Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

    Science.gov (United States)

    Nghonjuyi, Ndaleh Wozerou; Tiambo, Christian Keambou; Taïwe, Germain Sotoing; Toukala, Jean Paul; Lisita, Frederico; Juliano, Raquel Soares; Kimbi, Helen Kuokuo

    2016-02-03

    Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low

  12. Evaluación de la toxicidad aguda oral y de la actividad antimicrobiana de una mezcla de aceite de hígado de tiburones de Cuba Assessment of the oral acute toxicity and the antimicrobial activity of an oily mixture from shark's liver of Cuba

    Directory of Open Access Journals (Sweden)

    Caridad Margarita García Peña

    2010-09-01

    Full Text Available Se evaluó la toxicidad aguda oral y la actividad antimicrobiana de una mezcla de aceites de hígado de tiburón, de las especies Rhincodon typu (tiburón ballena y Galeocerdo cuvier (tiburón tigre, que habitan en zonas aledañas a las costas del litoral norte occidental de Cuba, para su posterior uso farmacéutico, debido a que presenta un alto contenido de vitaminas y de ácidos grasos, que le confieren actividad antioxidante y antiinflamatoria. El estudio de la toxicidad aguda oral demostró que la mezcla de aceites de hígado de tiburones, no provocó alteraciones macroscópicas en los órganos extraídos, ni síntomas tóxicos severos, ni mortalidad de ninguno de los animales empleados en el estudio a la dosis de 20 mL/kg. Los resultados del estudio de la actividad antimicrobiana demostraron una ligera actividad bacteriostática frente a K. pneumoniae; además una actividad antifúngica frente a Microsporum canis; y resistencia frente a C. albicans y T. mentagrophytes a las concentraciones evaluadas.The total acute toxicity and the antimicrobial activity of an oil mixtures from shark liver of Rhicodon typu (whale-shark and Galeocerdo cuvier (tigger-shark was assessed in species leaving in the adjacent costs of Cuban northern coastal for its subsequent pharmaceutical use due to its high content of vitamins and fatty acids and its antioxidant and anti-inflammatory activity. Study of oral acute toxicity demonstrated that oil mixture of shark liver hasn't macroscopic alterations in removed organs, severe toxic symptoms and on mortality of any animals used in study at 20 mL/kg dose. Study results of antimicrobial activity showed a slight bacteriostatic activity against K. pneumoniae and an antifungal activity against Microsporum canis, and a resistance against C. albicans and T. mentagrophytes at assessed concentrations.

  13. Subchronic and acute preclinical toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae)

    International Nuclear Information System (INIS)

    Garcia Gonzalez, Mildred; Coto Morales, Teresita; Ocampo, Rafael; Pazos, Liliana

    2006-01-01

    The effects of the aqueous extract of Petiveria alliacea, leaves were tested on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice, of 20 to 25 g mean weight. Treatments were in all cases doses of 1000 and 2000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed in both tests. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1000 mg/kg dose but not for the higher 2000 mg/kg doses. After administering the dose once after a starving period of six hours, no significant differences in intestinal motility could be found. (author) [es

  14. Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae).

    Science.gov (United States)

    García-González, Mildred; Morales, Teresita Coto; Ocampo, Rafael; Pazos, Liliana

    2006-12-01

    We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1,000 and 2,000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1,000 mg/kg dose but not for the higher 2,000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found.

  15. Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

    Science.gov (United States)

    Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

    2018-03-01

    Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

  16. Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment

    International Nuclear Information System (INIS)

    Viani, Gustavo Arruda; Zulliani, Giseli Correa; Stefano, Eduardo Jose; Silva, Lucas Bernardes Godoy da; Silva, Bruna Bueno da; Crempe, Yuri Bonicelli; Martins, Vinicius Spazzapan; Ferrari, Ricardo Jose Rambaiolo; Pólo, Mariana Colbachini; Rossi, Bruno Thiago; Suguikawa, Elton

    2013-01-01

    To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule (C-ARM) with 78 Gy/39 fractions and hypofractionation conformal treatment (H-ARM) with 69 Gy/23 fractions. This prospective double arm study consisted of 217 patients with prostate cancer, 112 in H-ARM and 105 in C-ARM arm. C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions. Weekly assessment of acute reactions was done during treatment and with one, and 3 months using RTOG scale. Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms. Variables with p value less than 0.1 were included in the multivariated logistic regression. There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary (GU) and gastrointestinal (GI) acute toxicity. During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity (grade 0–3; H-ARM = 45.5%, 34%, 18.7% and 1.8% versus C-ARM = 47.6%, 35.2%, 17.2% and 0). For acute GU toxicity no difference was detected between H-ARM (grade 0–3; 22.3%, 54.5%, 18.7% and 4.5%) and C-ARM (grade 0–3; 25.8%, 53.3%, 17.1% and 3.8%). At the 3- months follow-up, persistent Grade > =2 acute GU and GI toxicity were 2.5% and 1.8% in H-ARM versus 5.7% and 3% in C-ARM (p > 0.05). In univariated and multivariated analyses, there was not any dosimetric predictor for GI and GU toxicity. Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer, being well tolerated with minimal severe acute toxicity

  17. Determination of leachate toxicity through acute toxicity using Daphnia pulex and anaerobic toxicity assays

    OpenAIRE

    Carabalí-Rivera, Y. S; Barba-Ho, L. E; Torres-Lozada, P

    2017-01-01

    ABSTRACT The municipal solid waste (MSW) of large cities, in particular the ones of developing countries, is mainly disposed in landfills (LFs), whose inadequate management generates the emission of greenhouse gases and the production of leachates with high concentrations of organic and inorganic matter and, occasionally heavy metals. In this study, the toxicity of the leachates from an intermediate-age municipal landfill was evaluated by ecotoxicity and anaerobic toxicity tests. The acute to...

  18. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

    Science.gov (United States)

    Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

    2018-01-01

    Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

  19. Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti

    OpenAIRE

    Haonan Zhou; Pengjie Zhang; Zhiguo Hou; Jiabin Xie; Yuming Wang; Bin Yang; Yanyan Xu; Yubo Li

    2016-01-01

    Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were availabl...

  20. Acute and Subchronic Toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from Chloroform Bay Leaf Extract (Eugenia Polyantha W.) with Palm Kernel Oil as A Carrier

    Science.gov (United States)

    Prihapsara, F.; Mufidah; Artanti, A. N.; Harini, M.

    2018-03-01

    The present study was aimed to study the acute and subchronic toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with Palm Kernel Oil as carrier. In acute toxicity test, five groups of rat (n=5/groups) were orally treated with Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with doses at 48, 240, 1200 and 6000 mg/kg/day respectively, then the median lethal dose LD50, advers effect and mortality were recorded up to 14 days. Meanwhile, in subchronic toxicity study, 4 groups of rats (n=6/group) received by orally treatment of SNEDDS from chloroform bay leaf extract with doses at 91.75; 183.5; 367 mg/kg/day respectively for 28 days, and biochemical, hematological and histopatological change in tissue such as liver, kidney, and pancreatic were determined. The result show that LD50 is 1045.44 mg/kg. Although histopathological examination of most of the organs exhibited no structural changes, some moderate damage was observed in high‑ dose group animals (367 mg/kg/day). The high dose of SNEDDS extract has shown mild signs of toxicity on organ function test.

  1. Anti-inflammatory activity and sub-acute toxicity of artemetin.

    Science.gov (United States)

    Sertié, J A; Basile, A C; Panizza, S; Matida, A K; Zelnik, R

    1990-02-01

    The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

  2. Safety evaluation of the ethyl acetate extract on irradiated tea parasite: Acute toxicity study on mice

    International Nuclear Information System (INIS)

    Hendig Winarno

    2011-01-01

    Many studies of the pharmacological efficacy of tea parasite and the use of ionizing radiation for decontamination of microbes and extending shelf life have been reported, but there is no information on its safety, such as the acute toxicity. In this study, the acute toxicity of two ethyl acetate extracts from unirradiated and irradiated (irradiation dose of 10 kGy) tea parasites Scurrula atropurpurea on Swiss Webster mice have been examined. The observation was done after the treatment of a single oral dose of ethyl acetate extract in various dose groups, i.e.: control (0 g/kg of mice body weight), D1 (0.625 g/kg), D2 (1.25 g/kg), D3 (2.5 g/kg) D4 (5 g/kg), D5 (10 g/kg) by observing the effect on behavioral response (pharmacological profile), the body weight gains and mortality until the day 14 th . At the last day, the observation of vital organs has also been done. The result showed that no acute toxicity was found in mice treated with a single oral dose of ethyl acetate extract from unirradiated tea parasite and irradiated tea parasite at the dose of 10 kGy. At the dose up to 10 g/kg (equivalent to 77.6 g of extract which administered to human), the normal body weight gains were observed in mice of all dose groups, no mice deaths in any of the dose groups, and no significant change (p > 0.05) in organ weights relative to the body weight i.e.: liver, spleen, kidneys, lung, heart, testes and seminal vesicle (for male), and ovaries and uterus (for female). The approximate lethal doses for male and female mice were determined to be higher than 10 g/kg of mice body weight. It is suggested that the treatment of ethyl acetate extract from unirradiated and irradiated tea parasites until dose up to 10 g/kg of mice body weight was still safe. (author)

  3. Subacute (90 days) oral toxicity studies of Kombucha tea.

    Science.gov (United States)

    Vijayaraghavan, R; Singh, M; Rao, P V; Bhattacharya, R; Kumar, P; Sugendran, K; Kumar, O; Pant, S C; Singh, R

    2000-12-01

    Kombucha tea (KT) is a popular health beverage and is used as an alternative therapy. KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment. The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria. KT is consumed in several countries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments, viz., intestinal disorders, arthritis, ageing and stimulation of immunological system. Though KT is used in several parts of the world its beneficial effects and adverse effects have not been scientifically evaluated. Since there are no animal toxicological data on KT, subacute oral toxicity study was carried out. Five groups of rats were maintained: (a) control group given tap water orally, (b) KT given 2 ml/kg orally, (c) plain tea (PT) given 2 ml/kg orally, (d) KT given in drinking water, 1% (v/v) and (e) PT given in drinking water, 1% (v/v). The rats were given this treatment daily for a period of 90 days. Weekly records of weight, feed intake, water intake and general behaviour were monitored. There was no significant difference in the growth of the animals as evidenced by the progressive body weight change. The organ to body weight ratio and histological evaluation did not show any toxic signs. The haematological and biochemical variables were within the clinical limits. The study indicates that rats fed KT for 90 days showed no toxic effects.

  4. Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

    Science.gov (United States)

    Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

    2013-11-01

    The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

  5. Acute toxicity and associated mechanisms of four strobilurins in algae.

    Science.gov (United States)

    Liu, Xiaoxu; Wang, Yu; Chen, Hao; Zhang, Junli; Wang, Chengju; Li, Xuefeng; Pang, Sen

    2018-04-03

    Strobilurins have been reported highly toxic to non-target aquatic organisms but few illustrated how they cause toxic effects on algae. This study investigated the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly inhibited by all strobilurins, suggesting bc 1 complex might be the target of strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low concentrations of TRI stimulated SOD and POD activities but highest concentration significantly inhibited those activities. Comet assays showed damaged DNA in C. vulgaris by four strobulirins, suggesting their potential genotoxic threats to algae. The results illustrated acute toxicity by strobulirins on algae and their possible toxicity mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Acute oral toxicity test and phytochemistry of some West African medicinal plants.

    Science.gov (United States)

    Awobajo, F O; Omorodion-Osagie, E; Olatunji-Bello, I I; Adegoke, O A; Adeleke, T I

    2009-01-01

    Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. LD50 and phytochemistry of four medicinal plants of West Africa were investigated. Thirty male and non pregnant female Swiss albino mice weighing 20grams each were used for this study. They were divided into the Control (C), Oldenlandia corymbosa L. aqueous leaf-extract treated (OCG), Parquetina nigrescens aqueous leaf extract treated (PNG), Hybanthus enneaspermus aqueous leaf extract treated (HEG), Ficus carica leaf extract treated (FCG) and Sesamum indicum aqueous seeds extract treated group (SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1, 2, 4 and 8, PN; 2.5, 5, 10 and 20, OC; 5, 10, 20 and 40, FC; 1, 2, 4 and 8, HE; 4, 8, 16, 32) of the aqueous extract of each plant (g/kg body weight) after 12 hours fasting. The dry aqueous leaf extracts of HE, OC, PN, FC all have dark brown colour and pH ranging from 6.1 to 7.2 while the seed extract of SI has a light brown color with pH of 7.0. Flavonoids, cardiac glycosides, anthocyanosides, saponin, and reducing sugar were present in all extracts, while cyanogenic glycoside was present only in HE. LD50 determination results obtained using Thompson and Finney methods were as follows; OC; 14.14 +/- 0.27 and 10.56 +/- 0.20, PN; 12.60 +/- 0.10 and 13.10 +/- 0.10, HE; 8.14 +/- 0.30 and 8.24 +/- 0.35, FC; 3.36 +/- 0.26 and 4.00 +/- 0.04, SI; 4.00 +/- 0.10 and 3.10 +/- 0.22 respectively (LD50 values are in g/kg body weight. The results of this study have provided an oral LD50 from where a safe dose can be chosen for further research into the merits of the consumption of these medicinal plants.

  7. Metal and pharmaceutical mixtures: Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?

    Energy Technology Data Exchange (ETDEWEB)

    Alsop, Derek, E-mail: alsopde@mcmaster.ca; Wood, Chris M.

    2013-09-15

    Highlights: •Zebrafish larvae were used to test the acute toxicity of contaminant mixtures. •Interactions were observed between metals, ammonia and pharmaceuticals. •Larval Na{sup +} loss was observed with exposure to all acutely toxic contaminants tested. •Water quality criteria should recognize the toxic interactions between contaminants. -- Abstract: The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4–8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC{sub 50}, one third of the LC{sub 01}) to all copper treatments decreased the copper 96 h LC{sub 50} by 58%, while sublethal copper exposure (6% of the copper LC{sub 50}, 13% of the LC{sub 01}) decreased the cadmium 96 h LC{sub 50} by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na{sup +} followed by K{sup +} (as high as 19% and 9%, respectively, in 24 h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na{sup +} and K{sup +}. Overall, whole body Na{sup +} loss showed the greatest correlation with mortality across a

  8. Metal and pharmaceutical mixtures: Is ion loss the mechanism underlying acute toxicity and widespread additive toxicity in zebrafish?

    International Nuclear Information System (INIS)

    Alsop, Derek; Wood, Chris M.

    2013-01-01

    Highlights: •Zebrafish larvae were used to test the acute toxicity of contaminant mixtures. •Interactions were observed between metals, ammonia and pharmaceuticals. •Larval Na + loss was observed with exposure to all acutely toxic contaminants tested. •Water quality criteria should recognize the toxic interactions between contaminants. -- Abstract: The acute toxicities and mechanisms of action of a variety of environmental contaminants were examined using zebrafish larvae (Danio rerio; 4–8 days post fertilization). Toxic interactions were observed between metals. For example, the addition of a sublethal level of nickel (15% of the LC 50 , one third of the LC 01 ) to all copper treatments decreased the copper 96 h LC 50 by 58%, while sublethal copper exposure (6% of the copper LC 50 , 13% of the LC 01 ) decreased the cadmium 96 h LC 50 by 47%. Two predictive models were assessed, the concentration addition (CA) model, which assumes similar mechanisms of action, and the independent action (IA) model, which assumes different mechanisms of action. Quantitative comparisons indicated the CA model performed better than the IA model; the latter tended to underestimate combined toxicity to a greater extent. The effects of mixtures with nickel or ammonia were typically additive, while mixtures with copper or cadmium were typically greater than additive. Larvae exposed to cadmium, copper or nickel experienced whole body ion loss. Decreases were greatest for Na + followed by K + (as high as 19% and 9%, respectively, in 24 h). Additive toxicity between copper and other pharmaceutical compounds such as fluoxetine (Prozac™), β-naphthoflavone, estrogen and 17α-ethinylestradiol were also observed. Similar to metals, acutely toxic concentrations of fluoxetine, β-naphthoflavone and ammonia all decreased whole body Na + and K + . Overall, whole body Na + loss showed the greatest correlation with mortality across a variety of toxicants. We theorize that a disruption of

  9. Toxicity of Pesticides. Agrichemical Fact Sheet 2.

    Science.gov (United States)

    Hock, Winand K.

    This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

  10. Acute and subchronic toxicity studies of the original drug FS-1

    Directory of Open Access Journals (Sweden)

    Assem Kalykova

    2016-01-01

    Full Text Available Interest in iodine complexes has increased significantly in recent years because of their wide spectrum of biological activity. The FS-1 is an ion nanostructured complex formed by proteins and/or polypeptides, carbohydrates, salts of alkali and alkaline earth metals with intercalated iodine. Patented in 2014, it is intended for the treatment of infectious diseases of bacterial origin including nosocomial infections and multidrug resistant tuberculosis. The aim of the study was to determine its acute and subchronic toxicity. The study of acute and subchronic toxicity was performed on adult Wistar rats according to OECD guidelines. The data on acute toxicity showed LD50 > 2,000 mg/kg after a single intragastric administration. Twenty-eight days of FS-1 administration at a dose of 500 mg/kg resulted in toxic effects. At a dose of 250 mg/kg, the toxic effects were temporary and a return to normal followed after the recovery period. Doses of 100 mg/kg had no adverse effects on the rats.

  11. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

    Science.gov (United States)

    Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

    2014-08-01

    The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Acute inhalation toxicity of carbonyl sulfide

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Hahn, F.F.; Barr, E.B. [and others

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  13. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

    Science.gov (United States)

    To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

  14. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    Marc A. Ellsworth

    2014-01-01

    Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

  15. Psychosis associated with acute recreational drug toxicity: a European case series

    OpenAIRE

    Vallersnes, Odd Martin; Dines, Alison M.; Wood, David M.; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Dargan, Paul I.

    2016-01-01

    Background Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. Methods ...

  16. Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

    Science.gov (United States)

    Sertié, J A A; Woisky, R G; Wiezel, G; Rodrigues, M

    2005-05-01

    Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

  17. Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

    Science.gov (United States)

    Davoudi, Bahar

    More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

  18. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Müller, Klaus Gottlob; Mogensen, Signe Sloth

    2017-01-01

    obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically...

  19. Sub-acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Shin Yee Fung

    2016-08-01

    Full Text Available Lignosus also known as Tiger Milk Mushroom, is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500 and 1000 mg/kg to the SD rats once daily, consecutively for 28 days. Body weight of the rats was recorded and general behavior, adverse effects and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL dose is more than 1000 mg/kg.

  20. Toxicity of Single and Mixed Contaminants in Seawater Measured with Acute Toxicity Bioassays

    Directory of Open Access Journals (Sweden)

    A.R. Fernandez-Alba

    2002-01-01

    Full Text Available Different types of organic pollutants commonly detected in seawater have been evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and Selenastrum capricornotum were selected to test toxic effects of individual compounds and mixtures of these compounds, obtaining EC50 values in the range of 0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were seen for a clear majority of the cases (>60%. Mixtures containing methyl-tertiary-butyl ether (MTBE exhibit accelerated processes that result in a change in concentration required to produce a toxic effect; for example, in the case of mixtures containing MTBE and Diuron and Dichlofluanid.

  1. Acute and chronic arsenic toxicity

    OpenAIRE

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

  2. Acute Toxicity in Definitive Versus Postprostatectomy Image-Guided Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Cheng, Jonathan C.; Schultheiss, Timothy E.; Nguyen, Khanh H.; Wong, Jeffrey Y.C.

    2008-01-01

    Purpose: To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. Methods and Materials: Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving ≥45, ≥65, and ≥70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. Results: A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. Conclusion: The results of our

  3. Acute and subacute toxicity of 18F-FDG

    International Nuclear Information System (INIS)

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A.

    2013-01-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the 18 F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  4. Acute toxicity of tobacco ( Nicotiana tobaccum ) leaf dust on ...

    African Journals Online (AJOL)

    Experiments were conducted using dry tobacco (Nicotiana tobaccum) leaves aqueous extract to determine the acute toxicity and sub lethal effects on some haematological indices of Oreochromis niloticus using static renewable bioassay method. The extract was found to be toxic with a 48-h LC50 value of 109.6 mg/l.

  5. Acute Toxicity of a Recently Identified Phenol-based Synthetic ...

    African Journals Online (AJOL)

    This paper reports on the acute toxicity of a new phenol based synthetic tsetse fly repellent recently identified at the International Centre for Insect Physiology and Ecology (patent No. ... The repellent can be classified as being highly toxic with central nervous system (CNS) involvement and a mild skin and eye irritant.

  6. Acute toxicity of Headline® fungicide to Blanchard's cricket frogs (Acris blanchardi).

    Science.gov (United States)

    Cusaac, J Patrick W; Morrison, Shane A; Belden, Jason B; Smith, Loren M; McMurry, Scott T

    2016-04-01

    Previous laboratory studies have suggested that pyraclostrobin-containing fungicide formulations are toxic to amphibians at environmentally relevant concentrations. However, it is unknown if all pyraclostrobin formulations have similar toxicity and if toxicity occurs in different amphibian species. We investigated the acute toxicity of two formulations, Headline(®) fungicide and Headline AMP(®) fungicide, to Blanchard's cricket frogs (Acris blanchardi) based on a direct overspray scenario. In addition, we examined body residues of fungicide active ingredients in A. blanchardi following direct exposure to Headline AMP fungicide. Headline fungicide and Headline AMP fungicide had similar toxicity to A. blanchardi with calculated median lethal doses of 2.1 and 1.7 µg pyraclostrobin/cm(2), respectively, which are similar to the suggested maximum label rate in North American corn (2.2 and 1.52 µg pyraclostrobin/cm(2), respectively). Tissue concentrations of pyraclostrobin were lower than predicted based on full uptake of a direct dose, and did not drop during the first 24 h after exposure. Headline fungicides at corn application rates are acutely toxic to cricket frogs, but acute toxicity in the field will depend on worst-case exposure.

  7. Acute Toxicity and the Effect of Andrographolide on Porphyromonas gingivalis-Induced Hyperlipidemia in Rats

    Science.gov (United States)

    Al-Bayaty, Fouad; Al-Obaidi, Mazen M. Jamil; Abdulla, Mahmood A.

    2013-01-01

    The aim of the current study is to evaluate the effect of andrographolide on hyperlipidemia induced by Porphyromonas gingivalis in rats. Thirty male Sprague Dawley (SD) rats were divided into five groups as follows: group 1 (vehicle) and four experimental groups (groups 2, 3, 4, and 5) were challenged orally with P. gingivalis ATCC 33277 (0.2 mL of 1.5 ×1012 bacterial cells/mL in 2% carboxymethylcellulose (CMC) with phosphate-buffered saline (PBS)) five times a week for one month to induce hyperlipidemia. Then, group 3 received a standard oral treatment with simvastatin 100 mg/kg, and groups 4 and 5 received oral treatment with andrographolide 20 mg/kg and 10 mg/kg, respectively, for another month. The results showed that total cholesterol (TC), low-density lipoprotein (LDL-C), and triglycerides (TG) were reduced significantly in groups treated with andrographolide. The malondialdehyde (MDA) level was low in treated groups, while antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly increased in these groups (P andrographolide reduce the accumulation of lipid droplets in hepatic tissue cells. An acute toxicity test did not show any toxicological symptoms in rats. PMID:23844365

  8. The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial

    International Nuclear Information System (INIS)

    Kneebone, Andrew; Mameghan, Hedy; Bolin, Terry; Berry, Martin; Turner, Sandra; Kearsley, John; Graham, Peter; Fisher, Richard; Delaney, Geoff

    2001-01-01

    Purpose: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. Methods and Materials: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. Results: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p=0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p=0.41), consistency (p=0.20), flatus (p=0.25), mucus (p=0.54), and pain (p=0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p=0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p=0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). Conclusion: This study suggests that oral

  9. Acute and chronic toxicity of boron to a variety of freshwater organisms.

    Science.gov (United States)

    Soucek, David J; Dickinson, Amy; Koch, Brian T

    2011-08-01

    Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far. Copyright © 2011 SETAC.

  10. Oral hygiene and mouth care for older people in acute hospitals: part 1.

    Science.gov (United States)

    Steel, Ben J

    2017-10-31

    The oral health of older people in acute hospitals has rarely been studied. Hospital admission provides a prime opportunity for identification and rectification of problems, and oral health promotion. This two-part article explores oral hygiene and mouth care provision for older adults in acute hospitals. The first article presents the findings of a literature review exploring oral and dental disease in older adults, the importance of good oral health and mouth care, and the current situation. Searches of electronic databases and the websites of relevant professional health service bodies in the UK were undertaken to identify articles and guidelines. The literature shows a high prevalence of oro-dental disease in this population, with many known detrimental effects, combined with suboptimal oral hygiene and mouth care provision in acute hospitals. Several guidelines exist, although the emphasis on oral health is weaker than other aspects of hospital care. Older adults admitted to acute hospitals have a high burden of oro-dental disease and oral and mouth care needs, but care provision tends to be suboptimal. The literature is growing, but this area is still relatively neglected. Great potential exists to develop oral and mouth care in this context. The second part of this article explores clinical recommendations. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  11. Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

    African Journals Online (AJOL)

    given orally to male and female rats at doses of 250 mg/kg, 500 mg/kg and 1000 ... There were no significant differences in body weight and organ weight between ... major vital organs (liver, kidney, stomach, spleen, brain and heart) tested.

  12. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

    Directory of Open Access Journals (Sweden)

    Paula Abal

    2017-02-01

    Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

  13. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing

    NARCIS (Netherlands)

    Busquet, F.; Strecker, R.; Rawlings, J.M.; Belanger, S.E.; Braunbeck, T.; Carr, G.J.; Cenijn, P.H.; Fochtman, P.; Gourmelon, A.; Hübler, N.; Kleensang, A.; Knöbel, M.; Kussatz, C.; Legler, J.; Lillicrap, A.; Martínez-Jerónimo, F.; Polleichtner, C.; Rzodeczko, H.; Salinas, E.; Schneider, K.E.; Scholz, S.; van den Brandhof, E.J.; van der Ven, L.T.; Walter-Rohde, S.; Weigt, S.; Witters, H.; Halder, M.

    2014-01-01

    A The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were

  16. Manual and oral apraxia in acute stroke, frequency and influence on functional outcome

    DEFF Research Database (Denmark)

    Pedersen, P M; Jørgensen, H S; Kammersgaard, L P

    2001-01-01

    To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome.......To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome....

  17. Organ specific acute toxicity of the carcinogen trans-4-acetylaminostilbene is not correlated with macromolecular binding.

    Science.gov (United States)

    Pfeifer, A; Neumann, H G

    1986-09-01

    trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic in rats and lesions are produced specifically in the glandular stomach. Toxicity is slightly increased by pretreating the animals with phenobarbital (PB) and is completely prevented by pretreatment with methylcholanthrene (MC). The prostaglandin inhibitors, indomethacin and acetyl salicylic acid, do not reduce toxicity. The high efficiency of MC suggested that toxicity is caused by reactive metabolites. trans-[3H]-AAS was administered orally to untreated and to PB- or MC-pretreated female Wistar rats and target doses in different tissues were measured by means of covalent binding to proteins, RNA and DNA. Macromolecular binding in the target tissue of poisoned animals was significantly lower than in liver and kidney and comparable to other non-target tissues. Pretreatment with MC lowered macromolecular binding in all extrahepatic tissues but not in liver. These findings are not in line with tissue specific metabolic activation. The only unique property of the target tissue, glandular stomach, that we observed was a particular affinity for the systemically available parent compound. In the early phase of poisoning, tissue concentrations were exceedingly high and the stomach function was impaired.

  18. Antitoxic effect of Veratrilla baillonii on the acute toxicity in mice induced by Aconitum brachypodum, one of the genus Aconitum.

    Science.gov (United States)

    Ge, Yue-Bin; Jiang, Yi; Zhou, Huan; Zheng, Mi; Li, Jun; Huang, Xian-Ju; Gao, Yue

    2016-02-17

    Aconitum brachypodum Diels (Family Ranunculaceae) is well known for both its good therapy and high toxicity in Yunnan and Sichuan provinces in China. Noticeably, Veratrilla baillonii Franch (Family Gentianaceae), an ethnodrug used by Naxi and Lisu nationalities in Yunnan Province, has been widely considered to possess antitoxic effects on Aconitum plants in herbal therapy and folklore medicines. The present study was conducted to determine the detoxic activities of the water decoction of Veratrilla baillonii Franch (WVBF) on the the chloroform fraction of Aconitum brachypodum Diels (CFA) induced acute toxicity in mice. The physiological (symptoms, body weight, etc.) as well as pathological and clinical biochemistry parameters were assessed and used as the markers for the toxicity. (1)H nuclear magnetic resonance (NMR) based metabolic approach was adopted to further discuss the mechanism. The acute poisoning effects of CFA on mice were observed at doses of 20-62.5mgkg(-1), resulting in an oral median lethal dose (LD50) of 41.3mgkg(-1). Histologically, distinct degenerative changes of the heart, liver and kidney were observed. The biochemistry parameters in the serum as well as metabolites in heart and brain were also altered. However, WVBF (25-200mg/kg) attenuated all the acute toxicity and pathological changes, properly regulated the biochemistry parameters, and reversed the concentration alterations for some metabolites in the heart and brain of mice induced by 40mg/kg of CFA to a certain extent. WVBF significantly reduced the onset of the CFA toxicity. This study may contribute to further understanding of the toxicological and pharmacological profiles of Aconitum brachypodum and the detoxic property of Veratrilla baillonii. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. A Challenging Case of Acute Mercury Toxicity

    Directory of Open Access Journals (Sweden)

    Ali Nayfeh

    2018-01-01

    Full Text Available Background. Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. Clinical Case. A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Conclusion. Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices.

  20. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  1. Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells.

    Science.gov (United States)

    Liu, Man; Gao, Bo-Yan; Qin, Fang; Wu, Ping-Ping; Shi, Hai-Ming; Luo, Wei; Ma, Ai-Niu; Jiang, Yuan-Rong; Xu, Xue-Bing; Yu, Liang-Li Lucy

    2012-10-01

    The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1-monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined 2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate dose-dependently decreased the mean body weight, and caused significant increase of serum urea nitrogen and creatinine in dead mice compared to the control and survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate were renal tubular necrosis, protein casts and spermatids decrease in the seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50 value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW. Obvious changes were not observed on mean body weight, absolute and relative organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD dipalmitate. However, renal tubular necrosis, protein casts and spermatids decrease were also observed in the dead mice. In addition, MTT and LDH assay results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat kidney cells in a dose-dependent manner. Together, the results indicated a greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti.

    Science.gov (United States)

    Zhou, Haonan; Zhang, Pengjie; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Yang, Bin; Xu, Yanyan; Li, Yubo

    2016-11-25

    Radix Aconiti , a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

  3. Acute toxicity of postoperative IMRT and chemotherapy for endometrial cancer

    International Nuclear Information System (INIS)

    Tierney, R.M.; Powell, M.A.; Mutch, D.G.; Gibb, R.K.; Rader, J.S.; Grigsby, P.W.

    2007-01-01

    The aim of this study was to determine the acute toxicity of postoperative intensity-modulated radiotherapy (IMRT) with and without chemotherapy in patients with endometrial cancer. A total of 19 patients with stages IB-IVB endometrial cancer who underwent surgery and postoperative IMRT were reviewed. The treatment planning goal was to cover the tissue at risk and minimize the dose to the bladder, bowel, and bone marrow. Median dose was 50.4 Gy (range 49.6-51.2 Gy). Altogether, 14 patients underwent chemotherapy; most were given carboplatin and paclitaxel. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). The prescribed radiation treatment was completed in all patients. The prescribed cycles of chemotherapy were completed in all 14 patients, except one who received five of six cycles limited by prolonged thrombocytopenia. Chemotherapy was delayed in two patients (14%). Three patients required growth factor support during chemotherapy, and one patient required a blood transfusion. Acute grades 3-4 hematological toxicity occurred in 9 of the 14 patients (64%) who underwent chemotherapy. None experienced acute grade 3 or 4 genitourinary or gastrointestinal toxicity. Adjuvant IMRT and chemotherapy following surgery in patients with endometrial cancer is well tolerated and did not lead to treatment modification in most patients. (author)

  4. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

    DEFF Research Database (Denmark)

    Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

    2018-01-01

    impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...

  5. Acute toxicity, lipid peroxidation and ameliorative properties of ...

    African Journals Online (AJOL)

    OKEY

    2014-01-29

    Jan 29, 2014 ... Full Length Research Paper. Acute toxicity ... Diabetes mellitus represents a group of metabolic ... Figure 1. Pictorial view of Alstonia boonei leaves (Sidiyasa, 1998). ..... The position of hydroxyl groups and other features in the.

  6. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    Directory of Open Access Journals (Sweden)

    Subramanion L. Jothy

    2013-01-01

    Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

  7. Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats.

    Science.gov (United States)

    Li, I-Chen; Chen, Wan-Ping; Chen, Yen-Po; Lee, Li-Ya; Tsai, Yueh-Ting; Chen, Chin-Chu

    2018-01-23

    This study aimed to establish an in vitro model to confirm the efficacy of erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its potential adverse effects in a preclinical experimental setting, including an assessment on the oral administration of EAHE mycelia in acute and prenatal developmental toxicity tests. At a single dose of 5000 mg/kg body weight, EAHE mycelia elicited no death or treatment-related signs of toxicity in ten Sprague-Dawley rats of both sexes during the 14 days of the experimental period. After considering the recommended dose range of EAHE mycelia from the acute toxicity test as well as the therapeutic doses, EAHE mycelia was administered to 66 pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750, and 2625 mg/kg body weight, respectively. All dams were subjected to a Caesarean section on the 20th day of pregnancy, and the fetuses were examined for any morphological abnormalities. Results indicated that weight of uterus, fetal body weight, number of corpora lutea, implantation sites, pre-implantation loss, and post-implantation loss of the treatment groups and the control group exhibited no statistical difference. In addition, no significant differences were observed in the fetal external, organ, and skeletal examinations. Taken together, it can be concluded that EAHE mycelia is considered safe and practically nontoxic for consumption within the appropriate doses and investigation period in this study.

  8. A comparative assessment of the acute inhalation toxicity of vanadium compounds.

    Science.gov (United States)

    Rajendran, N; Seagrave, J C; Plunkett, L M; MacGregor, J A

    2016-11-01

    Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V 2 O 3 , V 2 O 4 , and V 2 O 5 , which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO 4 (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V 2 O 5 was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO 4 was more toxic than the V 2 O 5 particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.

  9. Comparison of Acute Toxicity of Algal Metabolites Using Bioluminescence Inhibition Assay

    Directory of Open Access Journals (Sweden)

    Hansa Jeswani

    2015-01-01

    Full Text Available Microalgae are reported to degrade hazardous compounds. However, algae, especially cyanobacteria are known to produce secondary metabolites which may be toxic to flora, fauna and human beings. The aim of this study was selection of an appropriate algal culture for biological treatment of biomass gasification wastewater based on acute toxicity considerations. The three algae that were selected were Spirulina sp., Scenedesmus abundans and a fresh water algal consortium. Acute toxicity of the metabolites produced by these algal cultures was tested at the end of log phase using the standard bioluminescence inhibition assay based on Vibrio fischeri NRRLB 11174. Scenedesmus abundans and a fresh water algal consortium dominated by cyanobacteria such as Phormidium, Chroococcus and Oscillatoria did not release much toxic metabolites at the end of log phase and caused only about 20% inhibition in bioluminescence. In comparison, Spirulina sp. released toxic metabolites and caused 50% bioluminescence inhibition at 3/5 times dilution of the culture supernatant (EC50.

  10. Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

    Science.gov (United States)

    Lyoussi, Badiaa; Cherkaoui Tangi, Khadija; Morel, Nicole; Haddad, Mohamed; Quetin-Leclercq, Joelle

    2018-01-01

    The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC 50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD 50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

  11. Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

    Energy Technology Data Exchange (ETDEWEB)

    Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

    2011-10-15

    All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

  12. Acute toxicity of injection of 153Sm-EDTMP

    International Nuclear Information System (INIS)

    Chen Baiwei; Chai Xuehong

    2004-01-01

    Sm-153 has several distinct advantages as a radiopharmaceutical for the treat of patients with bone to skeletal metastasis. Sm-153 shows high skeletal uptake and rapid blood and nonosseous tissue clearance. Several paper have considered the toxicity of 153Sm-EDTMP. We report the acute toxicity in mice and rats after injection of 153Sm-EDTMP or unlabeled EDTMP. The EDTMP was injected to mice by 9.76, 7.8, 6.25, 5, 4 mg/Kg. The logarithmic dose of EDTMP were given to mice to determine LD50. The LD50 of EDTMP in mice is 7.1 mg/Kg. The decay of 153Sm-EDTMP for 4 months were injected to mice at dose of 225 mg/Kg. 153Sm-EDTMP were given at 4 difference dosage to rats by 74 MBq/Kg, 370 MBq/Kg, 1110 MBq/Kg, 1850 MBq/Kg. The LD50 of 153Sm-EDTMP in rats is more than 370 MBq/Kg. Although the cold EDTMP LD50 was low, chelated with Sm can decrease it's toxicity. The decay 153Sm-EDTMP can be safe at dose of 225 mg/Kg. The clinical dose will be used at 37 MBq/Kg. So there is no need to consider to acute toxicity in clinical used 153Sm-EDTMP in designated regimen because the safe range is wide enough to cover clinical used. (authors)

  13. Acute Toxicity and the Effect of Andrographolide on Porphyromonas gingivalis-Induced Hyperlipidemia in Rats

    Directory of Open Access Journals (Sweden)

    Rami Al Batran

    2013-01-01

    Full Text Available The aim of the current study is to evaluate the effect of andrographolide on hyperlipidemia induced by Porphyromonas gingivalis in rats. Thirty male Sprague Dawley (SD rats were divided into five groups as follows: group 1 (vehicle and four experimental groups (groups 2, 3, 4, and 5 were challenged orally with P. gingivalis ATCC 33277 (0.2 mL of bacterial cells/mL in 2% carboxymethylcellulose (CMC with phosphate-buffered saline (PBS five times a week for one month to induce hyperlipidemia. Then, group 3 received a standard oral treatment with simvastatin 100 mg/kg, and groups 4 and 5 received oral treatment with andrographolide 20 mg/kg and 10 mg/kg, respectively, for another month. The results showed that total cholesterol (TC, low-density lipoprotein (LDL-C, and triglycerides (TG were reduced significantly in groups treated with andrographolide. The malondialdehyde (MDA level was low in treated groups, while antioxidant enzymes, superoxide dismutase (SOD, and glutathione peroxidase (GPx were significantly increased in these groups (. Liver tissues of the groups treated with andrographolide reduce the accumulation of lipid droplets in hepatic tissue cells. An acute toxicity test did not show any toxicological symptoms in rats.

  14. Acute toxicity and bio-accumulation of mercury and copper in ...

    African Journals Online (AJOL)

    The acute toxicity of Mercury and Copper on C. africanus and T. fuscatus and the bio-accumulation potentials of the metals were investigated in laboratory experiments employing standard bio–assay techniques. On the basis of LC50 values, both metals had similar magnitudes of toxicity against C. africanus. However ...

  15. Comparison of intramuscular olanzapine, orally disintegrating olanzapine tablets, oral risperidone solution, and intramuscular haloperidol in the management of acute agitation in an acute care psychiatric ward in Taiwan.

    Science.gov (United States)

    Hsu, Wen-Yu; Huang, Si-Sheng; Lee, Bo-Shyan; Chiu, Nan-Ying

    2010-06-01

    The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

  16. Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti

    Directory of Open Access Journals (Sweden)

    Haonan Zhou

    2016-11-01

    Full Text Available Radix Aconiti, a classic traditional Chinese medicine (TCM, has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA. Finally, the CCA results showed that LysoPC(22:5 is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

  17. Acute and subacute toxicity of {sup 18F}-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A., E-mail: danielle_2705@hotmail.com, E-mail: jaossoj@yahoo.com.br, E-mail: ngsilva@ipen.br, E-mail: apaulasp2008@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the {sup 18}F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

  18. Acute and subacute toxicities of defatted ethanolic extract of Moringa ...

    African Journals Online (AJOL)

    Moringa oleifera seeds are widely accepted as a nutritional supplement. The seeds are consumed and are sold on the shelf of nature, herbal shops, pharmacy and supermarkets. They are consumed as herbal remedy for various diseases. This study was designed to evaluate the acute and sub-acute toxicity of defatted ...

  19. Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?

    DEFF Research Database (Denmark)

    Da Silva, Emilie; Sørli, Jorid Birkelund

    2018-01-01

    According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403......, TG 436, and TG 433). Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced....

  20. Protective efficacy of various carbonyl compounds and their metabolites, and nutrients against acute toxicity of some cyanogens in rats: biochemical and physiological studies

    Directory of Open Access Journals (Sweden)

    Bhattacharya Rahul

    2017-09-01

    Full Text Available Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen poisoning. The present study reports the protective efficacy of 14 carbonyl compounds and their metabolites, and nutrients (1.0 g/kg; oral; +5 min against acute oral toxicity of acetonitrile (ATCN, acrylonitrile (ACN, malononitrile (MCN, propionitrile (PCN, sodium nitroprusside (SNP, succinonitrile (SCN, and potassium ferricyanide (PFCN in rats. Maximum protection index was observed for alpha-ketoglutarate (A-KG against MCN and PCN (5.60, followed by dihydroxyacetone (DHA against MCN (2.79. Further, MCN (0.75 LD50 caused significant increase in cyanide concentration in brain, liver and kidney and inhibition of cytochrome c oxidase activity in brain and liver, which favorably responded to A-KG and DHA treatment. Up-regulation of inducible nitric oxide synthase by MCN, PCN and SNP, and uncoupling protein by PCN and SNP observed in the brain was abolished by A-KG administration. However, no DNA damage was detected in the brain. MCN and SNP significantly decreased the mean arterial pressure, heart rate, respiratory rate and neuromuscular transmission, which were resolved by A-KG. The study suggests a beneficial effect of A-KG in the treatment of acute cyanogen poisoning.

  1. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

  2. Evaluation of the acute toxicity of refined petroleum products against ...

    African Journals Online (AJOL)

    Static and static-renewal evaluation of the acute toxicity of three refined petroleum products — petrol, kerosene and diesel — against two freshwater animals, the mollusc Pila ovata and the fish Poecilia reticulata, was conducted in the laboratory. Petrol, kerosene and diesel were found to be moderately toxic to the test ...

  3. Effects of sub acute oral administration of aqueous extract of ...

    African Journals Online (AJOL)

    The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

  4. Acute oral toxicity and cytotoxicological evaluation of the ethanol ...

    African Journals Online (AJOL)

    Lucas Nicolau

    2015-02-02

    Feb 2, 2015 ... Piauí, Brazil. 2Medicinal .... at 24 ± 1°C and 12 h light dark cycle with water and food (FRI-LAB .... (OECD, 2001), acute treatment with distilled water and .... Farm. 2:50-. 53. OECD (Organisation for Economic Co-operation and ...

  5. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  6. Logistic Analysis Of Acute Toxicity Of Hunteria Umbellata Extract In ...

    African Journals Online (AJOL)

    In this paper, we analyse the acute toxicity of Hunteria umbellata, a herbal medicinal plant, in mice in Nigeria using the logistic model. Hunteria umbellata is a plant with therapeutic potentials in the treatment of various diseases that include yaws, peptic ulcers, diabetes, piles, infertility and inflammation. Data on the acute ...

  7. Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

    Science.gov (United States)

    Segal, L; Penman, M G; Piriou, Y

    2018-01-01

    The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

  8. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... period. Chamber concentration may be measured using gravimetric or analytical methods as appropriate. If...) Conventional acute toxicity test—(1) Principle of the test method. Several groups of experimental animals are... practicable, monitored continuously or intermittently depending on the method of analysis, and recorded at...

  9. Phytochemical composition and acute toxicity evaluation of aqueous ...

    African Journals Online (AJOL)

    This study was carried out to determine the phytochemical constituents and acute toxicity of the aqueous root bark extract of Securidaca longipedunculata Linn. The result of phytochemical screening revealed the presence of some secondary metabolites of pharmacological significance in the aqueous root bark extract ...

  10. Oral hygiene care of patients with oral cancer during postoperative irradiation. An alleviating effect on acute radiation mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi [Niigata Univ. (Japan). School of Dentistry; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta

    2000-09-01

    To evaluate the effect of oral hygiene care of patients with oral cancer on alleviating acute radiation mucositis. Eighteen patients receiving postoperative radiotherapy for tongue and oral floor cancer were evaluated. Radiotherapy was given in 2 Gy per fraction, 5 times a week for a total dose of 50 Gy in most patients. Radiation field included the tongue and oral floor. During radiotherapy, 8 patients were treated by dento-maxillofacial radiologists with special concern on oral hygiene (oral hygiene group) and the remaining 10 patients were treated with routine dental care (standard medication group). Mucositis were evaluated using JCOG grade and EORTC/RTOG score by radiotherapists or dento-maxillofacial radiologists at 10 Gy intervals. Oral hygiene plans comprised motivation to maintain oral hygiene and establishing the habits of oral self care 4 times per day. Once a week, oral hygiene and oral cleaning of patients were checked by dento-maxillofacial radiologists. Oral self care included mechanical tooth brushing and a chemical mouthwash. No patients with grade 3 and score 4 mucositis were noted in the oral hygiene group. Severe mucositis occurred less frequently in the oral hygiene group than in the standard medication group. Interruption of radiotherapy due to severe mucositis did not occur in the oral hygiene group. On the other hand, interruption of radiotherapy occurred in four patients in the standard medication group, and in three it was due to severe oral pain. Our results suggested that our method of oral hygiene was more effective for alleviating acute radiation mucositis than other methods so far reported. In addition, our method is considered to be useful in preventing rampant dental caries and severe periodontitis due to the xerostomia induced by radiotherapy. (author)

  11. Oral hygiene care of patients with oral cancer during postoperative irradiation. An alleviating effect on acute radiation mucositis

    International Nuclear Information System (INIS)

    Katsura, Kouji; Masuko, Noriko; Hayashi, Takafumi; Sugita, Tadashi; Sakai, Kunio; Tsuchida, Emiko; Matsumoto, Yasuo; Sasamoto, Ryuta

    2000-01-01

    To evaluate the effect of oral hygiene care of patients with oral cancer on alleviating acute radiation mucositis. Eighteen patients receiving postoperative radiotherapy for tongue and oral floor cancer were evaluated. Radiotherapy was given in 2 Gy per fraction, 5 times a week for a total dose of 50 Gy in most patients. Radiation field included the tongue and oral floor. During radiotherapy, 8 patients were treated by dento-maxillofacial radiologists with special concern on oral hygiene (oral hygiene group) and the remaining 10 patients were treated with routine dental care (standard medication group). Mucositis were evaluated using JCOG grade and EORTC/RTOG score by radiotherapists or dento-maxillofacial radiologists at 10 Gy intervals. Oral hygiene plans comprised motivation to maintain oral hygiene and establishing the habits of oral self care 4 times per day. Once a week, oral hygiene and oral cleaning of patients were checked by dento-maxillofacial radiologists. Oral self care included mechanical tooth brushing and a chemical mouthwash. No patients with grade 3 and score 4 mucositis were noted in the oral hygiene group. Severe mucositis occurred less frequently in the oral hygiene group than in the standard medication group. Interruption of radiotherapy due to severe mucositis did not occur in the oral hygiene group. On the other hand, interruption of radiotherapy occurred in four patients in the standard medication group, and in three it was due to severe oral pain. Our results suggested that our method of oral hygiene was more effective for alleviating acute radiation mucositis than other methods so far reported. In addition, our method is considered to be useful in preventing rampant dental caries and severe periodontitis due to the xerostomia induced by radiotherapy. (author)

  12. Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Ehsan Zayerzadeh

    2016-07-01

    Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

  13. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-01-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity

  14. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Directory of Open Access Journals (Sweden)

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  15. INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

    Science.gov (United States)

    This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

  16. Acute Toxicity Evaluation of Nitroaromatic Compounds

    Science.gov (United States)

    1991-03-01

    eye of any animal during the observation period. Extreme fluorescein staining was evident in all of the test animals. Pannus (corneal vasculation) was...treated eyes at this time point showed signs of pannus . 39 0 TABLE 13 ACUTE ORAL - RANGE FINDING - RATS 1,3,5-TRINITROBENZENE Dose Dose Wt (g) Wt (g) Wt...the cornea at the 24h, 48h, 72h and 96h observation points. Additional Observations: Pannus (corneal vascularization) was noted at the 96h observation

  17. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    International Nuclear Information System (INIS)

    Dorn, Paige L.; Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J.

    2012-01-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a “field-in-field” technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m 2 . Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume 25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV volume >2,500 mL.

  18. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States); Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J. [Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States)

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

  19. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    Science.gov (United States)

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

  20. A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus and snowdrop lectin shows oral toxicity to target insects

    Directory of Open Access Journals (Sweden)

    Fitches Elaine

    2006-03-01

    Full Text Available Abstract Background Despite evidence suggesting a role in plant defence, the use of plant lectins in crop protection has been hindered by their low and species-specific insecticidal activity. Snowdrop lectin (Galanthus nivalis agglutinin; GNA is transported to the haemolymph of insects after oral ingestion, and can be used as a basis for novel insecticides. Recombinant proteins containing GNA expressed as a fusion with a peptide or protein, normally only toxic when injected into the insect haemolymph, have the potential to show oral toxicity as a result of GNA-mediated uptake. Results A gene encoding a toxin, ButaIT, from the red scorpion (Mesobuthus tamulus was synthesised and assembled into expression constructs. One construct contained ButaIT alone, whereas the other contained ButaIT fused N-terminally to a GNA polypeptide (ButaIT/GNA. Both recombinant proteins were produced using the yeast Pichia pastoris as an expression host, and purified. Recombinant ButaIT and ButaIT/GNA were acutely toxic when injected into larvae of tomato moth (Lacanobia oleracea, causing slow paralysis, leading to mortality or decreased growth. ButaIT/GNA was chronically toxic when fed to L. oleracea larvae, causing decreased survival and weight gain under conditions where GNA alone was effectively non-toxic. Intact ButaIT/GNA was detected in larval haemolymph from insects fed the fusion protein orally, demonstrating transport of the linked polypeptide across the gut. Proteolysis of the fusion protein was also observed. ButaIT/GNA was significantly more toxic that GNA alone when fed to the homopteran Nilaparvata lugens (rice brown planthopper in liquid artificial diet. Conclusion The ButaIT/GNA recombinant fusion protein is toxic to lepidopteran larvae both when injected and when fed orally, showing the utility of GNA as a carrier to transport potentially toxic peptides and proteins across the insect gut. Although ButaIT has been claimed to be lepidopteran

  1. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    International Nuclear Information System (INIS)

    Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V.

    2012-01-01

    The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ( 99m Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99m Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

  2. The acute toxicity of clove oil to fish Danio rerio and Poecilia reticulata

    Directory of Open Access Journals (Sweden)

    Petra Doleželová

    2011-01-01

    Full Text Available Clove oil (active substance eugenol is an anaesthetic used in aquaculture for stress prevention and prevention of mechanical damage during veterinary procedures. The aim of this study was to determine the acute toxicity of clove oil in two aquarium fish species - zebrafish (Danio rerio and guppy (Poecilia reticulata, which are considered the most commonly used model organisms in toxicity testing. The semi-static method according to OECD no. 203 (Fish, Acute toxicity test was used for testing the toxicity of clove oil for juvenile fish. A series of 5 acute toxicity tests was performed, with 10 fish of both species used for each concentration and for the control. The results obtained (number of dead individuals at particular test concentrations were subjected to a probit analysis using the EKO-TOX 5.2 program in order to determine 96hLC50 clove oil values. The significance of the difference between 96hLC50 values in D. rerio and P. reticulata was tested using the Mann-Whitney non-parametric test. The 96hLC50 mean value for clove oil was 18.2 ± 5.52 mg·l–1 in juvenile D. rerio and 21.7 ± 0.8 mg·l–1 in P. reticulata. In spite of variability in clove oil composition, acute toxicity values of clove oil for juvenile stages of both fish species were comparable. The results did not show different sensitivities to clove oil in tested fish species. This is the first similar study in these fish species.

  3. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    OpenAIRE

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

  4. Acute radiotherapy toxicity in 57 dogs with gross and microscopic mast cell tumours.

    Science.gov (United States)

    Blackwood, L; Tanis, J B; Harper, A; Amores-Fuster, I; Killick, D R; Finotello, R

    2018-05-15

    Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty-seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events. © 2018 John Wiley & Sons Ltd.

  5. Acute toxicity of chlorantraniliprole to non-target crayfish (Procambarus clarkii) associated with rice-crayfish cropping systems.

    Science.gov (United States)

    Barbee, Gary C; McClain, W Ray; Lanka, Srinivas K; Stout, Michael J

    2010-09-01

    Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice-crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non-target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. The aquatic 96 h median lethal toxicity (LC(50)) data indicate that technical-grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC(50) of 951 microg L(-1) (95% CL = 741-1118 microg L(-1)). A no observed effect concentration (NOEC) of 480 microg L(-1) was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole-treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda-cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice-crayfish crop rotations than pyrethroids. (c) 2010 Society of Chemical Industry.

  6. Acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus: a retrospective case-control study

    Directory of Open Access Journals (Sweden)

    Patel Ajaykumar B

    2012-02-01

    Full Text Available Abstract Background The purpose of this study was to evaluate acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus (DLE. Methods A retrospective review was performed of patients with DLE who received radiotherapy at our institution between 1980 and 2005. Patients with other connective tissue disorders were excluded. Control patients were matched 2:1 with the DLE treatment courses based on age, cancer diagnosis, year of treatment, radiotherapy dose, and sex. Acute (within 30 days from the completion of radiotherapy and late toxicities were evaluated for each treatment course using the Common Terminology Criteria for Adverse Events Version 3.0. Results Twelve patients with DLE received a total of 15 radiotherapy courses. The median follow-up time was 2.6 years (range, 0.0-15.2 years. Acute toxicity of any organ was observed in 10 (67% treatment courses, of which 2 (13% were Grade 3 or higher. Acute Grade 1 or 2 dermatologic toxicity was observed in 8 courses (53%. Late toxicity of any organ was observed in 7 of 12 (58% evaluable treatment courses, of which 3 (23% were grade 3 or higher. Late grade 1 or 2 dermatologic toxicity was observed in 5 (42% courses. No patient experienced acute or late Grade 3 or higher dermatologic toxicity. The rates of any organ or dermatologic acute and late toxicity were not significantly different between DLE and control treatment courses. Conclusions Our findings do not suggest an increased risk of toxicity to the skin or other organs in patients with DLE receiving radiotherapy.

  7. Acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus: a retrospective case-control study

    International Nuclear Information System (INIS)

    Patel, Ajaykumar B; Hallemeier, Christopher L; Petersen, Ivy A; Jensen, Ashley W; Osborn, Thomas G; Miller, Robert C

    2012-01-01

    The purpose of this study was to evaluate acute and late toxicities of radiotherapy for patients with discoid lupus erythematosus (DLE). A retrospective review was performed of patients with DLE who received radiotherapy at our institution between 1980 and 2005. Patients with other connective tissue disorders were excluded. Control patients were matched 2:1 with the DLE treatment courses based on age, cancer diagnosis, year of treatment, radiotherapy dose, and sex. Acute (within 30 days from the completion of radiotherapy) and late toxicities were evaluated for each treatment course using the Common Terminology Criteria for Adverse Events Version 3.0. Twelve patients with DLE received a total of 15 radiotherapy courses. The median follow-up time was 2.6 years (range, 0.0-15.2 years). Acute toxicity of any organ was observed in 10 (67%) treatment courses, of which 2 (13%) were Grade 3 or higher. Acute Grade 1 or 2 dermatologic toxicity was observed in 8 courses (53%). Late toxicity of any organ was observed in 7 of 12 (58%) evaluable treatment courses, of which 3 (23%) were grade 3 or higher. Late grade 1 or 2 dermatologic toxicity was observed in 5 (42%) courses. No patient experienced acute or late Grade 3 or higher dermatologic toxicity. The rates of any organ or dermatologic acute and late toxicity were not significantly different between DLE and control treatment courses. Our findings do not suggest an increased risk of toxicity to the skin or other organs in patients with DLE receiving radiotherapy

  8. [Acute onset pulmonary toxicity associated to amiodarone].

    Science.gov (United States)

    Ferreira, Pedro Gonçalo; Saraiva, Fátima; Carreira, Cláudia

    2012-01-01

    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome.

  9. Pengujian Toksisitas Akut Oral Dan Dermal pada Biolarvasida Metarhizium anisopliae terhadap Tikus Putih Spraque Dawley

    Directory of Open Access Journals (Sweden)

    Deni Zulfiana

    2016-03-01

    Full Text Available Acute oral and dermal toxicity test against white rats was conducted to determine the toxicity and side effects of bio-larvacide (Metarhizium anisopliae crude extract on humans. In the oral test used a maximum dose 5000 mg/kg and dermal testing used a maximum dose of 2000 mg/kg. Dose treatment and control tested to 5 Spraque Dawley male rats. The results showed that oral treatment with a dose of 5000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. In the dermal treatment with a dose of 2000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. Based on these results LD50 acute oral M. anisopliae biolarvacide above 5000 mg/kg and the acute dermal is above 2000 mg/kg. It was therefore concluded that the formulation of Metarhizium anisopliae biolarvasida classified as not hazardous when used in accordance with the recommendation of the class I (WHO, 2003.

  10. Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia

    DEFF Research Database (Denmark)

    Løhmann, Ditte J A; Abrahamsson, Jonas; Ha, Shau-Yin

    2016-01-01

    Treatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first...

  11. The Acute Toxicity of Major Ion Salts to Ceriodaphnia dubia. III. Mathematical models for mixture toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset concerns the development of models for describing the acute toxicity of major ions to Ceriodaphnia dubia using data from single salt tests and binary...

  12. Oral acute toxicity study of selected botanical pesticide plants used ...

    African Journals Online (AJOL)

    African Journal of Environmental Science and Technology ... The extracts were administered orally and the animals were observed for 24 h. ... Chronic studies should be carried out to assess whether these extracts have serious effects on experimental animals exposed to them at small doses for a long period of time.

  13. Evaluation of acute toxicity of genabilic acid (menbutone 10% in rabbits

    Directory of Open Access Journals (Sweden)

    S. O. El Okle

    2014-09-01

    Full Text Available Normal 0 false false false MicrosoftInternetExplorer4 A complete investigation of the acute toxicity of a choleretic compound, menbutone, was performed in rabbits, including lethal dose for 50% of rabbits determination, clinical signs observation and in vivo and post-mortem examinations. Haematological, biochemical and histopathological changes resulting from intramuscular injection of menbutone were also investigated at dose 400 mg/kg body weight. Acute toxicity of menbutone at dose of 400 mg/kg BW induced interstitial myocarditis and multifocal necrosis, whereas serum creatine phosphokinase, creatinine phosphokinase-MB isoenzyme and aspartate aminotransferase activities were significantly increased. Elevation of serum alanine aminotransferase and alkaline phosphatase activities and total bilirubin level associated with lowered albumin content was consistent with histopathological changes of hepatic tissues; hepatic necrosis and fatty infiltration were pronounced indicators of injuries. Renal tubular necrosis and interstitial nephritis were also observed in intoxicated rabbits. Menbutone also induced variations in some haematological parameters. We concluded that acute toxicity of menbutone in rabbits occurred at accidental high doses, as the lethal dose was about 50 fold over the recommended therapeutic dose for other animals. Cardiac muscle, liver and kidneys are the main target organs for menbutone toxicity. Menbutone is not recommended for use in rabbits suffering from any cardiacand hepatic disorders, especially in overdosing situations.

  14. Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

    Science.gov (United States)

    Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

    2011-09-01

    Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid.

    Science.gov (United States)

    Al-Salem, Huda S; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf

    2016-04-23

    It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.

  16. Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san.

    Science.gov (United States)

    Park, Hwayong; Hwang, Youn-Hwan; Ma, Jin Yeul

    2017-06-01

    The traditional medicine oyaksungi-san (OY) has been prescribed in East Asia for hundreds of years for the treatment of stroke, paralysis, and ataxia. OY also has therapeutic effects on arthralgia, myalgia, and rheumatoid arthritis, and recent studies have shown its protective effects against apoptosis of hippocampal cells and its anti-inflammatory effects on the peripheral blood cells of patient with cerebral infarction. Many studies have explored the use of traditional medicine and herb materials in the development of safe, novel, and effective pharmaceuticals with fewer side effects. These efforts commonly adopt a bioconversion tool for fermentation with beneficial microbes. However, only pharmaceuticals with high levels of safety and low levels of toxicity can be used in healthcare system. OY water extract was fermented with Lactobacillus and assayed for acute toxicity and genotoxicity. Single dose acute toxicity, bacterial reverse mutation, chromosome aberrations, and micronucleus were observed and assayed in rats, histidine/tryptophan auxotrophic bacteria, Chinese hamster ovary fibroblast cells, and mice bone marrow cells, respectively. All the experimental animals showed no abnormal behavior, clinical signs, body weight increases, or mortality. In the bacterial cultures, no revertant colonies were observed. Morphological and numerical chromosomal aberrations were not found in all metaphases examined. Frequency of induced micronuclei was not significantly increased in all doses applied. As a whole, no acute toxicity or genotoxicity were observed in all the assays examined. Therefore, fermented OY is considered to be a safe material that can be used for development of complementary and alternative medicine using bioconversion.

  17. Methotrexate-induced acute toxic leukoencephalopathy

    Directory of Open Access Journals (Sweden)

    Parag R Salkade

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX, as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS. Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced ′acute toxic leukoencephalopathy′ has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted and FLAIR (Fluid-Attenuated Inversion recovery sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up

  18. Derivation of an oral toxicity reference value for nickel.

    Science.gov (United States)

    Haber, Lynne T; Bates, Hudson K; Allen, Bruce C; Vincent, Melissa J; Oller, Adriana R

    2017-06-15

    Nickel (Ni) is in the earth's crust and can be found in environmental compartments such as water, soil, and air, as well as food. This paper presents an assessment of the oral nickel toxicity data in support of non-cancer health-based oral exposure limits or toxicity reference values (TRVs). This paper derives TRVs for three populations of interest: adults, toddlers, and people who have been dermally sensitized to nickel. The adult/lifetime TRV of 20 μg Ni/kg-day is based on post-implantation loss/perinatal mortality in a 2-generation reproductive study in rats. Several recent assessments by regulatory agencies have used the same study and endpoint, but the dose-response modeling conducted here was more appropriate for the study design. Toxicokinetic data from rats and humans indicate that the applied uncertainty factors are very conservative. Because the endpoint relates to fetal exposure and is not relevant to toddlers, a toddler TRV was derived based on decreased body weight in young rats; this TRV was also 20 μg Ni/kg-day. A separate TRV of 4 μg Ni/kg in addition to Ni in food was derived for protection of nickel-sensitized populations from flare-up of dermatitis, based on studies of single exposures in humans under conditions that maximize oral absorption. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Asparaginase-Associated toxicity in children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

    N. Hijiya (Nobuko); I.M. van der Sluis (Inge)

    2016-01-01

    textabstractAsparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with

  20. Oral hygiene and mouth care for older people in acute hospitals: part 2.

    Science.gov (United States)

    Steel, Ben J

    2017-11-30

    Acute hospital admission provides an excellent opportunity to address poor oral health in older people, a group rarely seen by dental professionals and for who oral health activity in hospital is inconsistent and generally suboptimal. This two-part article explores oral hygiene and mouth care provision for older adults in acute hospitals. The first article presented the findings of a literature review exploring oral and dental disease in older adults, the importance of good oral health and mouth care, and the current situation. The second article explores clinical recommendations. A change in philosophy is needed to embed oral care as an essential component of holistic practice. More research is needed to determine the best ways to assess and treat oro-dental problems in older people, and promote and restore their oral health in hospitals. Great potential exists to innovate and develop new ways of providing care to this group. ©2017 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  1. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  2. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V. [Division of Pharmaceutical Technology, Defence Research Laboratory, Assam (India); Department of Life Sciences, Defense Research Development and Organization, New Delhi (India)

    2012-07-01

    The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ({sup 99m} Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of {sup 99m}Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

  3. Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

    Directory of Open Access Journals (Sweden)

    P Chattopadhyay

    2012-01-01

    Full Text Available The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.

  4. Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.

    Science.gov (United States)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    International Nuclear Information System (INIS)

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-01-01

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity

  6. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); EMR3738, Université Lyon 1, Lyon (France); Decullier, Evelyne; Bin, Sylvie [Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon (France); Université Lyon 1, Lyon (France); EA SIS, Université de Lyon, Lyon (France); Faix, Antoine [Department of Urology, Clinique Beausoleil, Montpellier (France); Ruffion, Alain [Université Lyon 1, Lyon (France); Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Jalade, Patrice [Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Fenoglietto, Pascal [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France); Udrescu, Corina; Enachescu, Ciprian [Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite (France); Azria, David [Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier (France)

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  7. Phytochemical screening, cytotoxicity and acute toxicity of Annona ...

    African Journals Online (AJOL)

    Phytochemical screening, cytotoxicity and acute toxicity of Annona vepretorum Mart (Annonaceae) leaf extracts. Mariana G e Silva, Ana P de Oliveira, Camila de S Araújo, Érica M de Lavor, Juliane C Silva, Rosemairy L Mendes, Cláudia do Ó Pessoa, Marcília P Costa, Jackson R G da S Almeida ...

  8. The Study on Acute Subacute Toxicity and Anti-cancer Effect of K-herbal-acupuncture

    Directory of Open Access Journals (Sweden)

    Kwang-Ho, Kim

    2003-02-01

    Full Text Available Objectives : The purpose of this study was to investigate Acute· Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K- herbal-acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. LD50 of K-Herbal-acupuncture was limited 4×10-3ml/kg~2×10-3ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(p<0.05 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (p<0.05 6. In subacute toxicity test of complete blood count test (CBC of rat, HCT was decreased in treatments, compared with the normal group.(p<0.05 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (p<0.05 8. Median survival time was increased about 45% in treatment groups compared with the control group.(p<0.05 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(p<0.005 11. In making an examination of metastatic cancer with the naked eye, melanoma

  9. Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

    Science.gov (United States)

    Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

    2015-01-01

    The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

  10. Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

    International Nuclear Information System (INIS)

    Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

    2001-01-01

    Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

  11. Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

    Science.gov (United States)

    de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

    2017-07-01

    Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (ptest, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

    Science.gov (United States)

    Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

    2012-04-01

    The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Acute and subacute toxicity of 10B-paraboronophenylalanine

    International Nuclear Information System (INIS)

    Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C.

    1989-01-01

    The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug

  14. Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

    Science.gov (United States)

    Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

    2013-08-01

    To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

  15. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    Science.gov (United States)

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with a cryptococcal infection and was reduced or absent in the early and late stages of disease. The clinical course and histopathology were consistent with those for shock. There was considerable variation between mouse strains in susceptibility to toxicity. Swiss Webster mice from the Charles River colony were most susceptible, followed by C3H/He, BALB/c, and C57BL/6 mice. DBA/2 mice and Swiss Webster mice from the Simonsen colony were resistant. Acute toxicity was mimicked by injection of preformed complexes of MAb and purified polysaccharide. The toxic effect was also produced by injection of MAbs into mice that were preloaded with polysaccharide. The toxic effect was not blocked by treatment of mice with chloropheniramine or anti-tumor necrosis factor alpha antibodies or by depletion of complement components via pretreatment with cobra venom factor. Toxicity was reduced by treatment of mice with high doses of epinephrine, dexamethasone, or chlorpromazine. Finally, the toxic effect was completely blocked by treatment of mice with the platelet-activating factor antagonist WEB 2170 BS or by pretreatment of mice with the liposome-encapsulated drug dichloromethylene diphosphonate, a procedure which depletes macrophages from the spleen and liver. PMID:9125564

  16. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  17. Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

    Science.gov (United States)

    Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

    2018-01-02

    Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

  18. Moist skin care can diminish acute radiation-induced skin toxicity

    International Nuclear Information System (INIS)

    Momm, F.; Weissenberger, C.; Bertelt, S.; Henke, M.

    2003-01-01

    Background: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. Patients and Methods: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. Results: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). Conclusion: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors. (orig.)

  19. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  20. Polyaluminium chloride (PAX-18) - acute toxicity and toxicity for early development stages of common carp (Cyprinus carpio)

    Czech Academy of Sciences Publication Activity Database

    Mácová, S.; Máchová, J.; Prokeš, Miroslav; Plhalová, L.; Široká, Z.; Dlesková, K.; Doleželová, P.; Svobodová, Z.

    2009-01-01

    Roč. 30, Suppl. 1 (2009), s. 192-198 ISSN 0172-780X. [Interdisciplinary Czech-Slovak Toxicological Conference /14./. Brno, 01.06.2009-03.06.2009] R&D Projects: GA MZe QH71305 Institutional research plan: CEZ:AV0Z60930519 Keywords : fish * acute toxicity test * embryo-larval toxicity test * pH Subject RIV: GL - Fishing Impact factor: 1.047, year: 2009 http://node.nel.edu/?node_id=9497

  1. Oral toxicity of Miglyol 812(®) in the Göttingen(®) minipig.

    Science.gov (United States)

    Le Bars, G; Dion, S; Gauthier, B; Mhedhbi, S; Pohlmeyer-Esch, G; Comby, P; Vivan, N; Ruty, B

    2015-12-01

    Miglyol 812(®), a mixture of medium-chain triglycerides, has been identified as an oral vehicle that could improve the solubility and possibly the bioavailability of orally administered drugs during the non-clinical safety assessment. The toxicity of Miglyol was assessed in Göttingen(®) minipigs upon daily oral administration (gavage) for six weeks, at dosing-volumes of 0.5 and 2 mL/kg/day, compared to controls receiving 0.5% CarboxyMethylCellulose/0.1% Tween(®) 80 in water at 2 mL/kg/day. The control vehicle did not induce any findings. Miglyol at 0.5 and 2 mL/kg/day induced transient tremors, abnormal color of feces and increase in triglycerides. Miglyol at 2 ml/kg/day also induced reduced motor activity, decreased food intake, respiratory signs (2/6 animals) and increased total and LDL-cholesterol. At necropsy, the lung of 3/6 animals treated at 2 mL/kg/day presented abnormal color and/or irregular surface correlated with a chronic bronchiolo-alveolar inflammation. This finding is probably due to aspiration pneumonia in relation to the administration method and the high viscosity of Miglyol. Overall, the oral administration of pure Miglyol 812(®) for six weeks up to 2 mL/kg was less tolerated than that of the control vehicle. Miglyol as vehicle for sub-chronic oral toxicity studies in minipigs should be used with a limited dosing-volume. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

    Science.gov (United States)

    Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

    2015-08-01

    Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. © 2015 SETAC.

  3. Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

    Science.gov (United States)

    Sireeratawong, Seewaboon; Itharat, Arunporn; Khonsung, Parirat; Lertprasertsuke, Nirush; Jaijoy, Kanjana

    2013-01-01

    Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

  4. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

    Directory of Open Access Journals (Sweden)

    Saad Musbah Alasil

    2014-01-01

    Full Text Available The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237, phospholipase A2 inhibitor C21H36O5 (MW 368.512, and an antibacterial agent C14H11N3O2 (MW 253.260. The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups P>0.05. Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections.

  5. Acute toxicity of potassium permanganate to fingerlings of the ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-18

    Jul 18, 2008 ... Key words: Potassium permanganate, acute toxicity, LC50, LT50, behaviour, Clarias gariepinus, Nigeria. ... soft waters where other chemicals, such as copper sulphate, were too .... The temperature (oC) was measured by dipping a dry bulb thermo- .... (KMnO4) interferes with the respiratory mechanisms of.

  6. Evaluation of acute and subacute toxicities of aqueous ethanolic ...

    African Journals Online (AJOL)

    Evaluation of acute and subacute toxicities of aqueous ethanolic extract of leaves of Senna alata (L.) Roxb (Ceasalpiniaceae) ... Significant variation (P<0.05) of the body weight was observed after 26 days of treatment, in some biochemicals index of serum and 20% liver homogenates (glutathione , alkaline phosphatase ...

  7. Acute toxicity and sleep-wake EEG analysis of Stachtarpheta ...

    African Journals Online (AJOL)

    The effect of systemic administration of TASC on sleep architecture in rats was also evaluated in Sprague-Dawley rats that were chronically implanted with electrodes for electroencephalogram (EEG) and electromyogram (EMG) recording. The acute toxicity test revealed no lethal effect with doses of SCCR (up to 2000 ...

  8. Acute toxicity study of methanolic extract of Asparagus pubescens ...

    African Journals Online (AJOL)

    The acute toxicity study of methanolic extract of Asparagus pubescens root was studied on rats. The indices of the study were the liver enzymes (transaminases), cholesterol, creatinine and urea serum levels as well as the ionic analysis. Both alanine aminotransferase (ALT) and. Aspartate aminotransferase (AST) showed a ...

  9. Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

    Science.gov (United States)

    Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

    2015-11-01

    The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...

  11. Renal toxicity caused by oral use of medicinal plants: the yacon example.

    Science.gov (United States)

    de Oliveira, Rejane Barbosa; de Paula, Daniela Aparecida Chagas; Rocha, Bruno Alves; Franco, João José; Gobbo-Neto, Leonardo; Uyemura, Sérgio Akira; dos Santos, Wagner Ferreira; Da Costa, Fernando Batista

    2011-01-27

    Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs). The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys. The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic

  12. Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san

    Directory of Open Access Journals (Sweden)

    Hwayong Park

    2017-06-01

    Conclusion: As a whole, no acute toxicity or genotoxicity were observed in all the assays examined. Therefore, fermented OY is considered to be a safe material that can be used for development of complementary and alternative medicine using bioconversion.

  13. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

  14. Acute toxicity testing of some herbicides-, alkaloids-, and antibiotics-metabolizing soil bacteria in the rat.

    Science.gov (United States)

    Kaiser, A; Classen, H G; Eberspächer, J; Lingens, F

    1981-01-01

    Seven strains of soil bacteria with the ability to metabolize herbicides, alkaloids or antibiotics were tested in rats for acute toxicity. 1. Upon oral administration of 9.0 x 10(8) to 6.6 x 10(10) cells daily during 7 d no adverse reactions were observed. 2. Exposure by air did not lead to specific pulmonary changes. 3. Intracutaneous injection of 7.5 x 10(6) to 1.4 x 10(8) cells did not lead to adverse skin reactions. 4. Intraperitoneal injections up to 10(8) cells per animal did not kill rats although bacteria entered blood. At higher concentrations some mortality occurred partly due to unspecific stress reactions. 5. Animal data and observations on 20 humans being exposed to these strains for 2 months up to 15 years support the view that the bacteria tested are essentially harmless for health.

  15. Acute Inhalation Toxicity and Blood Absorption of 2,4-Dinitroanisole (DNAN) in Rats

    Science.gov (United States)

    2015-03-17

    light/dark cycle. A certified pesticide -free rodent chow (Harlan Teklad ® , 8728C Certified Rodent Diet) and drinking quality water were available ad...respiration, toxicity, blood, concentration, alternative, welfare, method, model, in vitro, pain, distress, simulate, video , computer, replacement, refinement...Prevention, Pesticides , and Toxic Substances. December 2002. Health Effects Test Guidelines: OPPTS 870.1000, Acute Toxicity Testing - Background. EPA

  16. The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

  17. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    Directory of Open Access Journals (Sweden)

    M.Y. Matti

    2015-06-01

    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  18. Treatment of Acute Tacrolimus Toxicity with Phenytoin in Solid Organ Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Arin S. Jantz

    2013-01-01

    Full Text Available The pharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations. The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400 mg/day of phenytoin for two to three days. Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects. Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity.

  19. Acute oral toxicity test and phytochemistry of some west african ...

    African Journals Online (AJOL)

    (SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1,2,4 and 8, PN; 2.5, 5, 10 and 20, OC; 5,10,20 and 40, FC; 1,2,4 and 8, HE; 4,8,16,32) of the aqueous extract of each plant (g/kg body weight) after 12hours fasting. Results: The dry ...

  20. Oral cadmium chloride intoxication in mice: Effects of penicillamine, dimercaptosuccinic acid and related compounds

    International Nuclear Information System (INIS)

    Andersen, O.; Nielsen, J.B.

    1988-01-01

    The antidotal efficacies of chelators during acute cadmium intoxication has previously been examined in experiments where both a soluble cadmium salt and the chelator were administered parenterally. In the present study, PA, DMSA and related compounds were studied as oral antidotes during oral CdCl 2 intoxication. According to the antagonistic effects noted on mortality, peristaltic toxicity and intestinal cadmium uptake, the relative efficacies of the compounds tested were: DMSA>PAD>DMPS>MSA>PA>NAPA. None of the chelators induced major changes in the organ distribution of absorbed cadmium, in particular no increased cerebral deposition of cadmium. This study indicates that, in oral cadmium intoxication in humans, orally administered DMSA would be likely to offer protection against the local toxicity of cadmium in the gastrointestinal tract as well as to reduce the risk of systemic toxicity of absorbed cadmium. (author)

  1. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

    DEFF Research Database (Denmark)

    Wollenberger, Leah; Halling-Sørensen, B.; Kusk, Kresten Ole

    2000-01-01

    The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC...

  2. Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

    International Nuclear Information System (INIS)

    Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.

    1995-01-01

    The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA's Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity

  3. Subchronic oral toxicity of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Kim Yong

    2010-08-01

    Full Text Available Abstract Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm over a period of 13 weeks (90 days in F344 rats following Organization for Economic Cooperation and Development (OECD test guideline 408 and Good Laboratory Practices (GLP. Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group: vehicle control, low-dose (30 mg/kg, middle-dose (125 mg/kg, and high-dose (500 mg/kg. After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level of 30 mg/kg and LOAEL (lowest observable adverse effect level of 125 mg/kg are suggested from the present study.

  4. Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Ito, Kazuto; Saitoh, Jun-ichi; Noda, Shin-ei; Harashima, Koichi; Sakurai, Hideyuki; Nakayama, Yuko; Yamamoto, Takumi; Suzuki, Kazuhiro; Nakano, Takashi; Niibe, Hideo

    2005-01-01

    Purpose: Several investigations have revealed that the α/β ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. Methods and Materials: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the α/β ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on

  5. Acute Toxicity Comparison of Single-Walled Carbon Nanotubes in Various Freshwater Organisms

    Directory of Open Access Journals (Sweden)

    Eun Kyung Sohn

    2015-01-01

    Full Text Available While the commercialization of single-walled carbon nanotubes (SWCNTs is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris, a microcrustacean (Daphnia magna, and a fish (Oryzias latipes based on OECD test guidelines (201, 202, and 203. According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50 of 29.99 and 30.96 mg/L, respectively, representing “acute category 3” in the Globally Harmonized System (GHS of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish.

  6. Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

    Science.gov (United States)

    Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

    2017-11-01

    This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

  7. A re-evaluation of PETROTOX for predicting acute and chronic toxicity of petroleum substances.

    Science.gov (United States)

    Redman, Aaron D; Parkerton, Thomas F; Leon Paumen, Miriam; Butler, Josh D; Letinski, Daniel J; den Haan, Klass

    2017-08-01

    The PETROTOX model was developed to perform aquatic hazard assessment of petroleum substances based on substance composition. The model relies on the hydrocarbon block method, which is widely used for conducting petroleum substance risk assessments providing further justification for evaluating model performance. Previous work described this model and provided a preliminary calibration and validation using acute toxicity data for limited petroleum substance. The objective of the present study was to re-evaluate PETROTOX using expanded data covering both acute and chronic toxicity endpoints on invertebrates, algae, and fish for a wider range of petroleum substances. The results indicated that recalibration of 2 model parameters was required, namely, the algal critical target lipid body burden and the log octanol-water partition coefficient (K OW ) limit, used to account for reduced bioavailability of hydrophobic constituents. Acute predictions from the updated model were compared with observed toxicity data and found to generally be within a factor of 3 for algae and invertebrates but overestimated fish toxicity. Chronic predictions were generally within a factor of 5 of empirical data. Furthermore, PETROTOX predicted acute and chronic hazard classifications that were consistent or conservative in 93 and 84% of comparisons, respectively. The PETROTOX model is considered suitable for the purpose of characterizing petroleum substance hazard in substance classification and risk assessments. Environ Toxicol Chem 2017;36:2245-2252. © 2017 SETAC. © 2017 SETAC.

  8. Toxicity of binary chemical munition destruction products: methylphosphonic acid, methylphosphinic acid, 2-diisopropylaminoethanol, DF neutralent, and QL neutralent.

    Science.gov (United States)

    Watson, Rebecca E; Hafez, Ahmed M; Kremsky, Jonathan N; Bizzigotti, George O

    2007-01-01

    This paper reports the toxicity and environmental impact of neutralents produced from the hydrolysis of binary chemical agent precursor chemicals DF (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl methylphosphonite). Following a literature review of the neutralent mixtures and constituents, basic toxicity tests were conducted to fill data gaps, including acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF neutralent, the acute oral LD(50) in the Sprague-Dawley rat was measured at 1888 mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium and Escherichia coli was negative. The 48-h LC(50) values for pH-adjusted DF neutralent with Daphnia magna and Cyprinodon variegatus were > 2500 mg/L and 1593 mg/L, respectively. The acute oral LD(50) values in the rat for QL neutralent constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were both determined to be 940 mg/kg, and the Ames test was negative for both. Good Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D. magna EC(50) values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C. variegatus assays on MP and KB gave LC(50) values of 73 and 252 mg/L, respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD(50) values for acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD(50) values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using these data, the overall toxicity of the neutralents was assessed.

  9. Acute toxicity of Opuntia ficus indica and Pistacia lentiscus seed oils in mice.

    Science.gov (United States)

    Boukeloua, A; Belkhiri, A; Djerrou, Z; Bahri, L; Boulebda, N; Hamdi Pacha, Y

    2012-01-01

    Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD₅₀ values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opuntia ficus indica seeds were extracted and analyzed for its chemical and physical properties such as acid value, free fatty acid percentage (% FFA), iodine index, and saponification value as well as refractive index and density. LD₅₀ values obtained by single doses, orally and intraperitoneally administered in mice, were respectively 43 ± 0,8 ;[40.7- 45.4 ] ml/kg body wt. p.o. and 2.72 ± 0,1 ;[2.52-2.92] ml/kg body wt. i.p. for Opuntia ficus indica ; and 37 ± 1 ;[34.4 - 39.8 ] ml/kg body wt. p.o. and 2.52 ± 0,2 ;[2.22 - 2.81 ] ml/kg body wt. i.p. for Pistacia lentiscus respectively. The yields of seed oil were respectively calculated as 20.25% and 10.41%. The acid and free fatty acid values indicated that the oil has a low acidity.

  10. Identifying and designing chemicals with minimal acute aquatic toxicity.

    Science.gov (United States)

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

    2015-05-19

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

  11. The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

    International Nuclear Information System (INIS)

    Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

    2011-01-01

    Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm 3 , respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm 3 ) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm 3 increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

  12. Psychosis associated with acute recreational drug toxicity: a European case series.

    Science.gov (United States)

    Vallersnes, Odd Martin; Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Dargan, Paul I

    2016-08-18

    Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset. Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations. The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and

  13. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

    Science.gov (United States)

    Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

    2017-11-01

    Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

  14. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    International Nuclear Information System (INIS)

    Jensen, Alexandra D; Nikoghosyan, Anna V; Ecker, Swantje; Ellerbrock, Malte; Debus, Jürgen; Münter, Marc W

    2011-01-01

    To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted

  15. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Directory of Open Access Journals (Sweden)

    Basak Ozlem Perk

    2013-01-01

    Full Text Available The fruit of Physalis peruviana L. (PPL has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  16. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    Science.gov (United States)

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender.

  17. Two cases of acute generalized exanthematous pustulosis related to oral terbinafine and an analysis of the clinical reaction pattern.

    Science.gov (United States)

    Eyler, Jennifer T; Squires, Stephen; Fraga, Garth R; Liu, Deede; Kestenbaum, Thelda

    2012-11-15

    Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern characterized by the rapid appearance of widespread sterile, nonfollicular pustules arising within edematous erythematous skin. This aseptic pustular eruption is commonly accompanied by leukocytosis and fever and usually follows recent administration of oral or parenteral drugs. We report two cases of terbinafine-induced AGEP in male patients. Both patients developed a generalized erythroderma with scaling and pruritic pustules 7 and 14 days following initiation of oral terbinafine. With immediate discontinuation of terbinafine and various treatment protocols, both patients demonstrated recovery followed by skin desquamation during the subsequent weeks. Terbinafine is the most frequently used systemic antimycotic and antifungal medication, reflecting its superior efficacy for dermatophyte infections. Despite the appealing drug profile, an awareness of terbinafine-induced AGEP is important given the 5 percent mortality associated with AGEP. Additionally, distinguishing the characteristics of AGEP from those associated with toxic epidermal necrolysis, Stevens-Johnson syndrome, and generalized pustular psoriasis allows for prompt dermatologic evaluation, accurate diagnosis, and appropriate treatment.

  18. 40 CFR 156.62 - Toxicity Category.

    Science.gov (United States)

    2010-07-01

    .... Acute Toxicity Categories for Pesticide Products Hazard Indicators I II III IV Oral LD50 Up to and including 50 mg/kg >50 thru 500 mg/kg >500 thru 5,000 mg/kg >5,000 mg/kg Dermal LD50 Up to and including 200 mg/kg >200 thru 2000 mg/kg >2000 thru 20,000 mg/kg >20,000 mg/kg Inhalation LC50 Up to and including...

  19. Acute toxicity of uranium hexafluoride, uranyl fluoride and hydrogen fluoride

    International Nuclear Information System (INIS)

    Just, R.A.

    1988-01-01

    Uranium hexafluoride (UF 6 ) released into the atmosphere will react rapidly with moisture in the air to form the hydrolysis products uranyl fluoride (UO 2 F 2 ) and hydrogen fluoride (HF). Uranium compounds such as UF 6 and UO 2 F 2 exhibit both chemical toxicity and radiological effects, while HF exhibits only chemical toxicity. This paper describes the development of a methodology for assessing the human health consequences of a known acute exposure to a mixture of UF 6 , UO 2 F 2 , and HF. 4 refs., 2 figs., 5 tabs

  20. Irradiation in the setting of collagen vascular disease: acute and late toxicity

    International Nuclear Information System (INIS)

    Morris, Monica; Powell, Simon

    1996-01-01

    Purpose: Based upon reports of greater toxicity from radiation therapy, collagen vascular diseases have been considered a contraindication to irradiation. We assessed the acute and late complication rate of radiation therapy in patients with collagen vascular disease. Methods and Materials: A retrospective chart review was undertaken to analyze acute and late toxicity in the 96 patients with documented collagen vascular disease (CVD) who were irradiated between 1960 and 1995. The majority had rheumatoid arthritis (55); 14 had systemic lupus erythematosus; 7 polymyositis or dermatomyositis; 7 ankylosing spondylitis; 4 scleroderma; 2 juvenile rheumatoid arthritis; and the remainder various mixed connective tissue disorders. Mean follow up of survivors was 6.3 years from time of irradiation. Treatment was megavoltage in all but 8 cases. Doses ranged from 6 to 70Gy, with an average of 41.7Gy. Treatment of 32 sites was combined with chemotherapy, 15 concurrent with irradiation. Surgery was involved in the treatment of 46 sites. Toxicity was scored using the RTOG acute and the RTOG/EORTC Late Effects on Normal Tissues radiation morbidity scoring scales. Results: Overall, 127 sites were evaluable in 96 patients. Significant (grade 3 or higher) acute complications were seen in 15 of 127 (11.8%) of irradiated sites. The actuarial incidence of significant late complications at 5 and 10 years was 16% and 24%, respectively. There was a single in-field sarcoma. 2 patients had treatment-related deaths, one from leukencephalopathy and the other from postoperative wound infection. Univariate analysis revealed late effects to be more severe in those receiving combined modality treatment (p=.03), and in those with significant acute reactions (p=.0001). Patients with rheumatoid arthritis had less severe late effects than those with other collagen vascular diseases (6% vs 37% at 5 years, p=.0001). We did not demonstrate a difference in late effects according to radiation dose, timing

  1. Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata

    NARCIS (Netherlands)

    Sumon, Kizar Ahmed; Saha, Sampa; Brink, van den Paul J.; Peeters, Edwin T.H.M.; Bosma, Roel H.; Rashid, Harunur

    2017-01-01

    This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10

  2. Subchronic (13-week) oral toxicity study of α-cyclodextrin in dogs

    NARCIS (Netherlands)

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The oral toxicity of α-cyclodextrin (α-CD) was examined in a 13-week feeding study in which groups of Beagle dogs received α-CD in the diet at concentrations of 0 (control), 5, 10, or 20% (4dogs/sex/group). No treatment-related changes were noted in behavior or appearance of the dogs and no

  3. Subchronic (13-week) oral toxicity study of y-cyclodextrin in dogs

    NARCIS (Netherlands)

    Til, H.P.; Bär, A.

    1998-01-01

    The oral toxicity of γ-cyclodextrin (γ- CD) was examined in a 13-week feeding study in which four groups of four male and four female Beagle dogs received γ-CD in the diet at concentrations of 0 (control), 5, 10, or 20%. No treatment-related changes were noted in behavior or appearance of the dogs

  4. Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC).

    LENUS (Irish Health Repository)

    Walsh, Lorraine

    2011-01-01

    We retrospectively reviewed acute toxicity with cetuximab and radiotherapy, comparing it with a matched cisplatin group. The cetuximab group experienced significantly more toxicity--grade ≥3 oral mucositis (p=0.014), skin dermatitis (p=0.0004), ≥10% weight loss (p=0.03), and enteral feeding requirement (p=0.05). This finding of enhanced toxicity is similar to recent publications.

  5. Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species

    OpenAIRE

    Addy-Orduna, Laura M.; Zaccagnini, María-Elena; Canavelli, Sonia B.; Mineau, Pierre

    2011-01-01

    It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD50) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be...

  6. Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

    Science.gov (United States)

    Kent, Marc; Creevy, Kate E; Delahunta, Alexander

    2010-01-01

    Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

  7. Acute toxicity studies of aqueous stem bark extract of Ximenia ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-16

    May 16, 2008 ... the aqueous stem bark extract revealed the presence of cardiac ... needs of rural populations in African and other third world ... Table 1. Phytochemical screening of Ximenia Americana. ... Table 2. Post mortem gross pathology result of acute toxicity of ... while the treated groups showed variable weight loss.

  8. Oral bioaccessibility of toxic metals in contaminated oysters and relationships with metal internal sequestration.

    Science.gov (United States)

    Gao, Shi; Wang, Wen-Xiong

    2014-12-01

    The Hong Kong oysters Crassostrea hongkongensis are widely farmed in the estuarine waters of Southern China, but they accumulate Cu and Zn to alarmingly high concentrations in the soft tissues. Health risks of seafood consumption are related to contaminants such as toxic metals which are bioaccessible to humans. In the present study, we investigated the oral bioaccessibility of five toxic metals (Ag, Pb, Cd, Cu and Zn) in contaminated oysters collected from different locations of a large estuary in southern China. In all oysters, total Zn concentration was the highest whereas total Pb concentration was the lowest. Among the five metals, Ag had the lowest oral bioaccessibility (38.9-60.8%), whereas Cu and Zn had the highest bioaccessibility (72.3-93.1%). Significant negative correlation was observed between metal bioaccessibility and metal concentration in the oysters for Ag, Cd, and Cu. We found that the oral bioaccessibility of the five metals was positively correlated with their trophically available metal fraction (TAM) in the oyster tissues, and negatively correlated with metal distribution in the cellular debris. Thus, metal partitioning in the TAM and cellular debris controlled the oral bioaccessibility to humans. Given the dependence of oral bioaccessibility on tissue metal contamination, bioaccessibility needs to be incorporated in the risk assessments of contaminated shellfish. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  10. Disinfection in Wastewater Treatment Plants: Evaluation of Effectiveness and Acute Toxicity Effects

    Directory of Open Access Journals (Sweden)

    Maria Cristina Collivignarelli

    2017-09-01

    Full Text Available In Italy, urban wastewater disinfection is regulated in the third part of Legislative Decree n. 152/2006, which states that wastewater treatment plants (WWTPs must include a disinfection unit, with a capacity exceeding 2000 Population Equivalent (PE. This treatment shall ensure microbial quality and health security. The legislation provides the following limits for wastewater: Escherichia coli (E. coli concentration below 5000 CFU 100 mL−1 (recommended value, active chlorine concentration below 0.2 mg L−1 and lack of acute toxicity. The compliance with these conditions is shown by means of the study of correct disinfectant dosage, which also depends on wastewater characteristics. An investigation at the regional level (from 2013 to 2016 shows a correlation between acute toxicity discharge and disinfection treatment through chemical reagents (mainly with the use of chlorine compounds and peracetic acid. The experimental work concerns two active sludge WWTPs in northern Italy with small capacity (10,000–12,000 PE. The activities provide the assessment of microbiological quality and toxicity of WWTPs effluents in relation to the dosage of sodium hypochlorite and peracetic acid, by means of the use of batch tests. The results show that with similar disinfectant dosage and comparable initial E. coli concentration, peracetic acid exhibits the best performance in terms of microbial removal (with removal yields up to 99.99%. Moreover, the acute toxicity was evident at higher doses and therefore with higher residuals of peracetic acid (2.68 mg L−1 compared to the free residual chlorine (0.17 mg L−1.

  11. Assessment of Grape, Plum and Orange Synthetic Food Flavourings Using in vivo Acute Toxicity Tests

    Directory of Open Access Journals (Sweden)

    Ila Monize Sousa Sales

    2017-01-01

    Full Text Available The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

  12. Use of fractional dose–volume histograms to model risk of acute rectal toxicity among patients treated on RTOG 94-06

    International Nuclear Information System (INIS)

    Tucker, Susan L.; Michalski, Jeff M.; Bosch, Walter R.; Mohan, Radhe; Dong, Lei; Winter, Kathryn; Purdy, James A.; Cox, James D.

    2012-01-01

    Background and purpose: For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose–volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman–Kutcher–Burman (LKB) model is based on the fractional rectal dose–volume histogram (DVH). Materials and methods: Grade ⩾2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered. Results: The majority of patients experiencing Grade ⩾2 acute rectal toxicity did so before completion of radiotherapy (70/80 = 88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n = 1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P = 0.024). Conclusions: Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered.

  13. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    Science.gov (United States)

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. Copyright © 2011 SETAC.

  14. Acute toxicity assessment of explosive-contaminated soil extracting solution by luminescent bacteria assays.

    Science.gov (United States)

    Xu, Wenjie; Jiang, Zhenming; Zhao, Quanlin; Zhang, Zhenzhong; Su, Hongping; Gao, Xuewen; Ye, Zhengfang

    2016-11-01

    Explosive-contaminated soil is harmful to people's health and the local ecosystem. The acute toxicity of its extracting solution was tested by bacterial luminescence assay using three kinds of luminescent bacteria to characterize the toxicity of the soil. An orthogonal test L 16 (4 5 ) was designed to optimize the soil extracting conditions. The optimum extracting conditions were obtained when the ultrasonic extraction time, ultrasonic extraction temperature, and the extraction repeat times were 6 h, 40 °C, and three, respectively. Fourier transform infrared spectroscopy (FTIR) results showed that the main components of the contaminated soil's extracting solution were 2,4-dinitrotoluene-3-sulfonate (2,4-DNT-3-SO 3 - ); 2,4-dinitrotoluene-5-sulfonate (2,4-DNT-5-SO 3 - ); and 2,6-dinitrotoluene (2,6-DNT). Compared with Photobacterium phosphoreum and Vibrio fischeri, Vibrio qinghaiensis sp. Nov. is more suitable for assessing the soil extracting solution's acute toxicity. Soil washing can remove most of the contaminants toxic to luminescent bacterium Vibrio qinghaiensis sp. Nov., suggesting that it may be a potential effective remediation method for explosive-contaminated soil.

  15. Oral microbiota species in acute apical endodontic abscesses

    Directory of Open Access Journals (Sweden)

    Noelle George

    2016-03-01

    Full Text Available Background and objectives: Acute apical abscesses are serious endodontic diseases resulting from pulpal infection with opportunistic oral microorganisms. The objective of this study was to identify and compare the oral microbiota in patients (N=18 exhibiting acute apical abscesses, originating from the demographic region in Portland, Oregon. The study hypothesis is that abscesses obtained from this demographic region may contain unique microorganisms not identified in specimens from other regions. Design: Endodontic abscesses were sampled from patients at the Oregon Health & Science University (OHSU School of Dentistry. DNA from abscess specimens was subjected to polymerase chain reaction amplification using 16S rRNA gene-specific primers and Cy3-dCTP labeling. Labeled DNA was then applied to microbial microarrays (280 species generated by the Human Oral Microbial Identification Microarray Laboratory (Forsyth Institute, Cambridge, MA. Results: The most prevalent microorganisms, found across multiple abscess specimens, include Fusobacterium nucleatum, Parvimonas micra, Megasphaera species clone CS025, Prevotella multisaccharivorax, Atopobium rimae, and Porphyromonas endodontalis. The most abundant microorganisms, found in highest numbers within individual abscesses, include F. nucleatum, P. micra, Streptococcus Cluster III, Solobacterium moorei, Streptococcus constellatus, and Porphyromonas endodontalis. Strong bacterial associations were identified between Prevotella multisaccharivorax, Acidaminococcaceae species clone DM071, Megasphaera species clone CS025, Actinomyces species clone EP053, and Streptococcus cristatus (all with Spearman coefficients >0.9. Conclusions: Cultivable and uncultivable bacterial species have been identified in endodontic abscesses obtained from the Portland, Oregon demographic region, and taxa identifications correlated well with other published studies, with the exception of Treponema and Streptococcus cristae, which

  16. Oral microbiota species in acute apical endodontic abscesses.

    Science.gov (United States)

    George, Noelle; Flamiatos, Erin; Kawasaki, Kellie; Kim, Namgu; Carriere, Charles; Phan, Brian; Joseph, Raphael; Strauss, Shay; Kohli, Richie; Choi, Dongseok; Baumgartner, J Craig; Sedgley, Christine; Maier, Tom; Machida, Curtis A

    2016-01-01

    Acute apical abscesses are serious endodontic diseases resulting from pulpal infection with opportunistic oral microorganisms. The objective of this study was to identify and compare the oral microbiota in patients (N=18) exhibiting acute apical abscesses, originating from the demographic region in Portland, Oregon. The study hypothesis is that abscesses obtained from this demographic region may contain unique microorganisms not identified in specimens from other regions. Endodontic abscesses were sampled from patients at the Oregon Health & Science University (OHSU) School of Dentistry. DNA from abscess specimens was subjected to polymerase chain reaction amplification using 16S rRNA gene-specific primers and Cy3-dCTP labeling. Labeled DNA was then applied to microbial microarrays (280 species) generated by the Human Oral Microbial Identification Microarray Laboratory (Forsyth Institute, Cambridge, MA). The most prevalent microorganisms, found across multiple abscess specimens, include Fusobacterium nucleatum, Parvimonas micra, Megasphaera species clone CS025, Prevotella multisaccharivorax, Atopobium rimae, and Porphyromonas endodontalis. The most abundant microorganisms, found in highest numbers within individual abscesses, include F. nucleatum, P. micra, Streptococcus Cluster III, Solobacterium moorei, Streptococcus constellatus, and Porphyromonas endodontalis. Strong bacterial associations were identified between Prevotella multisaccharivorax, Acidaminococcaceae species clone DM071, Megasphaera species clone CS025, Actinomyces species clone EP053, and Streptococcus cristatus (all with Spearman coefficients >0.9). Cultivable and uncultivable bacterial species have been identified in endodontic abscesses obtained from the Portland, Oregon demographic region, and taxa identifications correlated well with other published studies, with the exception of Treponema and Streptococcus cristae, which were not commonly identified in endodontic abscesses between the

  17. Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2016-01-01

    Full Text Available Introduction: Acute myeloid leukemia (AML in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m 2 . The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61-86 years with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6. Males had median OS of 7 months (95% CI: 5.4-8.6 versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008. There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities.

  18. In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jason Joon Bock; Choi, Jin Hyun; Lee, Ik Jae; Park, Kwang Woo; Kim, Kang Pyo; Kim, Jun Won [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ahn, Sung Gwe; Jeong, Joon [Dept. of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.

  19. Chemical characterisation of Piper amalago (Piperaceae) essential oil by comprehensive two-dimensional gas chromatography coupled with rapid-scanning quadrupole mass spectrometry (GC×GC/qMS) and their antilithiasic activity and acute toxicity.

    Science.gov (United States)

    Dos Santos, Anaí L; Novaes, Antônio da Silva; Polidoro, Allan Dos S; de Barros, Márcio Eduardo; Mota, Jonas S; Lima, Daiane B M; Krause, Laiza C; Cardoso, Cláudia A L; Jacques, Rosângela A; Caramão, Elina B

    2018-02-26

    Piper amalago has a distribution from Mexico to Brazil; their aerial parts have been used in folk medicine to treat diuretic and kidney diseases. The purpose of this study was to obtain a deeper understanding of the chemical composition of essential oils (EOs) extracted from both the leaves and stems of P. amalago, compare them, and evaluate their antilithiasic activity and acute toxicity. Extraction was performed by hydrodistillation, whereas chemical characterisation by two-dimensional gas chromatography coupled with rapid-scanning quadrupole mass spectrometry (GC×GC/qMS). The antilithiasic activity was evaluated by the effect of the EOs on calcium oxalate crystallisation in vitro. The turbidity index and the number of crystals formed were determined and used as an estimative of the activity. In the acute toxicity assay, the effects of a single oral dose of the EOs in Wistar rats were determined. General behaviour, adverse effects, and mortality were determined. A total of 322 compounds were identified in the EOs. The sesquiterpenes displayed the highest contribution in leaves EOs among which included bicyclogermacrene and δ-cadinene. Sesquiterpenes and oxygenated sesquiterpenes displayed the highest contribution in EOs from stems, among which included bicyclogermacrene and α-cadinol. The EOs demonstrated an excellent action on the crystals growth inhibition, and the oral dose tested did not induce significant changes in the parameters for acute toxicity. The oils have a high chemical complexity, and there are differences between their compositions, which could explain the observed differences in antilithiasic activity. The findings support the use of this plant in folk medicine to treat kidney diseases. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Xie Shuyu

    2011-11-01

    Full Text Available Abstract Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50 was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the

  1. Oral glutamate intake reduces acute and chronic effects of ethanol in ...

    African Journals Online (AJOL)

    treatment, male Wistar rats were trained to consume ethanol-sucrose solution during a 2-h period daily, ... Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of ethanol. ..... glutamate release in the prefrontal cortex-NAc.

  2. Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Katoh, Hiroyuki; Noda, Shin-ei; Ito, Kazuto; Yamamoto, Takumi; Kashiwagi, Bunzo; Nakano, Takashi

    2005-01-01

    Purpose: We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. Methods and Materials: Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization

  3. Manual and oral apraxia in acute stroke, frequency and influence on functional outcome: The Copenhagen Stroke Study.

    Science.gov (United States)

    Pedersen, P M; Jørgensen, H S; Kammersgaard, L P; Nakayama, H; Raaschou, H O; Olsen, T S

    2001-09-01

    To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome. Seven hundred seventy six unselected, acute stroke patients who were admitted within seven days of stroke onset with unimpaired consciousness were included. If possible, the patients were assessed for manual and oral apraxia on acute admission. Neurologic stroke severity including aphasia was assessed with the Scandinavian Stroke Scale, and activities of daily living function was assessed with the Barthel Index. All patients completed their rehabilitation in the same large stroke unit. Six hundred eighteen patients could cooperate with the apraxia assessments. Manual apraxia was found in 7% of subjects (10% in left and 4% in right hemispheric stroke; chi2 = 9.0; P = 0.003). Oral apraxia was found in 6% (9% in left and 4% in right hemispheric stroke; chi2 = 5.4; P = 0.02). Both manual and oral apraxia were related to increasing stroke severity, and manual, but not oral, apraxia was associated with increasing age. There was no gender difference in frequency of apraxia. Patients with either type of apraxia had temporal lobe involvement more often than patients without. When analyzed with multiple linear and logistic regression analyses, neither manual nor oral apraxia had any independent influence on functional outcome. Apraxia is significantly less frequent in unselected patients with acute stroke than has previously been assumed and has no independent negative influence on functional outcome.

  4. Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

    DEFF Research Database (Denmark)

    Appelt, Ane L.; Bentzen, Søren M.; Jakobsen, Anders

    2015-01-01

    BACKGROUND: Long-course preoperative chemoradiotherapy (chemo-RT) improves outcomes for rectal cancer patients, but acute side effects during treatment may cause considerable patient discomfort and may compromise treatment compliance. We developed a dose-response model for acute urinary toxicity...... based on a large, single-institution series. MATERIAL AND METHODS: In total 345 patients were treated with (chemo-)RT for primary rectal cancer from January 2007 to May 2012. Urinary toxicity during RT was scored prospectively using the CTCAE v 3.0 cystitis score (grade 0-5). Clinical variables...... and radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above...

  5. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Waal, R.I.F. van der; Waal, I. van der [Univ. Hospital Vrije Univ., Dept. of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam (Netherlands); Veerman, A.J.P. [Univ. Hospital Vrije Univ., Dept. of Paediatric Oncology, Amsterdam (Netherlands); Snow, G.B. [Univ. Hospital Vrije Univ., Dept. of Otorhinolaryngology, Amsterdam (Netherlands)

    1997-02-01

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs.

  6. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Waal, R.I.F. van der; Waal, I. van der; Veerman, A.J.P.; Snow, G.B.

    1997-01-01

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs

  7. Effect of some drugs on radioprotective effectiveness, toxicity and distribution of 35S-Aminopropyl-aminoethyl-thiophosphate orally administered to mice

    International Nuclear Information System (INIS)

    Grechka, I.I.; Belavina, L.P.; Kalistpatov, G.V.; Zherebchenko, P.G.

    1979-01-01

    Studied was the influence of adreno- adn cholinolytics and cholinomimetic substances on radioprotective effectiveness and toxicity of aminopropyl-aminoehtyl-thiophosphate (APAETP) and distribution thereof among organs after oral and intraperitoneal administration. Atropine and INPEA decrease the toxicity and radioprotectiVe efficiency of APAETP when administered orally and do not influence these properties after intraperitoneal in ection. Deposition of the labelled radioprotector within the organs after oral administration is also indicative that atropine and INPEA can delay the transfer of APAETP from the stomach to the intenstine

  8. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy.

    Science.gov (United States)

    Mei, Lin; Ontiveros, Evelena P; Griffiths, Elizabeth A; Thompson, James E; Wang, Eunice S; Wetzler, Meir

    2015-07-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Striecker, Thorbjoern; Kessel, Kerstin [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Sterzing, Florian [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Habl, Gregor [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Edler, Lutz [Department of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Debus, Juergen [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany); Department of Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg (Germany); Herfarth, Klaus [Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg (Germany)

    2014-11-15

    Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

  10. Acute embryo toxicity and teratogenicity of three potential biofuels also used as flavor or solvent

    Energy Technology Data Exchange (ETDEWEB)

    Bluhm, Kerstin; Seiler, Thomas-Benjamin [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Anders, Nico [RWTH Aachen University, Aachener Verfahrenstechnik — Enzyme Process Technology, Worringerweg 1, 52074 Aachen (Germany); Klankermayer, Jürgen [RWTH Aachen University, Institut für Technische und Makromolekulare Chemie, Worringerweg 1, 52074 Aachen (Germany); Schaeffer, Andreas [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Hollert, Henner, E-mail: Henner.Hollert@bio5.rwth-aachen.de [RWTH Aachen University, Institute for Environmental Research, Worringerweg 1, 52074 Aachen (Germany); Chongqing University, College of Resources and Environmental Science, Chongqing 400715 (China); Nanjing University, State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing 210093 (China); Tongji University, College of Environmental Science and Engineering and State Key Laboratory of Pollution Control and Resource Reuse, Shanghai 200092 (China)

    2016-10-01

    The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC{sub 50}: 83 mg/L) compared to 2-MTHF (LC{sub 50}: 2980 mg/L), 2-MF (LC{sub 50}: 405 mg/L) and water accommodated fractions of the reference fuels including gasoline (LC{sub 50}: 244 mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. - Highlights: • The demand for biofuels increases but their (eco)toxicological effects are unknown. • Acute fish embryo toxicity and teratogenicity of potential biofuels were evaluated. • Ethyl levulinate induced a higher acute toxicity compared to WAFs of gasoline. • Ethyl levulinate caused

  11. Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Seol-Hee Moon

    Full Text Available A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study. Keywords: γ-Oryznaol, Rice, Rat, Repeated-dose oral toxicity study, NOAEL

  12. Sub-acute toxicity and biochemical effects of extracts of Anaphe ...

    African Journals Online (AJOL)

    Ataxia syndrome which is characterized by sudden onset of severe muscular tremor and gait ataxia has been shown to be associated with the consumption of the larvae of Anaphe venata in South Western part of Nigeria. In this report, the sub -acute toxicity and biochemical effects of polar and nonpolar extracts of Anaphe ...

  13. Whole acute toxicity removal from industrial and domestic effluents treated by electron beam radiation: emphasis on anionic surfactants

    International Nuclear Information System (INIS)

    Moraes, M.C.F.; Romanelli, M.F; Sena, H.C.; Pasqualini da Silva, G.; Sampa, M.H.O.; Borrely, S.I.

    2004-01-01

    Electron beam radiation has been applied to improve real industrial and domestic effluents received by Suzano wastewater treatment plant. Radiation efficacy has been evaluated as toxicity reduction, using two biological assays. Three sites were sampled and submitted for toxicity assays, anionic surfactant determination and electron beam irradiation. This paper shows the reduction of acute toxicity for both test-organisms, the marine bacteria Vibrio fischeri and the crustacean Daphnia similis. The raw toxic effluents exibitted from 0.6 ppm up to 11.67 ppm for anionic surfactant before being treated by the electron beam. Radiation processing resulted in reduction of the acute toxicity as well as surfactant removal. The final biological effluent was in general less toxic than other sites but the presence of anionic surfactants was evidenced

  14. Whole acute toxicity removal from industrial and domestic effluents treated by electron beam radiation: emphasis on anionic surfactants

    Energy Technology Data Exchange (ETDEWEB)

    Moraes, M.C.F. E-mail: mariacristinafm@uol.com.br; Romanelli, M.F; Sena, H.C.; Pasqualini da Silva, G.; Sampa, M.H.O.; Borrely, S.I

    2004-10-01

    Electron beam radiation has been applied to improve real industrial and domestic effluents received by Suzano wastewater treatment plant. Radiation efficacy has been evaluated as toxicity reduction, using two biological assays. Three sites were sampled and submitted for toxicity assays, anionic surfactant determination and electron beam irradiation. This paper shows the reduction of acute toxicity for both test-organisms, the marine bacteria Vibrio fischeri and the crustacean Daphnia similis. The raw toxic effluents exibitted from 0.6 ppm up to 11.67 ppm for anionic surfactant before being treated by the electron beam. Radiation processing resulted in reduction of the acute toxicity as well as surfactant removal. The final biological effluent was in general less toxic than other sites but the presence of anionic surfactants was evidenced.

  15. Acute toxicity of double-walled carbon nanotubes to three aquatic organisms

    CSIR Research Space (South Africa)

    Lukhele, LP

    2015-01-01

    Full Text Available , respectively. In the presence of humic acid high DWCNTs acute toxicity towards D. pulex and P. reticulata was observed but ionic strength led to opposite effect irrespective of DWCNTs form. Both humic acid and ionic strength shielded the P. subcapitata from...

  16. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  17. The Acute Toxicity and Hematological Characterization of the Effects of Tentacle-Only Extract from the Jellyfish Cyanea capillata

    Directory of Open Access Journals (Sweden)

    Liming Zhang

    2011-03-01

    Full Text Available To investigate the hematologic changes and the activities of jellyfish venoms other than hemolytic and cardiovascular toxicities, the acute toxicity of tentacle-only extract (TOE from the jellyfish Cyanea capillata was observed in mice, and hematological indexes were examined in rats. The median lethal dose (LD50 of TOE was 4.25 mg/kg, and the acute toxicity involved both heart- and nervous system-related symptoms. Arterial blood gas indexes, including pH, PCO2, HCO3−, HCO3std, TCO2, BEecf and BE (B, decreased significantly. PO2 showed a slight increase, while SO2c (% had no change at any time. Na+ and Ca2+ decreased, but K+ increased. Biochemical indexes, including LDH, CK, CK-MB, ALT, AST and sCr, significantly increased. Other biochemical indexes, including BUN and hemodiastase, remained normal. Lactic acid significantly increased, while glucose, Hct% and THbc showed slight temporary increases and then returned to normal. These results on the acute toxicity and hematological changes should improve our understanding of the in vivo pathophysiological effects of TOE from C. capillata and indicate that it may also have neurotoxicity, liver toxicity and muscular toxicity in addition to hemolytic and cardiovascular toxicities, but no kidney or pancreatic toxicity.

  18. Acute fibrinous organising pneumonia: a manifestation of trimethoprim-sulfamethoxazole pulmonary toxicity.

    Science.gov (United States)

    Jamous, Fady; Ayaz, Syed Zain; Choate, Jacquelyn

    2014-10-29

    A 50-year-old man was treated with trimethoprim-sulfamethoxazole (TMP-SMX) for acute arthritis of his right big toe. Within a few days, he developed dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. Symptoms improved with discontinuation of the antibiotic but worsened again with its reintroduction. An open lung biopsy was performed. We describe the workup performed and the factors that pointed to a final diagnosis of TMP-SMX-related pulmonary toxicity in the form of acute fibrinous organising pneumonia. 2014 BMJ Publishing Group Ltd.

  19. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    Science.gov (United States)

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  20. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    DAYANE K.D. NASCIMENTO

    2016-01-01

    Full Text Available ABSTRACT Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE. The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  1. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.3

    Science.gov (United States)

    Information on the acute toxicity to multiple species is needed for the assessment of the risks to, and the protection of, individuals, populations, and ecological communities. However, toxicity data are limited for the majority of species, while standard test species are general...

  2. Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH).

    NARCIS (Netherlands)

    Sobanska, Marta; Scholz, Stefan; Nyman, Anna-Maija; Cesnaitis, Romanas; Gutierrez Alonso, Simon; Klüver, Nils; Kühne, Ralph; Tyle, Henrik; de Knecht, Joop; Dang, Zhichao; Lundbergh, Ivar; Carlon, Claudio; De Coen, Wim

    In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity

  3. Guidance for Reviewing OCSPP 850.2100 Avian Oral Toxicity Studies Conducted with Passerine Birds

    Science.gov (United States)

    Guidance based on comparison of results from the TG223 validation studies to results from avian acute oral studies previously submitted to EPA for two test chemicals following EPA's 850.2100 (public draft) guidelines.

  4. ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

    Science.gov (United States)

    Walker, Calvin C., James T. Winstead, Steven S. Foss, Janis C. Kurtz, James Watts, Jeanne E. Scott and William S. Fisher. In press. Acute and Chronic Toxicity of Brevetoxin to Oysters and Grass Shrimp (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November ...

  5. Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

    Science.gov (United States)

    Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

    2011-11-01

    Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios.

  6. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

    Science.gov (United States)

    Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

    2013-01-01

    The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

  7. Acute and chronic systemic chromium toxicity.

    Science.gov (United States)

    Gad, S C

    1989-10-01

    Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

  8. Reduction of acute toxicity of the pharmaceutical fluoxetine (Prozac) submitted to ionizing radiation to Vibrio fischeri

    International Nuclear Information System (INIS)

    Santos, Dymes R.A.; Garcia, Vanessa S.G.; Vilarrubia, Anna C.S.; Borrely, Sueli I.

    2011-01-01

    The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L -1 , 2.34 mg.L -1 , 2.35 mg.L -1 and 1.80 mg.L -1 , respectively, showing a notable reduction of the acute toxicity for this organism. (author)

  9. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    Science.gov (United States)

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

  10. Toxicity studies of the water extract from the calyces of Hibiscus ...

    African Journals Online (AJOL)

    Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and ...

  11. Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

    Science.gov (United States)

    Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

    2015-01-01

    Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or

  12. The acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ionic liquids on Chlorella vulgaris and Daphnia magna.

    Science.gov (United States)

    Zhang, Cheng; Zhang, Shuai; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong

    2017-10-01

    Given their increasingly widespread application, the toxic effects of ionic liquids (ILs) have become the subject of significant attention in recent years. Therefore, the present study assessed the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ([C n mim]NO 3 (n = 2, 4, 6, 8, 10, 12)) on Chlorella vulgaris and Daphnia magna. The sensitivity of the tested organism Daphnia magna and the investigated IL concentrations in water using high-performance liquid chromatography (HPLC) were also evaluated to demonstrate the reliability of the present study. The results illustrated that Daphnia magna is indeed sensitive to the reference toxicant and the investigated ILs were stable in the aquatic environment. The 50% effect concentration (EC 50 ) was used to represent the acute toxic effects on Chlorella vulgaris and Daphnia magna. With the increasing alkyl-chain lengths, the toxicity of the investigated ILs increased in both the test organisms. Accordingly, the alkyl-chain lengths can cause significantly toxic effects on aquatic organisms, and Daphnia magna are much more sensitive than Chlorella vulgaris to the imidazolium-based ILs used in the present study. Furthermore, the present study provides more information on the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. A prospective phase I/II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix - acute toxicity and biomarker response analysis

    International Nuclear Information System (INIS)

    Chan, P.; Doll, C.; Oza, A.; Pintilie, M.; Levin, W.; Manchul, L.; Fyles, A.; Milosevic, M.

    2003-01-01

    To evaluate the toxicity and biomarker response of celecoxib (C) as a biologic modifier in combination with definitive chemoradiotherapy (CRT) in women with cervix cancer. Fifteen cervix patients were entered into the first phase of this prospective study between March 2001 and January 2002. FIGO stages included IB(2), IIB(8), IIIB(4), and IVA(1), and median age was 51 years (range 26-62). Celecoxib 400mg orally was given b.i.d. 2 weeks prior to, and during the CRT. Toxicity assessments were performed weekly up to 12 weeks following treatment prior to further accrual using the NCIC-CTC. Hypoxia (HP5) and interstitial fluid pressure (IFP) assays were performed at day 0 and 14. Eleven patients completed the prescribed therapy. Only 2 of 4 patients discontinued C due to GI toxicity. In total there were 6 (40%) with grade 3/4 acute toxicity. Four were related to GI, one to skin reaction while the other was haematological. Although it was difficult to distinguish CRT toxicity from C, the proportion of patients with severe acute toxicity was similar to what we previously reported with CRT alone (8/24 (33%), Rodrigues, IJROBP 2001:Vol 51:(3): (Supp 1): 334). GI toxicity was more common in this study whereas haematologic effects were more frequent in the previous study. Evaluating the most recent measurable data set, 6 of 16 patients showed a decrease in HP5, (3.8 - 89.7%) while 10 of 14 patients had a reduction in IFP, (1.3 - 16.2mmHg). Two grade 4 late GI toxicity developed. Celecoxib is tolerated by patients receiving CRT for cervix cancer. Response of microenvironmental biomarkers to C was seen in the majority, suggesting a role as early markers of treatment outcome. Further follow-up is needed to assess the risk of late toxicity. The trial has been re-opened with C reduced to 300 mg b.i.d

  14. Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Santos, Adriana; Martins, Lidiane C; Weltman, Eduardo; Chen, Michael J; Sakuraba, Roberto; Lopes, Cleverson P; Cruz, José C

    2010-01-01

    This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups

  15. Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

    Science.gov (United States)

    Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

    2011-05-01

    From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

  16. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    Directory of Open Access Journals (Sweden)

    Gui Mi Ko

    2010-06-01

    Full Text Available In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme of the Federal University of São Paulo (UNIFESP: 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995, 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%, chemicals used in industry (32.9%, plastics, rubber, and other polymers (15.9%, agrotoxics (4.0%, medicines (2.7%, and vaccines (2.5%. In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.Descrevemos os testes usados em ensaios biológicos de curta duração para estudo de toxicidade e inocuidade de cosméticos, fármacos e outras substâncias químicas, feitos no Biotério Central/Cedeme da Unifesp, de 1986 a 2000. Testamos 602 amostras nos seguintes ensaios: 385 de irritação cutânea, 90 de irritação ocular (até 1995, 31 de toxicidade sistêmica por injeção, 26 de toxicidade oral aguda, 15 de toxicidade por aplicação intracutânea, 15 de sensibilização da pele, 15 de toxicidade de soros e vacinas de uso humano, 14 de toxicidade por implantação intramuscular, 7 de pirogênio, 2 de toxicidade dérmica aguda e

  17. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    Science.gov (United States)

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

  18. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    Science.gov (United States)

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATIONMichael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  19. Acute toxicity of ammonia to blue tilapia, Oreochromis aureus in ...

    African Journals Online (AJOL)

    The acute toxicity of blue tilapia, Oreochromis aureus (3.28 ± 0.36 g in body weight, 61.84 ± 2.08 mm in body length) exposed to environmental un-ionized ammonia at different salinities (1, 8, 12, 16 and 20 ppt) was assessed via a series of static exposure trials. Median lethal concentrations of 24 h of exposure were ...

  20. Acute Toxicity of Delsate® Herbicide (Glyphosate) On Albumin and ...

    African Journals Online (AJOL)

    Some biochemical metabolism [albumin and blood urea nitrogen (BUN)] were monitored in the serum of fresh water adult African Catfish, Clarias gariepinus exposed to acute concentrations of Delsate herbicide for 96 hours. The concentrations of the toxicant tested were 0.5 mgL-1, 1.0 mgL-1, 1.5 mgL-1, 2.0 mgL-1 and 2.5 ...

  1. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  2. Oral health and orofacial pain in people with dementia admitted to acute hospital wards: observational cohort study.

    Science.gov (United States)

    van de Rijt, Liza J M; Weijenberg, Roxane A F; Feast, Alexandra R; Vickerstaff, Victoria; Lobbezoo, Frank; Sampson, Elizabeth L

    2018-05-23

    Orofacial pain in people with dementia is difficult to detect, and often under-treated. Our aim was to investigate the prevalence of orofacial pain in people with dementia in acute hospitals in the UK. Secondary aims were to examine oral health status and explore associations between orofacial pain and oral health factors. This cross-sectional observational study was carried out in two UK hospitals. Using the Orofacial Pain Scale in Non-Verbal Individuals (OPS-NVI) to identify orofacial pain, 101 participants with dementia, admitted to acute medical wards, were observed for at least 3 min during rest and chewing. Verbal participants were then asked about presence of orofacial pain, using self-report pain scales. Finally, a brief oral assessment was performed. Orofacial pain, assessed with the OPS-NVI, was present in 11.9% (95% C.I. 5.9, 18.8) of participants at rest and 21.9% (95% C.I. 14.6, 31.3) whilst chewing. Participants who were no longer able to self-report pain were significantly more likely to experience orofacial pain. Oral health in both dentate and edentate participants was poor. Brush frequency, indication of chewing quality, consistency of the food, presence of extra-oral abnormalities, person who performed mouth care, and oral hygiene in dentate participants were significant predictors for the presence of orofacial pain. Improving oral care in acute hospital patients with dementia, particularly those who cannot self-report pain, may significantly reduce pain and suffering in this population.

  3. Acute Toxicity Effect of the Leaf Extract of Leptadenia Hastata (Pers ...

    African Journals Online (AJOL)

    ... the LD50 of the aqueous extract of the Leptadenia hastata was calculated using arithmetic method. The acute toxicity signs observed were inappetence, weakness, unsteady gait, polypnoea and asthenia in all the groups; having unsteady gait and polypnoea being more prominent in 800 to 3200mg/Kg bwt treated groups.

  4. Oral Fosfomycin for the Treatment of Acute and Chronic Bacterial Prostatitis Caused by Multidrug-Resistant Escherichia coli

    Directory of Open Access Journals (Sweden)

    George G. Zhanel

    2018-01-01

    Full Text Available Acute and chronic bacterial prostatitis in outpatients is commonly treated with oral fluoroquinolones; however, the worldwide dissemination of multidrug-resistant (MDR Escherichia coli has resulted in therapeutic failures with fluoroquinolones. We reviewed the literature regarding the use of oral fosfomycin in the treatment of acute and chronic prostatitis caused by MDR E. coli. All English-language references on PubMed from 1986 to June 2017, inclusive, were reviewed from the search “fosfomycin prostatitis.” Fosfomycin demonstrates potent in vitro activity against a variety of antimicrobial-resistant E. coli genotypes/phenotypes including ciprofloxacin-resistant, trimethoprim-sulfamethoxazole-resistant, extended-spectrum β-lactamase- (ESBL- producing, and MDR isolates. Fosfomycin attains therapeutic concentrations (≥4 μg/g in uninflamed prostatic tissue and maintains a high prostate/plasma ratio up to 17 hours after oral administration. Oral fosfomycin’s clinical cure rates in the treatment of bacterial prostatitis caused by antimicrobial-resistant E. coli ranged from 50 to 77% with microbiological eradication rates of >50%. An oral regimen of fosfomycin tromethamine of 3 g·q 24 h for one week followed by 3 g·q 48 h for a total treatment duration of 6–12 weeks appeared to be effective. Oral fosfomycin may represent an efficacious and safe treatment for acute and chronic prostatitis caused by MDR E. coli.

  5. Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Amsbaugh, Mark J. [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Grosshans, David R., E-mail: dgrossha@mdanderson.org [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-01

    Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

  6. Photographic documentation of acute radiation-induced side effects of the oral mucosa

    International Nuclear Information System (INIS)

    Riesenbeck, D.; Doerr, W.; Feyerabend, T.; Richter, E.; Fietkau, R.; Henne, K.; Schendera, A.

    1998-01-01

    Background: Radiotherapy in cancer of the head and neck induces cutaneous and mucosal reactions. These must be carefully assessed and documented to control the accuracy of individual treatment, the overall toxicity of particular treatment schedules, the efficacy of prophylaxis and treatment and to determine the adequate therapy of treatment sequelae depending on the severity of the reactions. The accurate classification of lesions according to internationally accepted schedules (WHO/RTOG/CTC) is indispensable for the comparison of radiotherapy treatment results and efficacy of supportive care. Methods: While the treatment of cancer depends on tumor stage and medical circumstances of the patient and is more or less standardized, prophylaxis and treatment of side-effects is highly variable. Discussing an optimized prophylaxis and therapy of oral mucositis, the problem of accurate classification and documentation emerged. The verbal description of mucosal lesions is open to many subjective interpretations. Photographic documentation seems a suitable method to optimize the grading of toxicity. Results: A photographic survey of typical lesions for each grade of toxicity is a tool to reach several aims in one step. Toxicity of an individual patient may be compared with representative photographic examples in daily routine to decide quickly on the grade of toxicity. Subjective differences due to intra- and interpersonal variability of the evaluating radiooncologist will be reduced. The efficacy of trof treatment can be proven by accurate documentation. Randomized clinical studies concerning prophylaxis and treatmen mucositis will provide more reliable results if evaluation of toxicity grading is standardized by photographs. Conclusions: Photographic documentation of lesions of the oral mucosa might be the best means to reduce interindividual subjectivity in grading. It is a valuable appendix to standard classification systems and only concerns the visible signs of mucosal

  7. Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

    Science.gov (United States)

    Wei, Li; Shao, Wei-Wei; Ding, Guo-Hua; Fan, Xiao-Li; Yu, Miao-Ling; Lin, Zhi-Hua

    2014-07-01

    We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

  8. Sub-Acute Hepatoxicity of Aqueous Leaf Extract of Eucalyptus ...

    African Journals Online (AJOL)

    Sub–acute toxicity study of the aqueous leaf extract of Eucalyptus camaldulensis was carried out on albino rats. Doses of 250mg, 500mg, 750mg and 1000mg per kilogram body weight of the extract were administered orally for 21 days. The activities of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), ...

  9. The acute toxicity of ethanol extract from irradiated Temulawak (curcuma xanthorrizha roxb.) which have anticancer activity

    International Nuclear Information System (INIS)

    Ermin Katrin; Susanto; Hendig Winarno

    2011-01-01

    Pasteurization of herbs and herbal medicinal products have been carried out by several herbal industries, but information about the safety of irradiated herbal medicine is still a little, even the influence of gamma irradiation for pasteurization purpose on the toxicity of crude Temulawak has never been investigated. The ethanol extract of Curcuma xanthorrizha Roxb. has cytotoxic activity which potential as an anticancer. In this research, the acute toxicity tests were carried out to the ethanol extract from Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy. The acute toxicity tests of ethanol extract were conducted in mice by observing the effect of extracts on animal behavior (pharmacologic profile) after a single dose of test material, the development of animal body weight and death every day for 14 days and observed several organ weights on day 14. Acute toxicity test results after administration of extracts on male and female mice a dose up to 7500 mg/kg body weight (BW) showed that no deaths and no significant toxic effect, so that the ethanol extract of Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy can be declared safe. Thus LD 50 from ethanol extract of Curcuma xanthorrizha without irradiation and irradiated (5 and 10 kGY) in mice was greater than 7500 mg/kg body weight. (author)

  10. Small Microbial Three-Electrode Cell Based Biosensor for Online Detection of Acute Water Toxicity.

    Science.gov (United States)

    Yu, Dengbin; Zhai, Junfeng; Liu, Changyu; Zhang, Xueping; Bai, Lu; Wang, Yizhe; Dong, Shaojun

    2017-11-22

    The monitoring of toxicity of water is very important to estimate the safety of drinking water and the level of water pollution. Herein, a small microbial three-electrode cell (M3C) biosensor filled with polystyrene particles was proposed for online monitoring of the acute water toxicity. The peak current of the biosensor related with the performance of the bioanode was regarded as the toxicity indicator, and thus the acute water toxicity could be determined in terms of inhibition ratio by comparing the peak current obtained with water sample to that obtained with nontoxic standard water. The incorporation of polystyrene particles in the electrochemical cell not only reduced the volume of the samples used, but also improved the sensitivity of the biosensor. Experimental conditions including washing time with PBS and the concentration of sodium acetate solution were optimized. The stability of the M3C biosensor under optimal conditions was also investigated. The M3C biosensor was further examined by formaldehyde at the concentration of 0.01%, 0.03%, and 0.05% (v/v), and the corresponding inhibition ratios were 14.6%, 21.6%, and 36.4%, respectively. This work provides a new insight into the development of an online toxicity detector based on M3C biosensor.

  11. Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

    International Nuclear Information System (INIS)

    Sherry, J.; Scott, B.; Dutka, B.

    1997-01-01

    The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents

  12. Acute and sub-chronic oral toxicity studies of the extracts from herbs ...

    African Journals Online (AJOL)

    AJL

    2012-06-14

    Jun 14, 2012 ... Thailand registered PN in the list of herbal medical ... Pharmacy, Silpakorn University, Nakorn Pathom, Thailand. The ... automated blood analyzer (Hitachi Science Systems Ltd., Ibaraki, ..... toxic effects of the extracts in both concurrent control and ..... uric acid levels might be necessary when patients are.

  13. Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression.

    Science.gov (United States)

    Bevan, Melody G; Asrani, Varsha M; Bharmal, Sakina; Wu, Landy M; Windsor, John A; Petrov, Maxim S

    2017-06-01

    Tolerance of oral food is an important criterion for hospital discharge in patients with acute pancreatitis. Patients who develop oral feeding intolerance have prolonged hospitalisation, use additional healthcare resources, and have impaired quality of life. This study aimed to quantify the incidence of oral feeding intolerance, the effect of confounders, and determine the best predictors of oral feeding intolerance. Clinical studies indexed in three electronic databases (EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials) were reviewed. Incidence and predictor data were meta-analysed and possible confounders were investigated by meta-regression analysis. A total of 22 studies with 2024 patients met the inclusion criteria, 17 of which (with 1550 patients) were suitable for meta-analysis. The incidence of oral feeding intolerance was 16.3%, and was not affected by WHO region, age, sex, or aetiology of acute pancreatitis. Nine of the 22 studies investigated a total of 62 different predictors of oral feeding intolerance. Serum lipase level prior to refeeding, pleural effusions, (peri)pancreatic collections, Ranson score, and Balthazar score were found to be statistically significant in meta-analyses. Oral feeding intolerance affects approximately 1 in 6 patients with acute pancreatitis. Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  14. Assessment of acute toxicity of water soluble fraction of diesel on ...

    African Journals Online (AJOL)

    Acute toxicity of water soluble fraction (WSF) of diesel fuel was assessed by evaluating its effects on growth of two marine microalgae, Isochrysis and Chaetoceros. Pure cultures of each of the two microalgae were exposed to concentrations of 0% (controls), 5%, 10%, 15% and 20% of diesel WSF (in triplicates) and allowed ...

  15. Acute Toxicity of Castor Oil Bean Extract and Tolerance Level of ...

    African Journals Online (AJOL)

    The experiment was carried out to determine the acute toxicity of raw castor oil bean (Ricinus communis) extract and the tolerance level of raw castor oil bean by broilers. The seeds were ground, defatted with petroleum ether and the residue was subjected to extraction with phosphate-buffered saline. The extract volume ...

  16. Acute Oral Toxicity of DIGL-RP Solid Propellant in Sprague-Dawley Rats

    Science.gov (United States)

    1989-11-30

    protein droplet and cast formation, glomeruli and cortical tubules Liver--diffuse vacuolation Stomach--multifocal, acute, necrotizing gastritis ...The choice of tissues examined histologically was biased by gross evaluation. Indications of renal protein loss were noted in five animals (casts and

  17. Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

    Science.gov (United States)

    Johnson, W. Waynon; Finley, Mack T.

    1980-01-01

    Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

  18. Reduction of acute toxicity of the pharmaceutical fluoxetine (Prozac) submitted to ionizing radiation to Vibrio fischeri

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Dymes R.A.; Garcia, Vanessa S.G.; Vilarrubia, Anna C.S.; Borrely, Sueli I., E-mail: vanessagarcia@usp.br, E-mail: sborrely@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L{sup -1}, 2.34 mg.L{sup -1}, 2.35 mg.L{sup -1} and 1.80 mg.L{sup -1}, respectively, showing a notable reduction of the acute toxicity for this organism. (author)

  19. Comparative acute toxicity of neonicotinoid and pyrethroid insecticides to non-target crayfish (Procambarus clarkii) associated with rice-crayfish crop rotations.

    Science.gov (United States)

    Barbee, Gary C; Stout, Michael J

    2009-11-01

    Most insecticides used to control rice water weevil (Lissorhoptrus oryzophilus Kuscel) infestations are pyrethroids. However, pyrethroids are highly toxic to non-target crayfish associated with rice-crayfish crop rotations. One solution to the near-exclusive reliance on pyrethroids in a rice-crayfish pest management program is to incorporate neonicotinoid insecticides, which are insect specific and effective against weevils but not extremely toxic to crayfish. This study aimed to take the first step to assess neonicotinoids as alternatives to pyrethroids in rice-crayfish crop rotations by measuring the acute toxicities of three candidate neonicotinoid insecticides, clothianidin, dinotefuran and thiamethoxam, to juvenile Procambarus clarkii (Girard) crayfish and comparing them with the acute toxicities of two currently used pyrethroid insecticides, lambda-cyhalothrin and etofenprox. Neonicotinoid insecticides are at least 2-3 orders of magnitude less acutely toxic (96 h LC(50)) than pyrethroids to juvenile Procambarid crayfish: lambda-cyhalothrin (0.16 microg AI L(-1)) = etofenprox (0.29 microg AI L(-1)) > clothianidin (59 microg AI L(-1)) > thiamethoxam (967 microg AI L(-1)) > dinotefuran (2032 microg AI L(-1)). Neonicotinoid insecticides appear to be much less hazardous alternatives to pyrethroids in rice-crayfish crop rotations. Further field-level neonicotinoid acute and chronic toxicity testing with crayfish is needed. (c) 2009 Society of Chemical Industry.

  20. Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

    Science.gov (United States)

    Tao, Zhenchao; Gao, Jin; Qian, Liting; Huang, Yifan; Zhou, Yan; Yang, Liping; He, Jian; Yang, Jing; Wang, Ru; Zhang, Yangyang

    2017-12-01

    To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2-4) and minimum reaction (grades 0-1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  1. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

    Science.gov (United States)

    Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

    2008-01-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

  2. Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

    International Nuclear Information System (INIS)

    Rebagay, T.V.; Dodd, D.A.; Lockrem, L.L.; Voogd, J.A.

    1993-01-01

    Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years operation of the Hanford Site of the US Department of Energy near Richland, Washington. The current strategy for the disposal of the low-level radioactive portion of these wastes involves immobilization of the waste in the form of grout. Because the potential risk of animal and plant exposure to grouts is unknown, acute toxicity screening of grouts is needed. Grouts were prepared by mixing a surrogate nonradioactive liquid waste with a blend consisting of cement, fly ash, and clay. Aqueous extracts of the grout were then screened for acute toxicity using aquatic invertebrates as test organisms and a fluorogenic substrate as the toxic stress indicator. After a 1-hour exposure of juvenile daphnids (D, magna, D. pulex, and C. dubia) to the grout extracts followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The EC50 values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The slight difference in the responses may be attributed to the subjective pass-fail scoring of the fluorescence criterion. The results indicated that the grout studied is nonhazardous and nondangerous

  3. Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam. Merr. in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Muhammad Kifayatullah

    2015-10-01

    Conclusions: The result indicates that the oral administration of Pericampylus glaucus (Lam. Merr. extract did not produce any significant toxic effect in BALB/c mice. Hence, the extract can be utilized safely for therapeutic use in pharmaceutical formulations.

  4. Safety assessment of Uvaria chamae root extract: acute and ...

    African Journals Online (AJOL)

    Background: Uvaria chamae is a medicinal plant that is used in many parts of the world in the treatment of diabetes, and other diseases. However, research is needed to ascertain the beneficial and adverse effects of the consumption of the extract. In this study, we evaluated the acute and subchronic oral toxicity and safety ...

  5. Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice

    Institute of Scientific and Technical Information of China (English)

    Qixiao Zhai; Tianqi Li; Leilei Yu; Yue Xiao; Saisai Feng; Jiangping Wu; Jianxin Zhao; Hao Zhang; Wei Chen

    2017-01-01

    Oral exposure to toxic metals such as cadmium (Cd),lead (Pb),copper (Cu) and aluminum (Al) can induce various adverse health effects in humans and animals.However,the effects of these metals on the gut microbiota have received limited attention.The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner.Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice,whereas no significant changes were observed in groups treated with other metals.Cd exposure significantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae.Pb exposure significantly decreased the abundances of eight genera:unclassified and uncultured Ruminococcaceae,unclassified Lachnospiraceae,Ruminiclostridium_9,Rikenellaceae_RC9_gut_group,Oscillibacter,Anaerotruncus and Lachnoclostridium.Cu exposure affected abundances of the genera Alistipes,Bacteroides,Ruminococcaceae_UCG-014,Allobaculum,Mollicutes_RFg_norank,Rikenellaceae_RC9_gut_group,Ruminococcaceae_unclassified and Turicibacter.Al exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus.Exposure to any metal for eight weeks significantly decreased the abundance of Akkermansia.These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.

  6. Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

    International Nuclear Information System (INIS)

    Halton, D.M.

    1995-09-01

    In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC LO , LC 10 and LC 50 levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs

  7. Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

    Energy Technology Data Exchange (ETDEWEB)

    Halton, D M

    1995-09-01

    In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC{sub LO}, LC{sub 10} and LC{sub 50} levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs.

  8. Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine.

    Science.gov (United States)

    Arbo, M D; Larentis, E R; Linck, V M; Aboy, A L; Pimentel, A L; Henriques, A T; Dallegrave, E; Garcia, S C; Leal, M B; Limberger, R P

    2008-08-01

    Dietary supplements containing bitter orange unripe fruit extract/p-synephrine are consumed worldwide for lose weight. This study were conducted to determine the concentration of p-synephrine in unripe fruits and leaves from Citrus aurantium Lin, C. sinensis Osbeck, C. deliciosa Ten, C. limon Burm and C. limonia Osbeck, collected in Southern Brazil, and to evaluate the acute toxicity of C. aurantium extract and p-synephrine. A high performance liquid chromatographic method with diode array detector (HPLC-DAD) was optimized and validated for determination of p-synephrine. The results indicate that all of analyzed samples present p-synephrine in amounts that range from 0.012% to 0.099% in the unripe fruits and 0.029 to 0.438% in the leaves. Acute oral administration of C. aurantium extracts (2.5% p-synephrine, 300-5,000 mg/kg) in mice produced reduction of locomotor activity, p-synephrine (150-2,000 mg/kg) produced piloerection, gasping, salivation, exophtalmia and reduction in locomotor activity, which was confirmed in spontaneous locomotor activity test. All the effects were reversible and persisted for 3-4h. The toxic effects observed seem to be related with adrenergic stimulation and should alert for possible side effects of p-synephrine and C. aurantium.

  9. Cumulative toxicity of neonicotinoid insecticide mixtures to Chironomus dilutus under acute exposure scenarios.

    Science.gov (United States)

    Maloney, Erin M; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

    2017-11-01

    Extensive agricultural use of neonicotinoid insecticide products has resulted in the presence of neonicotinoid mixtures in surface waters worldwide. Although many aquatic insect species are known to be sensitive to neonicotinoids, the impact of neonicotinoid mixtures is poorly understood. In the present study, the cumulative toxicities of binary and ternary mixtures of select neonicotinoids (imidacloprid, clothianidin, and thiamethoxam) were characterized under acute (96-h) exposure scenarios using the larval midge Chironomus dilutus as a representative aquatic insect species. Using the MIXTOX approach, predictive parametric models were fitted and statistically compared with observed toxicity in subsequent mixture tests. Single-compound toxicity tests yielded median lethal concentration (LC50) values of 4.63, 5.93, and 55.34 μg/L for imidacloprid, clothianidin, and thiamethoxam, respectively. Because of the similar modes of action of neonicotinoids, concentration-additive cumulative mixture toxicity was the predicted model. However, we found that imidacloprid-clothianidin mixtures demonstrated response-additive dose-level-dependent synergism, clothianidin-thiamethoxam mixtures demonstrated concentration-additive synergism, and imidacloprid-thiamethoxam mixtures demonstrated response-additive dose-ratio-dependent synergism, with toxicity shifting from antagonism to synergism as the relative concentration of thiamethoxam increased. Imidacloprid-clothianidin-thiamethoxam ternary mixtures demonstrated response-additive synergism. These results indicate that, under acute exposure scenarios, the toxicity of neonicotinoid mixtures to C. dilutus cannot be predicted using the common assumption of additive joint activity. Indeed, the overarching trend of synergistic deviation emphasizes the need for further research into the ecotoxicological effects of neonicotinoid insecticide mixtures in field settings, the development of better toxicity models for neonicotinoid mixture

  10. Acute Toxicity of Justicia gendarussa Burm. Leaves

    Directory of Open Access Journals (Sweden)

    Juheini Amin

    2010-11-01

    Full Text Available Acute Toxicity of Justicia gendarussa Burm. Leaves. Preminelary experiment showed that ethanolic extract ofgandarusa leaves (Justicia gendarussa Burm. could decreased uric acid blood level on rats. The aim of this experimentwas to determine of the value LD50 and liver function based on activities of aminotransferase. Animals test which wereused in this experiment were 50 males and 50 females white mice. They were divided into 5 groups. Group 1 as controlgroup was given aquadest. Group 2-5 were treated by ethanolic extract of gandarusa leaves with dosage 4, 8, 16, and 32g/kg bw. The LD50 value was determined by the amount of death in group during 24 hours after giving a single dose oftest substance. The result showed that the highest dose was practically non toxic with LD50 value of 31.99 g/kg bw(male groups and 27.85 g/kg bw (female groups. Measurement of aminotransferase activity was done by usingcolorimetric method. The result of ANOVA analysis for liver function showed that the giving test substance 4 g/kg bw–16 g/kg bw was not significantly different between treated groups and control group.

  11. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    International Nuclear Information System (INIS)

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-01-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices

  12. Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

    2013-06-01

    In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

  13. Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients

    International Nuclear Information System (INIS)

    Tanimoto, Ryuta; Bekku, Kensuke; Katayama, Norihisa

    2013-01-01

    The objectives of this study were to describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On multivariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100. (author)

  14. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    Energy Technology Data Exchange (ETDEWEB)

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

  15. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

  16. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  17. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-01-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  18. Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity

    Directory of Open Access Journals (Sweden)

    Beltrán César

    2011-08-01

    Full Text Available Abstract Background Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. Methods In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. Results The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%, abdomen (17% and thorax (6%. The most prevalent histological types were: medulloblastoma (16 patients, neuroblastoma (9 patients and rhabdomyosarcoma (7 patients. A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72% were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy. In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6% of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6% had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases were significantly associated with severe toxicity (grade 3 or more, whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. Conclusion HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of

  19. Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity

    International Nuclear Information System (INIS)

    Mesbah, Latifa; Marsiglia, Hugo; Matute, Raúl; Usychkin, Sergey; Marrone, Immacolata; Puebla, Fernando; Mínguez, Cristina; García, Rafael; García, Graciela; Beltrán, César

    2011-01-01

    Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly

  20. Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

    Science.gov (United States)

    Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

    2017-09-01

    Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    Directory of Open Access Journals (Sweden)

    George Yang

    2015-06-01

    Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

  2. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  3. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

    2011-01-01

    BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving

  4. Diclofenac potassium powder for oral solution: a review of its use in patients with acute migraine.

    Science.gov (United States)

    Garnock-Jones, Karly P

    2014-08-01

    Diclofenac potassium powder for oral solution (Voltfast(®), Catafast(®), Cambia(®); hereafter referred to as diclofenac potassium powder) is a non-steroidal anti-inflammatory drug (NSAID), and is indicated for the acute treatment of migraine. This article reviews the pharmacological properties of diclofenac potassium powder and its efficacy and tolerability in patients with acute migraine. Diclofenac potassium powder was clinically efficacious and generally well tolerated in placebo-controlled trials in patients with this indication; it was more effective than diclofenac potassium tablets with regard to the primary endpoint of 2-h pain relief as well as in several important secondary endpoints, such as time to onset of analgesic action. The oral powder-for-solution formulation of diclofenac potassium is a useful option in the acute treatment of migraine with or without aura.

  5. Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

    International Nuclear Information System (INIS)

    Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

    2010-01-01

    2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

  6. A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

    Science.gov (United States)

    Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

    2011-12-01

    Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

  7. Acute and subacute toxicity of {sup 18}F-FDG; Toxicidade aguda e subaguda do radiofarmaco {sup 18}F-FDG

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Danielle Maia

    2013-07-01

    Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the {sup 18}F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of {sup 18}F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  8. Acute toxicity assessment of Osthol content in bio-pesticides using two aquatic organisms

    Directory of Open Access Journals (Sweden)

    Eun-Chae Yim

    2014-12-01

    Full Text Available Objectives This study focused on the assessment of acute toxicity caused by Osthol, a major component of environment-friendly biological pesticides, by using two aquatic organisms. Methods The assessment of acute toxicity caused by Osthol was conducted in Daphnia magna and by examining the morphological abnormalities in Danio rerio embryos. Results The median effective concentration value of Osthol in D. magna 48 hours after inoculation was 19.3 μM. The median lethal concentration of D. rerio embryo at 96 hours was 30.6 μM. No observed effect concentration and predicted no effect concentration values of Osthol in D. magna and D. rerio were calculated as 5.4 and 0.19 μM, respectively. There was an increase in the morphological abnormalities in D. rerio embryo due to Osthol over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation were observed in embryos at 24–48 hours. Symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects, and symptoms of collapse were observed in fertilized embryo tissue within 96 hours. Ocular defects and pigmentation were the additional symptoms observed in this study. Conclusions Because Osthol showed considerable toxicity levels continuous toxicity evaluation in agro-ecosystems is necessary when bio-pesticides containing Osthol are used.

  9. Acute Toxicity from Topical Cocaine for Epistaxis: Treatment with Labetalol.

    Science.gov (United States)

    Richards, John R; Laurin, Erik G; Tabish, Nabil; Lange, Richard A

    2017-03-01

    Topical cocaine is sometimes used for the treatment of epistaxis, as it has both potent anesthetic and vasoconstrictive properties. Cocaine has unpredictable cardiovascular effects, such as sudden hypertension, tachycardia, coronary arterial vasoconstriction, and dysrhythmia. We report a case of acute iatrogenic cardiovascular toxicity from the use of topical cocaine in a 56-year-old man presenting to the Emergency Department with profound epistaxis. To prepare for cauterization and nasal packing, the patient received 4% topical cocaine-soaked nasal pledgets. He became hypertensive, tachypneic, tachycardic, and dysphoric immediately after administration. To directly counter these adverse hyperadrenergic effects, the patient was given 10 mg intravenous labetalol, a mixed β- and α-blocker. This instantly normalized his vital signs and adverse subjective effects. His epistaxis was successfully treated, and he was discharged 1 h later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We believe that emergency physicians should be aware of the unpredictable acute cardiovascular toxicity of topical cocaine. Labetalol represents an effective first-line treatment, which, unlike benzodiazepines, directly counters the pharmacologic effects of cocaine and has no respiratory or sedative side effects. Labetalol, with its mixed β/α-blocking properties, also mitigates the potential for "unopposed α-stimulation." Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma. A report on acute toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Norkus, Darius; Miller, Albert; Kurtinaitis, Juozas; Valuckas, Konstantinas Povilas [Dept. of Radiotherapy, Inst. of Oncology, Vilnius Univ. (Lithuania); Haverkamp, Uwe [Dept. of Radiology, Clemenshospital, Muenster (Germany); Popov, Sergey [Dept. of Radiotherapy, Riga Eastern Hospital, Latvian Oncology Center, Riga (Latvia); Prott, Franz-Josef [Inst. of Radiology and Radiotherapy (RNS), St. Josefs Hospital, Wiesbaden (Germany)

    2009-11-15

    Purpose: to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). Patients and methods: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. Results: no acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% ({chi}{sup 2}-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). Conclusion: in this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term. (orig.)

  11. Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

    Directory of Open Access Journals (Sweden)

    Williams Scott

    2011-10-01

    Full Text Available Abstract Background Image-guided radiotherapy (IGRT increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically. Methods Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment. Results In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188. Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174. Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271. The median number of days with a toxicity was higher for ≥G2 (p = 0.0179 and ≥G3 frequency (p = 0.0027, ≥G2 diarrhoea (p = 0.0033 and ≥G2 fatigue (p = 0.0088 in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference. Conclusions In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment

  12. Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    . Radiation Toxins (SRD-1)had been isolated from Central Lymph of irradiated animals (cows, sheep, pigs). Experiments to study toxicity of Radiation Neurotoxins had been performed. Intravenous (IV) and intramuscular (IM) administration of RT SRD-1 to radiation naive animals had induced acute toxicity which referred to the harmful effects generated by high doses of radiation. In-jection of toxic doses of RT SRD-1 (Toxic doses: 0,1 mg/kg, 0,5mg/kg, 1 mg/kg, 10mg/kg,30 mg/kg, 50mg/kg,70 mg/kg,100 mg/kg, 110mg/kg)were compared to the similar effects caused by high doses of radiation. Results: Injection of SRD-1 ( Neurotoxin Cv ARS)of all ten tested toxic doses had caused a death of radiation naive animals within the first hours after admin-istration of toxins. For all animals in all experiments, a short period of extreme agitation was replaced by deep coma, and suppression of blood circulation and breathing. The results of postmortem section had showed characteristics of intra-cortical hemorrhage. Conclusions: Acute radiation injury induces a disorder of blood supply of the Central Nervous System (CNS). However, administration of SRD-1 Radiation Toxins to radiation naive animals produces crit-ically important inflammatory reactions with hemorrhagic stroke development. Neurotoxicity and Excitotoxicity are two stages of the pathological processes resulted in damaging and killing nerve cells thorough apoptotic necrosis. Excitotoxicity is well known as a pathological process that occurs when important excitatory neurotransmitters (glutamate, serotonin) over-activate the receptors -NMDA, AMPA, 5HT1, 5HT2, 5H3. Radiation Neurotoxins possibly act on the same receptors and activate the cell death mechanisms through direct or indirect excessive activation of same receptors.

  13. Acute Toxicity of Opuntia Ficus Indica and Pistacia Lentiscus Seed Oils in Mice

    OpenAIRE

    Boukeloua, A; Belkhiri, A; Djerrou, Z; Bahri, L; Boulebda, N; Pacha, Y Hamdi

    2012-01-01

    Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD50 values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opunti...

  14. Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

    International Nuclear Information System (INIS)

    Romanelli, Maria Fernanda

    2004-01-01

    Surfactants are synthetic organic compounds widely used in cosmetic, food, textile, dyers and paper production industries and in particular detergents and others cleaning products industries. The world consumption is nearly 8 million tons per year. One of the main environmental issues coming from the use of these compounds is their toxicity that compromises the biological treatment of effluents and the quality of receiving waters. The objective of this work was the application of ionizing radiation by electron beam in the degradation and reduction of acute and chronic toxicities of surfactants sodium dodecylsulfate (SDS), dodecyl p-benzenesulfonate acid (LAS) and sodium dodecyl p-benzenesulfonate (LAS). This treatment technology has been studied as a pre-treatment for effluents containing toxic and non-biodegradable compounds, before the biological treatment. Two acute toxicity assays were employed, one with the micro-crustacean Daphnia similis and the other with the luminescent bacterium Vibrio fischeri along with a chronic toxicity assay with the micro-crustacean Ceriodaphnia dubia (just for SDS and acid LAS) for the non-irradiated and irradiated samples and radiation doses 3.0 kGy, 6.0 kGy, 9.0 kGy and 12.0 kGy. Physical-chemical parameters were evaluated for the following up the degradation of the surfactant molecules. The reductions of acute toxicity varied between 72.49% and 90.98% for SDS, 18.22% and 78.98% for acid LAS and 82.66% and 94.26% for sodium LAS. For the chronic toxicity, the reduction percentages varied between 64.03% and 83.01% for SDS and 47.48% and 64.91% for acid LAS. When one considers the application of the electron beam as a pre-treatment of effluents containing high concentrations of surfactants, the toxicity is an essential parameter allowing the further biological treatment of these effluents. (author)

  15. Acute toxicity assessment of perfluorinated carboxylic acids towards the Baltic microalgae.

    Science.gov (United States)

    Latała, Adam; Nędzi, Marcin; Stepnowski, Piotr

    2009-09-01

    The presence of high-energy carbon-fluorine bonds in perfluoro compounds lends them great stability and causes them to be environmentally persistent. Relatively little is known about the acute toxicity of perfluorinated carboxylic acids (PFCAs) to ecotoxicological markers such as aquatic plants and animals. This study tested the toxicity of these compounds to the green alga Chlorella vulgaris, the diatom Skeletonema marinoi and the blue-green alga Geitlerinema amphibium, which are species representative of the algal flora of the Baltic Sea. The EC(50) values obtained range from 0.28 mM to 12.84 mM. A distinct relationship between hydrophobicity and toxicity is demonstrated. For every extra perfluoromethylene group in the alkyl chain, the toxicity increases twofold. LogEC(50) values are very well correlated linearly with both the number of carbon atoms in the perfluoroalkyl chain and the partition coefficients. The results also indicate that there are clear differences between the responses of particular taxonomic groups of algae: blue-green algae and diatoms are far more sensitive to PFCAs than green algae, probably because of differences in cell wall structure.

  16. Acute allergic reaction to oral quinine for malarial prevention: A case report

    Directory of Open Access Journals (Sweden)

    Sora Yasri

    2016-01-01

    Full Text Available Quinine is a classical antimalarial drug that is used worldwide. It is also used for pre-exposure of malaria before visiting to the jungle in the endemic area of malaria. In this article, the authors reported a case of acute allergic reaction to oral quinine for malarial prevention.

  17. Oral zinc supplementation for children with acute diarrhoea: a quasi-experimental study.

    Science.gov (United States)

    Dalfa, Rola Abu; El Aish, Khaled I Abu; El Raai, Mohamed; El Gazaly, Nermeen; Shatat, Ahmed

    2018-02-21

    Diarrhoea causes 15% of under-5 mortality in developing countries. Zinc (Zn) stores in the body are known to be depleted during acute diarrhoea. The aim of this study was to evaluate the efficacy of Zn given with standard treatment to children with acute or moderate diarrhoea. In this quasi-unmasked, parallel-group study, we enrolled children with diarrhoea at El-Dorra Paediatric Hospital, Gaza Strip, occupied Palestinian territory. Inclusion criteria were children with more than three unformed stools in the preceding 24 h, duration of diarrhoea up to 72 h, and ability to accept oral fluids or feeds. Recruited children were assigned equally to either oral rehydration salts (control group) or oral rehydration salts plus Zn sulphate (Zn group; 10 mg for children younger than 6 months; 20 mg for children aged 6 months and older). All treatments were taken orally for 14 days. Primary outcomes were duration and frequency of diarrhoea. Secondary outcomes included changes in bodyweight, drugs side-effects, and episodes of any or severe dehydration. Data were analysed with SPSS. Outcome measures were compared with the Mann-Whitney U-test, student's t test, odds ratio, or χ 2 test. The study was approved by the ministry of health and the Helsinki Committee in the Gaza Strip. Parents of the children provided verbally informed consent before participation. We enrolled 140 children (aged 1-120 months). Duration of diarrhoea in the Zn group was shorter than in the control group (2·34 days in the Zn group vs 7·20 days in the control group; pZinc supplementation added to standard treatment with oral rehydration salts was effective and resulted in good treatment of diarrhoea. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-01-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 ± 3mm (mean ± SD) and 10 ± 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 ± 13cGy with Hylaform vs. 106 ± 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  19. Ecotoxicological evaluation of leachate from the Limeira sanitary landfill with a view to identifying acute toxicity

    OpenAIRE

    José Euclides Stipp Paterniani; Ronaldo Teixeira Pelegrini; Núbia Natália de Brito Pelegrini

    2007-01-01

    Final disposal of solid waste is still a cause for serious impacts on the environment. In sanitary landfills, waste undergoes physical, chemical, and biological decomposition, generating biogas and leachate. Leachate is a highly toxic liquid with a very high pollution potential. The purpose of this work is to evaluate toxicity of in natura leachate samples collected from Limeira Sanitary Landfill, in Limeira, SP. The ecotoxicological evaluation comprised acute toxicity assays using as test or...

  20. High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolff, Hendrik Andreas; Bosch, Jan; Hennies, Steffen; Hess, Clemens F.; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Overbeck, Tobias [Dept. of Haematology and Oncology, Univ. Medicine Goettingen (Germany); Matthias, Christoph; Roedel, Ralph M. [Dept. of Otorhinolaryngology, Univ. Medicine Goettingen (Germany)

    2010-05-15

    Purpose: to test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and methods: from 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC {>=} 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis. Results: a statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC {>=} 3 acute organ toxicity had a 5-year overall survival rate of 4% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure. Conclusion: these data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials. (orig.)

  1. Analysis of acute and late toxicity of adjuvant radiotherapy in women with cervical and endometrial cancer

    International Nuclear Information System (INIS)

    Warenczak-Florczak, Z.; Roszak, A.; Wlodarczyk, H.; Wojciechowska-Lacka, A.

    2011-01-01

    Background: In case of pure prognostic factors women with cervical and endometrial cancer after surgical operation need to be treated with radiotherapy . Every radiation treatment may be involved with toxicity, acute and late. Material and methods: Performed was detailed analysis of 173 patients with cervical (38) and endometrial (135) cancer. We evaluated early and late post radiation reactions in all patients. Results: Acute reactions were found in 48.5% and late toxicity was found in 9.8% of patients. Women with endometrial cancer were significantly older then patients with cervical cancer (p < 0.002). Higher percentage of acute and late toxicity was observed from the bowel tah urinary tract (26% and 22.5% - acute; 8.1% and 1.73% - late). Higher percentage of acute side effects was observed in patients with cervical than with endometrial cancer (60.5% and 33.7%). Late post radiation reaction predominate also in patient with cervical cancer (13.2% and 8.9%). The adverse effects were associated with prolonged time of treatment due to breaks in radiotherapy. Higher percentage of breaks was found in older patients, more frequent in patient with endometrial than in cervical cancer group (7.4% and 2.6%).To conclude early postradiation reaction appeared more frequently, than late post radiation reactions. It was stated that early and late post radiation reaction appear more frequently in women with cervical than in endometrial cancer. Interruption in radiation delivery was longer than seven days in group with endometrial cancer that leads to extension of complete radiation treatment. (authors)

  2. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  3. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    Energy Technology Data Exchange (ETDEWEB)

    McFarland, Craig A., E-mail: craig.a.mcfarland@us.army.mi [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Quinn, Michael J [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Boyce, John [Biotechnics, LLC, Hillsborough, NC 27278 (United States); LaFiandra, Emily M; Bazar, Matthew A [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States); Johnson, Mark S [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States)

    2011-02-15

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD{sub 50} values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at {>=}15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: Oral LD{sub 50} (mg/kg) values were 1406 for male and 1867 for female lizards. Dose-dependent hepatocellular transdifferentiation was observed at {>=}5 mg/kg-d. Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  4. Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

    International Nuclear Information System (INIS)

    McFarland, Craig A.; Quinn, Michael J.; Boyce, John; LaFiandra, Emily M.; Bazar, Matthew A.; Talent, Larry G.; Johnson, Mark S.

    2011-01-01

    The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD 50 values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: → Oral LD 50 (mg/kg) values were 1406 for male and 1867 for female lizards. → Dose-dependent hepatocellular transdifferentiation was observed at ≥5 mg/kg-d. → Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. → Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

  5. Acute Lidocaine Toxicity: a Case Series

    Directory of Open Access Journals (Sweden)

    Mitra Rahimi

    2018-06-01

    Full Text Available Introduction: Parenteral form of lidocaine is the best-known source of lidocaine poisoning. This study aimed to evaluate the characteristics of acute lidocaine toxicity.Methods: In this retrospective cross-sectional study, demographics, clinical presentation, laboratory findings, and outcome of patients intoxicated with lidocaine (based on  ICD10 codes admitted to Loghman Hakim Hospital, during April 2007 to March 2014 were analyzed.Results: 30 cases with the mean age of 21.83 ± 6.57 year were studied (60% male. All subjects had used either 6.5% lidocaine spray or 2% topical formulations of lidocaine. The mean consumed dose of lidocaine was 465 ± 318.17 milligrams. The most frequent clinical presentations were nausea and vomiting (50%, seizure (33.3%, and loss of consciousness (16.7%. 22 (73.3% cases had normal sinus rhythm, 4 (13.3% bradycardia, 2 (6.7% ventricular tachycardia, and 2 (6.7% had left axis deviation. 11 (36.6% cases were intubated and admitted to intensive care unit (ICU for 6.91 ± 7.16 days. Three patients experienced status epilepticus that led to cardiac arrest, and death (all cases with suicidal intention.Conclusion: Based on the results of this study, most cases of topical lidocaine toxicity were among < 40-year-old patients with a male to female ratio of 1.2, with suicidal attempt in 90%, need for intensive care in 36.6%, and  mortality rate of 10%.

  6. The acute toxicity of the metaldehyde on the climbing perch

    Science.gov (United States)

    Wahida Mohamad Ismail, Syamimi; Aini Dahalan, Farrah; Zakaria, Ammar; Mad Shakaff, Ali Yeon; Aqlima Ahmad, Siti; Shukor, Mohd Yunus Abd; Khalizan Sabullah, Mohd; Khalil, Khalilah Abdul; Jalil, Mohd Faizal Ab

    2018-03-01

    In Asia, Climbing perch (Anabas testudineus) is commonly found in paddy fields and irrigation systems. Due to its habitat, Climbing perch is exposed to toxic pesticides used in paddy fields such as metaldehyde which is one of the most widely used molluscicide. This study aims to determine the acute toxicity Lethal Concentration50 (LC50) of metaldehyde and its effect on the behaviour and physical changes of the Climbing perch. The fish mortality responses to six different metaldehyde concentrations ranging from 180 to 330 mg/L were investigated. The 96-h LC50 values were determined and analysed using three different analysis methods which is arithmetic, logarithmic and probit graphic. The LC50 values obtained in this study were 239, 234 and 232 mg/L, respectively. After 96-h of exposure to metaldehyde, the fish showed a series of abnormal behavioural response in all cases: imbalance position, and restlessness of movement. The LC50 values show that metaldehyde is moderately toxic to the Climbing perch indicating that metaldehyde is not destructive to Climbing perch. However, long term exposure of aquatic organisms to the metaldehyde means a continuous health risk for the fish population as they are more vulnerable and it is on high risk for human to consume this toxicated fishes.

  7. Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

    Science.gov (United States)

    Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

    2014-07-01

    Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

  8. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  9. Antimicrobial activity and toxicity in vitro and in vivo of Equisetum hyemale extracts

    Directory of Open Access Journals (Sweden)

    Geisiany Maria de Queiroz

    2014-09-01

    Full Text Available Equisetum hyemale L, (Equisetaceae species is considered a medicinal plant used in the form of teas to combat infectious or inflammation diseases, presenting several compounds related to these actions, There are no extensive studies about the use against different microbial groups as well as for the toxicity, The objective of these studies was for the first time evaluated the antimicrobial activity against oral microorganisms and the in vitro and in vivo toxicity of 70% ethanol and methanol E, hyemale extracts, Antimicrobial activity assays were performed by broth microdilution technique to determine the Minimum Inhibitory Concentration (MIC and the cytoxicity was assayed in vitro and acute toxicity in vivo was performed with mice, The methanol extracts, showed better antimicrobial activity against oral microorganisms whit MIC of 0.5 mg/mL, Both extracts presented low cytotoxicity even in high concentrations and the 70% ethanol extract of E, hyemale did not present toxicity inducing significant alterations and/or death in mice, This results suggests that both extracts exhibits great potential to therapeutic applications.

  10. Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

    Directory of Open Access Journals (Sweden)

    Letícia Flohr

    2012-01-01

    Full Text Available Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3 induced the highest toxicity level to Daphnia magna(CE50,48 h=2.21%. A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min=12.08%. All samples of pulp and paper wastes, and a textile waste (sample TX2 induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

  11. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    International Nuclear Information System (INIS)

    Lips, Irene M; Dehnad, Homan; Gils, Carla H van; Boeken Kruger, Arto E; Heide, Uulke A van der; Vulpen, Marco van

    2008-01-01

    We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

  12. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    Directory of Open Access Journals (Sweden)

    Boeken Kruger Arto E

    2008-05-01

    Full Text Available Abstract We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment and weekly during treatment (acute toxicity were scored using the Common Toxicity Criteria (CTC. The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU complaints and 2% experienced grade 2 gastrointestinal (GI complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4. In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

  13. Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

    Directory of Open Access Journals (Sweden)

    Maznah Ismail

    2013-06-01

    Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  14. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

    International Nuclear Information System (INIS)

    Haj Mohammad, Nadia; Hulshof, Maarten CCM; Bergman, Jacques JGHM; Geijsen, Debby; Wilmink, Johanna W; Berge Henegouwen, Mark I van; Laarhoven, Hanneke WM van

    2014-01-01

    Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group

  15. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Haj Mohammad, Nadia [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hulshof, Maarten CCM [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Bergman, Jacques JGHM [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Geijsen, Debby [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Wilmink, Johanna W [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Berge Henegouwen, Mark I van [Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Laarhoven, Hanneke WM van [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-01-31

    Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

  16. Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

    Science.gov (United States)

    Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

    2008-05-01

    Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

  17. Acute silver toxicity in aquatic animals is a function of sodium uptake rate

    DEFF Research Database (Denmark)

    Bianchini, A.; Grosell, Martin Hautopp; Gregory, S.

    2002-01-01

    -specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from...... toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarus diogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above...... hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity...

  18. The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity

    International Nuclear Information System (INIS)

    Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean Marc; Lefloch, Olivier; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdin, Sylvain; Bachaud, Jean Marc; Maingon, Philippe; Lagrange, Jean-L.eon; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal M.D.; Hay, Men H.; Dubray, Bernard; Luporsi, Elisabeth; Bey, Pierre

    2004-01-01

    Purpose: To describe treatments and acute tolerance in a randomized trial comparing 70 Gy and 80 Gy to the prostate in patients with localized prostate cancer. Methods and materials: Between September 1999 and February 2002, 306 patients were randomized to receive 70 Gy (153 patients) or 80 Gy (153 patients) in 17 institutions. Patients exhibited intermediate-prognosis tumors. If the risk of node involvement was greater than 10%, surgical staging was required. Previous prostatectomy was excluded, and androgen deprivation was not admitted. The treatment was delivered in two steps. PTV1-including seminal vesicles, prostate, and a 1-0.5-cm margin-received 46 Gy given with a 4-field conformal technique. PTV2, reduced to prostate with the same margins, irradiated with at least 5 fields. Dose was prescribed according to ICRU recommendations in the 70 Gy group, but adapted at the 80 Gy level. Results: All patients but one in the 80 Gy arm completed the treatment. In the 70 Gy arm, the mean dose to the PTV2 was 69.5 Gy. In the 80 Gy arm, the mean dose in the PTV2 was 78.5 Gy. Acute toxicity according to Radiation Therapy Oncology Group scale during treatment was reported in 306 patients. There was no statistically significant difference between the two arms: 12% had no toxicity, 80% complained of bladder toxicity, and 70% complained of rectal symptoms. Two months after the end of treatment, 43% of the 70 Gy level and 48% of the 80 Gy level complained of side effects, including 24% and 20% of sexual disorders. There was 6% and 2% of Grade 3 urinary and rectal toxicity. Five patients required a 10-29-day suspension of the treatment. Acute Grade 2 and 3 side effects were related to PTV and CTV1 size, which was the only independent predictive factor in multivariate analysis. Toxicity was not related to the center, age, arm of treatment, or selected data from dose-volume histogram of organ at risk. Conclusion: Treatments were completed in respect to constraints. Acute toxicity

  19. Comparison of toxicity of acute overdoses with citalopram and escitalopram.

    Science.gov (United States)

    Hayes, Bryan D; Klein-Schwartz, Wendy; Clark, Richard F; Muller, Allison A; Miloradovich, Jane E

    2010-07-01

    Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002-2005. There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68-70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p escitalopram (p = 0.011). In children escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial

    International Nuclear Information System (INIS)

    Pollack, Alan; Hanlon, Alexandra L.; Horwitz, Eric M.; Feigenberg, Steven J.; Konski, Andre A.; Movsas, Benjamin; Greenberg, Richard E.; Uzzo, Robert G.; Ma, C.-M. Charlie; McNeeley, Shawn W.; Buyyounouski, Mark K.; Price, Robert A.

    2006-01-01

    Purpose: The α/β ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. Patients and Methods: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. Results: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. Conclusion: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described

  1. Acute toxicity of birch tar oil on aquatic organisms

    Directory of Open Access Journals (Sweden)

    M. HAGNER

    2008-12-01

    Full Text Available Birch tar oil (BTO is a by-product of processing birch wood in a pyrolysis system. Accumulating evidence suggests the suitability of BTO as a biocide or repellent in terrestrial environments for the control of weeds, insects, molluscs and rodents. Once applied as biocide, BTO may end up, either through run-off or leaching, in aquatic systems and may have adverse effects on non-target organisms. As very little is known about the toxicity of BTO to aquatic organisms, the present study investigated acute toxicity (LC50/EC50 of BTO for eight aquatic organisms. Bioassays with the Asellus aquaticus (crustacean, Lumbriculus variegatus (oligochaeta worm, Daphnia magna (crustacean, Lymnea sp. (mollusc, Lemna minor (vascular plant, Danio rerio (fish, Scenedesmus gracilis (algae, and Vibrio fischeri (bacterium were performed according to ISO, OECD or USEPA-guidelines. The results indicated that BTO was practically nontoxic to most aquatic organisms as the median effective BTO concentrations against most organisms were >150 mg L-1. In conclusion, our toxicity tests showed that aquatic organisms are to some extent, invariably sensitive to birch tar oil, but suggest that BTO does not pose a severe hazard to aquatic biota. We deduce that, unless BTOs are not applied in the immediate vicinity of water bodies, no special precaution is required.;

  2. Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Paumen, M.L.; Dmytrasz, B.

    2011-12-15

    This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

  3. Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

    International Nuclear Information System (INIS)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Paumen, M.L.; Dmytrasz, B.

    2011-12-01

    This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

  4. Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat

    Energy Technology Data Exchange (ETDEWEB)

    Fan, F. (Dept. of Pharmacology, Toxicology and Therapeutics, Univ. of Kansas Medical Center, Kansas City, KS (United States)); Rozman, K.K. (Section of Environmental Toxicology, GSF-Inst. fuer Toxikologie, Neuherberg (Germany))

    1994-12-01

    The aim of this study was to examine the acute toxicity of TCDD in a rat strain other than the Sprague-Dawley (S-D) rat. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 [mu]g/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T[sub 4] (TT[sub 4]) and total T[sub 3] (TT[sub 3]) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), [gamma]-glutamyl transpeptidase ([gamma]-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic [gamma]-GT activity was also dose-dependently reduced. However, unlike in S-D rats, these dose-responses occurred in a higher dose range than the reduction of PEPCK activity which appears to be the explanation for the decreased susceptibility of L-E rats to TCDD. Serum TT[sub 4] levels were significantly decreased at all doses, whereas the serum concentration of TT[sub 3] appeared unaffected. The results of this study suggest that subtle differences in the regulation of intermediary metabolism between these two strains of rats are responsible for strain differences in the susceptibility to TCDD. (orig.)

  5. Temporomandibular joint dislocation due to acute propranolol intoxication

    Directory of Open Access Journals (Sweden)

    Abbas Aghabiklooei

    2010-07-01

    Full Text Available Abbas Aghabiklooei1, Homan Elahi2, Babak Mostafazadeh31Department of Medical Toxicology and Forensic Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Firouzgar Hospital, Department of ENT, Tehran, Iran; 3Department of Medical Toxicology and Forensic Medicine, Shaheed Beheshty University of Medical Sciences, Tehran, IranAbstract: Temporomandibular joint (TMJ dislocation has not previously been reported as a complication of beta-blocker toxicity. We are reporting two cases of TMJ dislocation resulted from acute severe intoxication with pure propranolol (PPL for the first time. Bilateral TMJ dislocation happened in two patients who were admitted to intensive care unit with diagnosis of severe acute PPL toxicity. Clinical diagnosis of TMJ dislocation was obtained by physical examination. Successful reduction was performed for both patients without subsequent recurrence in two weeks following hospital discharge. Both of our subjects had no previous history of lower jaw dislocation. There was not any risk factor for dislocation such as convulsion during admission period, recent face trauma, or oral manipulation by the medical team. This study showed that TMJ dislocation may occur after severe acute PPL toxicity probably due to spastic contraction of the lateral pterygoid muscle. This is against previously mentioned hypothesis that stated masseteric muscles contraction as the main cause of a bilateral dislocated TMJ.Keywords: propranolol, toxicity, temporomandibular joint dislocation

  6. Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

    Science.gov (United States)

    Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

    2017-06-01

    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The Acute Toxicity Test of Methanolic Extract of Hyptis pectinata Poit on Liver Balb/c Mice

    Science.gov (United States)

    Suzery, M.; Cahyono, B.; Astuti, P.

    2017-02-01

    Plants from Lamiaceae family has almost entirely reported having physiological activities. One of them is Hyptis pectinata Poit plant. Research on the toxicity of Hyptis pectinata needs to be done to protect people from the possibility of its harmful effects. This study aim to know the acute toxicity effects of Hyptis pectinata extract (HPE) on liver of Balb/c mice. This research was a laboratory experimental study using the post test only controlled group design. Balb/c mice were randomly divided into 4 groups. K (control group), P1, P2 and P3 (treatment groups; given HPE 200mg/kgBW, 1000 mg/kgBW, and 5000 mg/kgBW, respectively). The extract was orally given with gastric tube on the first day and the mice were terminated at the 8th day then the livers were observed. The Kruskal-Wallis test for macroscopic morphological and volume of the liver showed there were no significant difference with p=0.406 and p=0.054. The highest liver histopathological score was in P3 group. The Kruskal-Wallis test showed significantly difference (p=0.000). Continued with Mann-Withney test that showed a significant difference in K-P1 (p=0.009), K-P2 (p=0.009), K-P3 (p=0.009), P1-P2 (p=0.028), and P1-P3 (p=0.009). In conclusion, the HPE is safe to use which has no complication with liver of mice.

  8. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Ying-Mei Niu

    2016-01-01

    Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

  9. The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Baglan, Kathy L.; Frazier, Robert C.; Yan Di; Huang, Raywin R.; Martinez, Alvaro A.; Robertson, John M.

    2002-01-01

    Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V 15 ) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy

  10. Comparative Analysis of the Solid Phases of Bronchoalveolar Lavage and Oral Fluid in Children with Acute Necrotizing Pneumonia

    Directory of Open Access Journals (Sweden)

    V.N. Grona

    2014-05-01

    Full Text Available The growing number of acute lung abscesses, and pleural empyema, high invalidization and mortality determine the necessity for search of new methods of its diagnosis and treatment. The aim of this research was to study the morphological characteristics of in bronchoalveolar lavage and oral fluid facies in children with acute destructive pneumonias and to find out correlations between them. We examined 24 patients of department of purulent surgery in age from 1 to 14 years. Collection of mixed unstimulated oral fluid was carried out by spitting into special tubes, bronchoalveolar lavage was obtained by bronchoscopy. There has been revealed a correlation between morphological pattern of bronchoalveolar lavage and oral fluid in children depending on the pathological condition of the body.

  11. The effect of aerobic exercise on treatment-related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer.

    Science.gov (United States)

    Kapur, G; Windsor, P M; McCowan, C

    2010-09-01

    We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference in bladder toxicity scores between the two groups (P=0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.

  12. Evaluation of acute toxicity of babassu mesocarp in mice

    Directory of Open Access Journals (Sweden)

    Elizabeth S. B. Barroqueiro

    2011-07-01

    Full Text Available The safety of babassu mesocarp (Orbignya phalerata Mart., Arecaceae, which exhibited anti-inflammatory and antithrombotic activities, was evaluated by determining the potential acute toxicity in mice. A lyophilized ethanol extract of babassu mesocarp (BME was administered to C3H/HePas mice (10/group in a single dose of 1000, 3000 and 5000 mg/kg, by gavage. General behavior adverse effects and mortality were determined for up to fourteen days. Selected biochemical parameters including glucose, triacylglyceride, cholesterol, urea, alkaline phosphatase and creatinine were determined by colorimetric assay. The heart, liver, spleen, kidneys and brain were weighted and evaluated macro and microscopically. The median lethal dose (LD50 of BME was greater than 5000 mg/kg. No behavior or body weight alterations were detected after the treatment. The acute treatment with BME has no effect on macroscopic and microscopic aspect of examined organs. Instead, BME increased the alkaline phosphatase and reduced the urea concentration in all groups. A significant increase on triacylglyceride was detected in the group BME1000. In conclusion, the acute treatment with high doses of BME can affect some biochemical parameters with a long lasting effect, although any change was detected at tissue level or body and organ weight.

  13. Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

    Science.gov (United States)

    Sadekar, S; Ghandehari, H

    2012-05-01

    This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Microbial transformation from normal oral microbiota to acute endodontic infections

    Directory of Open Access Journals (Sweden)

    Hsiao William WL

    2012-07-01

    Full Text Available Abstract Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections. Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals.

  15. Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

    Science.gov (United States)

    Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

    2003-05-01

    The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC

  16. Is the OECD acute worm toxicity test environmentally relevant? The effect of mineral form on calculated lead toxicity

    International Nuclear Information System (INIS)

    Davies, N.A.Nicola A.; Hodson, M.E.Mark E.; Black, S.Stuart

    2003-01-01

    The current OECD acute worm toxicity test does not relate well to ambient conditions. - In a series of experiments the toxicity of lead to worms in soil was determined following the draft OECD earthworm reproduction toxicity protocol except that lead was added as solid lead nitrate, carbonate and sulphide rather than as lead nitrate solution as would normally be the case. The compounds were added to the test soil to give lead concentrations of 625-12500 μg Pb g -1 of soil. Calculated toxicities of the lead decreased in the order nitrate>carbonate>sulphide, the same order as the decrease in the solubility of the metal compounds used. The 7-day LC 50 (lethal concentration when 50% of the population is killed) for the nitrate was 5321±275 μg Pb g -1 of soil and this did not change with time. The LC 50 values for carbonate and sulphide could not be determined at the concentration ranges used. The only parameter sensitive enough to distinguish the toxicities of the three compounds was cocoon (egg) production. The EC 50 s for cocoon production (the concentration to produce a 50% reduction in cocoon production) were 993, 8604 and 10246 μg Pb g -1 of soil for lead nitrate, carbonate and sulphide, respectively. Standard toxicity tests need to take into account the form in which the contaminant is present in the soil to be of environmental relevance

  17. Development of thresholds of excess toxicity for environmental species and their application to identification of modes of acute toxic action.

    Science.gov (United States)

    Li, Jin J; Zhang, Xu J; Yang, Yi; Huang, Tao; Li, Chao; Su, Limin; Zhao, Yuan H; Cronin, Mark T D

    2018-03-01

    The acute toxicity of organic pollutants to fish, Daphnia magna, Tetrahymena pyriformis, and Vibrio fischeri was investigated. The results indicated that the Toxicity Ratio (TR) threshold of log TR =1, which has been based on the distribution of toxicity data to fish, can also be used to discriminate reactive or specifically acting compounds from baseline narcotics for Daphnia magna and Vibrio fischeri. A log TR=0.84 is proposed for Tetrahymena pyriformis following investigation of the relationships between the species sensitivity and the absolute averaged residuals (AAR) between the predicted baseline toxicity and the experimental toxicity. Less inert compounds exhibit relatively higher toxicity to the lower species (Tetrahymena pyriformis and Vibrio fischeri) than the higher species (fish and Daphnia magna). A greater number of less inert compounds with log TR greater than the thresholds was observed for Tetrahymena pyriformis and Vibrio fischeri. This may be attributed to the hydrophilic compounds which may pass more easily through cell membranes than the skin or exoskeleton of organisms and have higher bioconcentration factors in the lower species, leading to higher toxicity. Most of classes of chemical associated with excess toxicity to one species also exhibited excess toxicity to other species, however, a few classes with excess toxicity to one species exhibiting narcotic toxicity to other species and thus may have different MOAs between species. Some ionizable compounds have log TR much lower than one because of the over-estimated log K OW . The factors that influence the toxicity ratio calculated from baseline level are discussed in this paper. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Acute toxicity of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives

    Directory of Open Access Journals (Sweden)

    D. M. Danilchenko

    2017-09-01

    Full Text Available The purpose of our work was the further exploration of the new 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-1,2,4-triazole-3-thiol alkyl derivatives’ acute toxicity, setting some patterns of alkyl substituents influence by the Sulfur atom on the acute toxicity. Research materials and methods. In this study we used first time synthesized 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole-3-thione derivatives. Acute toxicity was conducted on white rats weighing 160–250 g, which were injected once intraperitoneally with the investigated substances. The rats were received from the nursery of the Pharmacology and Toxicology Institute of Ukraine Medical Sciences Academy. The animals were kept on a standard diet with natural light mode "day-night". Results and their discussion. After the acute toxicity studies in a group of 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkyl derivatives it was found that among all studied structures the most toxic was 2e, LD50 of which was 263 mg/kg, and the least toxic compound was 2a, LD50 of which was 1570 mg/kg, that belongs to the V toxicity class. After comparing the acute toxicity of well-known antimycotic agent fluconazole with the studied compounds it can be argued that most compounds are less toxic than the comparison drug fluconazole with the index of LD50 ˃320 mg/kg. It was found that the transition in a group from butyl to decyl, octyl, ventyl, propyl, nonyl and heptyl substituents in the molecule of 3-alkylthio 5-(furan-2-yl-4-amino-4H-1,2,4-triazole is accompanied by the toxicity increasing. Speaking about the 5-(2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole 3-alkylthio derivatives we can find that this dependence is observed in a number from propyl, pentyl, nonil, butyl, heksyl, octyl and heptyl hydrocarbon chains. Conclusions. The investigated 3-alkylthio 5-(furan-2-yl, 2-metylfuran-3-yl-4-amino-4H-1,2,4-triazole derivatives belong to the IV-V toxicity class. The toxicity of 5

  19. Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences

    NARCIS (Netherlands)

    Brink, Van den P.J.; Smeden, Van J.M.; Bekele, R.S.; Dierick, Wiebe; Gelder, De Daphne M.; Noteboom, Maarten; Roessink, Ivo

    2016-01-01

    Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to

  20. Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Arcangeli, Giorgio; Fowler, Jack; Gomellini, Sara; Arcangeli, Stefano; Saracino, Biancamaria; Petrongari, Maria Grazia; Benassi, Marcello; Strigari, Lidia

    2011-01-01

    Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

  1. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    International Nuclear Information System (INIS)

    Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-01-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

  2. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    Science.gov (United States)

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  3. Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

    International Nuclear Information System (INIS)

    Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2010-01-01

    Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R 2 , 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

  4. The Acute Toxicity of Major Ion Salts to Ceriodaphnia dubia: I. Influence of background water chemistry.

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset provides concentration-response data and associated general chemistry conditions for 26 experiments consisting of 149 tests regarding the acute toxicity...

  5. The Acute Toxicity of Major Ions to Ceriodaphnia dubia. II. Empirical Relationships in Binary Salt Mixtures

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset provides concentration-response data and associated general chemistry conditions for 29 experiments consisting of 209 tests regarding the acute toxicity...

  6. In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves.

    Science.gov (United States)

    Fonseca, Aldilane Gonçalves; Ribeiro Dantas, Luzia Leiros Sena Fernandes; Fernandes, Júlia Morais; Zucolotto, Silvana Maria; Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira; Rocha, Hugo Alexandre Oliveira; Lemos, Telma Maria Araújo Moura

    2018-01-01

    The species Kalanchoe brasiliensis , known as "Saião , " has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis . The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo , the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

  7. Acute toxicity of chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Roedel, C.; Fietkau, R.; Keilholz, L.; Grabenbauer, G.G.; Kessler, H.; Martus, P.; Sauer, R.

    1997-01-01

    Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) ± 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m 2 /d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [de

  8. A proposal of classification for acute toxicity; Una scala di tossicita`

    Energy Technology Data Exchange (ETDEWEB)

    Oddo, N. [Ecotox srl, Pregnana Milanese (Italy)

    1998-05-01

    A classification for acute toxicity is proposed, including the effects to low level exposures (Hormesis). The criteria, the measurement units and the correlations to chronic and to genotoxicity of the proposed classification are discussed. [Italiano] Viene proposta una scala per la tossicita` acuta, comprendendovi gli effetti deboli (Ormesi). Vengono discussi i criteri di formulazione della scala, le unita` di misura adottate, e le relazioni con la tossicita` cronica e con la genotossicita`.

  9. Acute and additive toxicity of ten photosystem-II herbicides to seagrass

    OpenAIRE

    Adam D. Wilkinson; Catherine J. Collier; Florita Flores; Andrew P. Negri

    2015-01-01

    Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ...

  10. In vitro antioxidant potential of medicinal plant extracts and their activities against oral bacteria based on Brazilian folk medicine.

    Science.gov (United States)

    Alviano, Wagner S; Alviano, Daniela S; Diniz, Cláudio G; Antoniolli, Angelo R; Alviano, Celuta S; Farias, Luiz M; Carvalho, Maria Auxiliadora R; Souza, Margareth M G; Bolognese, Ana Maria

    2008-06-01

    This study aims to determine antibacterial activities of Cocos nucifera (husk fiber), Ziziphus joazeiro (inner bark), Caesalpinia pyramidalis (leaves), aqueous extracts and Aristolochia cymbifera (rhizomes) alcoholic extract against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans and Lactobacillus casei. The antioxidant activity and acute toxicity of these extracts were also evaluated. The plant extracts antibacterial activity was evaluated in vitro and the minimal inhibitory concentration (MIC) was determined by the broth micro-dilution assay. The bacterial killing kinetic was also evaluated for all extracts. In addition, the antibacterial effect of the extracts was tested in vitro on artificial oral biofilms. The acute toxicity of each extract was determined in according to Lorke [Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983;54:275-87] and the antioxidant activity was evaluated by DPPH photometric assay [Mensor LL, Menezes FS, Leitão GG, Reis AS, Santos TC, Coube CS, et al. Screening of Brazilian plants extract for antioxidant activity by the use of DPPH free radical method. Phytother Res 2001;15:127-30]. MIC and the bactericidal concentrations were identical, for each evaluated extract. However, microbes of artificial biofilms were less sensitive to the extracts than the planktonic strains. A. cymbifera extract induced the highest bactericidal effect against all tested bacteria, followed by C. nucifera, Z. joazeiro and C. pyramidalis extracts, respectively. All extracts showed good antioxidant potential, being C. nucifera and C. pyramidalis aqueous extracts the most active ones. In conclusion, all oral bacteria tested (planktonic or in artificial biofilms) were more susceptible to, and rapidly killed in presence of A. cymbifera, C. pyramidalis and C. nucifera than Z. joazeiro extracts, respectively. Thus, these extracts may be of great interest for future studies about treatment of

  11. Hepatoprotective Effect of Metadoxine on Acetaminophen-induced Liver Toxicity in Mice

    Directory of Open Access Journals (Sweden)

    Parvin Mazraati

    2018-01-01

    Full Text Available Background: Metadoxine (pyridoxine pyrrolidone carboxylate is considered to be a beneficial agent for the treatment of experimental hepatotoxicity due to alcohol, CCl4, and bile duct ligation. Hence, the therapeutic effect of metadoxine and N-acetylcysteine (NAC as reference drug was investigated in mice exposed to acute hepatotoxicity induced by a single oral toxic dose of acetaminophen (650 mg/kg. Materials and Methods: Metadoxine (200 and 400 mg/kg and NAC (300 mg/kg were given orally (p. o., 2 h after acetaminophen administration. Serum aminotransferases, aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, total bilirubin, hepatic glutathione (GSH, and malondialdehyde (MDA levels were determined for evaluating the extent of hepatotoxicity due to acetaminophen and its protection by metadoxine. Results: Findings indicated that metadoxine significantly reduced the level of serum ALT, AST, and ALP but not total bilirubin which increased by acetaminophen intoxication. Administration of metadoxine also attenuated oxidative stress by suppressing lipid peroxidation (MDA and prevented the depletion of reduced GSH level which caused by acetaminophen toxicity. Besides, metadoxine ameliorated histopathological hepatic tissue injury induced by acetaminophen. Conclusion: In most parameters examined, the effect of metadoxine was comparable to NAC. Hence, metadoxine could be considered as a beneficial therapeutic candidate to protect against acute acetaminophen hepatotoxicity.

  12. Acute and chronic toxicity of effluent water from an abandoned uranium mine.

    Science.gov (United States)

    Antunes, S C; Pereira, R; Gonçalves, F

    2007-08-01

    Inactive or abandoned mines represent a significant source of environmental, chemical, physical, and aesthetic impact. Among concerning situations, the occurrence of abandoned or semi-abandoned mine-associated ponds (for sedimentation of solids, for effluent neutralization, or for washing the ore) is a common feature in this type of system. These ponds are a source of contamination for the groundwater resources and adjacent soils, because they lack appropriate impermeabilization. The use of this water for agriculture may also pose chronic risks to humans. In Portugal, these problems have been diagnosed and some remediation projects have been developed. The purpose of our study was to evaluate the acute and chronic toxicity of water samples collected from the aquatic system surrounding an abandoned uranium mine (Cunha Baixa, Mangualde, Central Portugal). The present study focuses on the water compartment, whose toxicity was evaluated by means of standard toxicity assays using two Daphnia species (D. longispina and D. magna). Three different ponds were used in the characterization of the aquatic system from Cunha Baixa mine: a reference pond (Ref), a mine effluent treatment pond (T), and a mine pit pond (M). Metal analyses performed in the water samples from these ponds showed values that, in some cases, were much higher than maximum recommendable values established (especially Al, Mn) by Portuguese legislation for waters for crop irrigation. Acute toxicity was only observed in the mine pit pond, with EC(50) values of 28.4% and 50.4% for D. longispina and D. magna, respectively. The significant impairment of chronic endpoints, translated in reductions in the population growth rate for both species, gives rise to concerns regarding the potential risks for aquatic zooplanktonic communities, from local receiving waters, potentially exposed to point source discharges of the treated and nontreated effluent from Cunha Baixa uranium mine.

  13. Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests

    Directory of Open Access Journals (Sweden)

    Débora Rebechi

    2014-09-01

    Full Text Available Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests. Organophosphate compounds are used in agro-systems, and in programs to control pathogen vectors. Because they are continuously applied, organophosphates often reach water sources and may have an impact on aquatic life. The effects of acute and chronic exposure to the organophosphate insecticide malathion on the midge Chironomus sancticaroli are evaluated. To that end, three biochemical biomarkers, acetylcholinesterase (AChE, alpha (EST-α and beta (EST-β esterase were used. Acute bioassays with five concentrations of malathion, and chronic bioassays with two concentrations of malathion were carried out. In the acute exposure test, AChE, EST-α and EST-β activities declined by 66, 40 and 37%, respectively, at 0.251 µg L-1 and more than 80% at 1.37, 1.96 and 2.51 µg L-1. In chronic exposure tests, AChE and EST-α activities declined by 28 and 15% at 0.251 µg L-1. Results of the present study show that low concentrations of malathion can influence larval metabolism, indicating high toxicity for Chironomus sancticaroli and environmental risk associated with the use of organophosphates.

  14. Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer

    International Nuclear Information System (INIS)

    Broek, Guido B. van den; Balm, Alfons J.M.; Brekel, Michiel W.M. van den; Hauptmann, Michael; Schornagel, Jan H.; Rasch, Coen R.N.

    2006-01-01

    Background and purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. Patients and methods: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. Results: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). Conclusions: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively

  15. Stereotactic radiotherapy of meningiomas. Symptomatology, acute and late toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R. [Dept. of Radiation Oncology, Univ. of Gisssen (Germany); Dept. of Radiation Oncology, Marburg Univ. (Germany); Hamm, K.; Surber, G.; Kleinert, G. [Dept. of Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

    2006-07-15

    Background and purpose: stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. Patients and methods: between 1997-2003, 224 patients were treated with SRT (n= 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. Results: the median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III ) was rarely seen (2.5%). Clinically significant late morbidity (III -IV ) or new cranial nerve palsies did not occur. Conclusion: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended. (orig.)

  16. Acute toxicity of heavy metals towards freshwater ciliated protists

    International Nuclear Information System (INIS)

    Madoni, Paolo; Romeo, Maria Giuseppa

    2006-01-01

    The acute toxicity of five heavy metals to four species of freshwater ciliates (Colpidium colpoda, Dexiotricha granulosa, Euplotes aediculatus, and Halteria grandinella) was examined in laboratory tests. After exposing the ciliates to soluble compound of cadmium, copper, chromium, lead, and nickel at several selected concentrations, the mortality rate was registered and the LC 5 values (with 95% confidence intervals) were calculated. Large differences appeared in sensitivities of the four species to the metals. H. grandinella showed the highest sensitivity for cadmium (0.07 mg l -1 , LC 5 ) and lead (0.12 mg l -1 , LC 5 ), whilst E. aediculatus showed the highest sensitivity for nickel (0.03 mg l -1 , LC 5 ). The comparison with data obtained with other species indicate that Halteria grandinella and Euplotes aediculatus are excellent and convenient bioindicator for evaluating the toxicity of waters and wastewaters polluted by heavy metals. The short time (24 h) and simplicity of the test procedure enable this test to be used in laboratory studies. - Ciliated protozoa are suitable bioindicators of heavy metal pollution in freshwater environments

  17. Dose-Volume Relationships for Acute Bowel Toxicity in Patients Treated With Pelvic Nodal Irradiation for Prostate Cancer

    International Nuclear Information System (INIS)

    Fiorino, Claudio; Alongi, Filippo; Perna, Lucia; Broggi, Sara; Cattaneo, Giovanni Mauro; Cozzarini, Cesare; Di Muzio, Nadia; Fazio, Ferruccio; Calandrino, Riccardo

    2009-01-01

    Purpose: To find correlation between dose-volume histograms (DVHs) of the intestinal cavity (IC) and moderate-severe acute bowel toxicity in men with prostate cancer treated with pelvic nodal irradiation. Methods and Materials: The study group consisted of 191 patients with localized prostate cancer who underwent whole-pelvis radiotherapy with radical or adjuvant/salvage intent during January 2004 to November 2007. Complete planning/clinical data were available in 175 of these men, 91 of whom were treated with a conventional four-field technique (50.4 Gy, 1.8 Gy/fraction) and 84 of whom were treated with IMRT using conventional Linac (n = 26, 50.4 Gy, 1.8 Gy/fraction) or Helical TomoTherapy (n = 58, 50-54 Gy, 1.8-2 Gy/fraction). The IC outside the planning target volume (PTV) was contoured and the DVH for the first 6 weeks of treatment was recovered in all patients. The correlation between a number of clinical and DVH (V10-V55) variables and toxicity was investigated in univariate and multivariate analyses. The correlation between DVHs for the IC outside the PTV and DVHs for the whole IC was also assessed. Results: Twenty-two patients experienced toxicity (3/22 in the IMRT/tomotherapy group). Univariate analyses showed a significant correlation between V20-V50 and toxicity (p = 0.0002-0.001), with a higher predictive value observed for V40-V50. Previous prostatectomy (p = 0.066) and abdominal/pelvic surgery (p = 0.12) also correlated with toxicity. Multivariate analysis that included V45, abdominal/pelvic surgery, and prostatectomy showed that the most predictive parameters were V45 (p = 0.002) and abdominal/pelvic surgery (p = 0.05, HR = 2.4) Conclusions: Our avoidance IMRT approach drastically reduces the incidence of acute bowel toxicity. V40-V50 of IC and, secondarily, previous abdominal/pelvic surgery were the main predictors of acute bowel toxicity.

  18. An acute toxicity study of Heliotropium scottae Rendle in mice.

    Science.gov (United States)

    Wahome, W M; Muchiri, D J; Mugera, G M

    1994-08-01

    Twenty-four hour ip median lethal doses (LD50) of freeze-dried aqueous extracts of Heliotropium scottae Rendle leaves and stems in mice were determined and clinical signs noted. The LD50 of the leaf extract was 3.0 g/kg, while that of the stems was 3.5 g/kg. Clinical signs were excitement, prostration, rapid breathing, gasping for breath and death. The signs were the same for both the leaf and stem extracts. It was concluded that both the leaves and stems of H scottae have slight acute toxicity.

  19. Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

    Science.gov (United States)

    Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

    2013-09-01

    The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

    International Nuclear Information System (INIS)

    Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

  1. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  2. A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

    International Nuclear Information System (INIS)

    Strigari, Lidia; Pedicini, Piernicola; D’Andrea, Marco; Pinnarò, Paola; Marucci, Laura; Giordano, Carolina; Benassi, Marcello

    2012-01-01

    Purpose: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of ≥G3 AMT. Conclusion: The proposed model is able to predict ≥G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

  3. Acute and substantive action of antimicrobial toothpastes and mouthrinses on oral biofilm in vitro

    NARCIS (Netherlands)

    Otten, Marieke P. T.; Busscher, Henk J.; van der Mei, Henny C.; van Hoogmoed, Chris G.; Abbas, Frank; Hoogmoed, G.G. van

    The aim of this study was to compare acute action by killing or disrupting oral biofilms through the use of antimicrobial toothpastes and mouthrinses in vitro and to investigate substantive action by absorption of antimicrobials in a biofilm. Biofilms from freshly collected human saliva were grown

  4. ProTox: a web server for the in silico prediction of rodent oral toxicity.

    Science.gov (United States)

    Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

    2014-07-01

    Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Acute and chronic aquatic toxicity of aromatic extracts. Summary of relevant test data

    Energy Technology Data Exchange (ETDEWEB)

    Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Leon Paumen, M.; Dmytrasz, B.; Del Castillo, F.

    2013-09-15

    This report describes the experimental procedures and the results obtained in acute and chronic ecotoxicity tests on several aromatic extracts samples. The samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter, Daphnia magna and the algae, Selenastrum capricornutum using water accommodated fractions. These results assist in determining the environmental hazard posed by aromatic extracts.

  6. Impaired Phosphate Tolerance Revealed With an Acute Oral Challenge.

    Science.gov (United States)

    Turner, Mandy E; White, Christine A; Hopman, Wilma M; Ward, Emilie C; Jeronimo, Paul S; Adams, Michael A; Holden, Rachel M

    2018-01-01

    Elevated serum phosphate is consistently linked with cardiovascular disease (CVD) events and mortality in the setting of normal and impaired kidney function. However, serum phosphate does not often exceed the upper limit of normal until glomerular filtration rate (GFR) falls below 30 mL/min/m 2 . It was hypothesized that the response to an oral, bioavailable phosphate load will unmask impaired phosphate tolerance, a maladaptation not revealed by baseline serum phosphate concentrations. In this study, rats with varying kidney function as well as normo-phosphatemic human subjects, with inulin-measured GFR (13.2 to 128.3mL/min), received an oral phosphate load. Hormonal and urinary responses were evaluated over 2 hours. Results revealed that the more rapid elevation of serum phosphate was associated with subjects and rats with higher levels of kidney function, greater responsiveness to acute changes in parathyroid hormone (PTH), and significantly more urinary phosphate at 2 hours. In humans, increases in urinary phosphate to creatinine ratio did not correlate with baseline serum phosphate concentrations but did correlate strongly to early increase of serum phosphate. The blunted rise in serum phosphate in rats with CKD was not the result of altered absorption. This result suggests acute tissue deposition may be altered in the setting of kidney function impairment. Early recognition of impaired phosphate tolerance could translate to important interventions, such as dietary phosphate restriction or phosphate binders, being initiated at much higher levels of kidney function than is current practice. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  7. Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles

    International Nuclear Information System (INIS)

    Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung; Choi, Mina; Cho, Hea-Young; Han, Beom Seok; Kim, Sheen Hee; Kim, Hyoung Ook; Lim, Yong Taik; Chung, Bong Hyun; Jeong, Jayoung

    2009-01-01

    In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have long blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications

  8. Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart. Coville

    Directory of Open Access Journals (Sweden)

    Anna C. Almeida

    Full Text Available ABSTRACT: This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922 and Staphylococcus aureus (ATCC 25923 in the concentration of 200, 400 and 600μL/mL. The results indicated that 600μL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.

  9. Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

    Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

  10. Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

    DEFF Research Database (Denmark)

    Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.

    2017-01-01

    The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60...... % (monkfish). Arsenic (> 64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73 %) and iodine (71 %) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according...

  11. Pharmacologic treatment of acute pediatric methamphetamine toxicity.

    Science.gov (United States)

    Ruha, Anne-Michelle; Yarema, Mark C

    2006-12-01

    To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

  12. Impact of bioavailability on the correlation between in vitro cytotoxic and in vivo acute fish toxic concentrations of chemicals

    International Nuclear Information System (INIS)

    Guelden, Michael; Seibert, Hasso

    2005-01-01

    The lower sensitivity of in vitro cytotoxicity assays currently restricts their use as alternative to the fish acute toxicity assays for hazard assessment of chemicals in the aquatic environment. In vitro cytotoxic potencies mostly refer to nominal concentrations. The main objective of the present study was to investigate, whether a reduced availability of chemicals in vitro can account for the lower sensitivity of in vitro toxicity test systems. For this purpose, the bioavailable free fractions of the nominal cytotoxic concentrations (EC 50 ) of chemicals determined with a cytotoxicity test system using Balb/c 3T3 cells and the corresponding free cytotoxic concentrations (ECu 50 ) were calculated. The algorithm applied is based on a previously developed simple equilibrium distribution model for chemicals in cell cultures with serum-supplemented culture media. This model considers the distribution of chemicals between water, lipids and serum albumin. The algorithm requires the relative lipid volume of the test system, the octanol-water partition coefficient (K ow ) and the in vitro albumin-bound fraction of the chemicals. The latter was determined from EC 50 -measurements in the presence of different albumin concentrations with the Balb/c 3T3 test system. Organic chemicals covering a wide range of cytotoxic potency (EC 50 : 0.16-527000 μM) and lipophilicity (log K ow : -5.0-6.96) were selected, for which fish acute toxicity data (LC 50 -values) from at least one of the three fish species, medaka, rainbow trout and fathead minnow, respectively, were available. The availability of several chemicals was shown to be extensively reduced either by partitioning into lipids or by serum albumin binding, or due to both mechanisms. Reduction of bioavailability became more important with increasing cytotoxic potency. The sensitivity of the Balb/c 3T3 cytotoxicity assay and the correspondence between in vivo and in vitro toxic potencies were increased when the free cytotoxic

  13. A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients

    International Nuclear Information System (INIS)

    Norkus, Darius; Valuckas, Konstantinas Povilas; Karklelyte, Agata; Engels, Benedikt; Versmessen, Harijati; Griskevicius, Romas; De Ridder, Mark; Storme, Guy; Aleknavicius, Eduardas; Janulionis, Ernestas

    2013-01-01

    The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these

  14. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study

    OpenAIRE

    Krymchantowski,Abouch V.; Barbosa,Jackeline S.; Cheim,Celia; Alves,Luiz A.

    2001-01-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, wer...

  15. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    Science.gov (United States)

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

  16. Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

    NARCIS (Netherlands)

    Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; Heuvel, van den Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, António

    2017-01-01

    The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60%

  17. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action.

    Science.gov (United States)

    Sanderson, Hans; Thomsen, Marianne

    2009-06-01

    Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

  18. Acute toxicity of vanadium to the threespine stickleback, Gasterosteus aculeatus

    Energy Technology Data Exchange (ETDEWEB)

    Gravenmier, J.J.; Johnston, D.W.; Arnold, W.R. [Blasland Bouck & Lee Inc, Petaluma, CA (US)

    2005-02-15

    Vanadium is widely distributed, occurring in many types of minerals, coal, and petroleum. Anthropogenic sources of vanadium originate from the production, processing, and wastes of these materials. The aquatic toxicity of vanadium to fish species is not well characterized. This study focused on the three-spined stickleback, Gasterosteus aculeatus, a small and widely distributed euryhaline species of fish. The three-spined stickleback is used as an effluent-monitoring species in both Canada and the United States. Five 96-h static renewal acute toxicity tests were performed in moderately hard water with adult fish. The geometric mean and range of the five 96-h LC{sup 50}s based on measured concentrations of total vanadium in the test solution were 3.17 and 2.35-4.07 mg V/L, respectively. A conservative estimation of a safe concentration of vanadium that would not affect survival of adult three-spined sticklebacks over a 96-h exposure period in moderately hard water is approximately 0.30 mg V/L. A comparison with other fish species previously tested suggests that the three-spined stickleback is intermediate in sensitivity to vanadium. Information reported from this study may be useful in effluent toxicity identification evaluations and ecological risk assessments related to vanadium.

  19. Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

    International Nuclear Information System (INIS)

    Fuma, S.; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G.

    2003-01-01

    The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of γ-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation

  20. Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

    Science.gov (United States)

    Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

    2015-11-01

    The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

  1. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    International Nuclear Information System (INIS)

    Gao, Yongfei; Feng, Jianfeng; Zhu, Lin

    2015-01-01

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H"+. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10"−"6 M Cd and 10"−"6 M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H"+ in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  2. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

    2015-12-15

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  3. The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Shoshana Rudin

    2017-04-01

    Full Text Available Pediatric acute lymphoblastic leukemia (ALL affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP and methotrexate (MTX, are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT, nudix hydrolase 15 (NUDT15, and potentially inosine triphosphatase (ITPA, which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1 and dihydrofolate reductase (DHFR. Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1 and thymidylate synthetase (TYMS, but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

  4. Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

    Science.gov (United States)

    Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

    2012-11-01

    The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

  5. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.1

    Science.gov (United States)

    Predictive toxicological models are integral to ecological risk assessment because data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ge...

  6. Development of a standard acute dietary toxicity test for the silkworm (Bombyx mori L.)

    NARCIS (Netherlands)

    Sun, X.; Valk, H.; Jiang, H.; Wang, X.; Yuan, S.; Zhang, Y.; Roessink, I.; Gao, X.

    2012-01-01

    Larvae of the silkworm (Bombyx mod L.) may be exposed to pesticide residues on the leaves of their food plant, the mulberry tree (Morus spp.), which can lead to adverse effects on silk production. A new acute dietary toxicity test method was evaluated as the basis for pesticide risk assessment. A

  7. Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II-4-(2-5-Bromo-benzylideneaminoethyl Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

    Directory of Open Access Journals (Sweden)

    A. Hamid A. Hadi

    2011-10-01

    Full Text Available The compound dichlorido-copper(II-4-(2-5-bromobenzylideneaminoethyl piperazin-1-ium phenolate (CuLBS was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01. Serum levels of liver enzymes aspartate (AST and alanine transaminases (ALT, pro-inflammatory (IL-6 and TNF-α and anti-inflammatory (IL-10 cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05 protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

  8. Neutral vs positive oral contrast in diagnosing acute appendicitis with contrast-enhanced CT: sensitivity, specificity, reader confidence and interpretation time

    Science.gov (United States)

    Naeger, D M; Chang, S D; Kolli, P; Shah, V; Huang, W; Thoeni, R F

    2011-01-01

    Objective The study compared the sensitivity, specificity, confidence and interpretation time of readers of differing experience in diagnosing acute appendicitis with contrast-enhanced CT using neutral vs positive oral contrast agents. Methods Contrast-enhanced CT for right lower quadrant or right flank pain was performed in 200 patients with neutral and 200 with positive oral contrast including 199 with proven acute appendicitis and 201 with other diagnoses. Test set disease prevalence was 50%. Two experienced gastrointestinal radiologists, one fellow and two first-year residents blindly assessed all studies for appendicitis (2000 readings) and assigned confidence scores (1=poor to 4=excellent). Receiver operating characteristic (ROC) curves were generated. Total interpretation time was recorded. Each reader's interpretation with the two agents was compared using standard statistical methods. Results Average reader sensitivity was found to be 96% (range 91–99%) with positive and 95% (89–98%) with neutral oral contrast; specificity was 96% (92–98%) and 94% (90–97%). For each reader, no statistically significant difference was found between the two agents (sensitivities p-values >0.6; specificities p-values>0.08), in the area under the ROC curve (range 0.95–0.99) or in average interpretation times. In cases without appendicitis, positive oral contrast demonstrated improved appendix identification (average 90% vs 78%) and higher confidence scores for three readers. Average interpretation times showed no statistically significant differences between the agents. Conclusion Neutral vs positive oral contrast does not affect the accuracy of contrast-enhanced CT for diagnosing acute appendicitis. Although positive oral contrast might help to identify normal appendices, we continue to use neutral oral contrast given its other potential benefits. PMID:20959365

  9. Single dose oral flurbiprofen for acute postoperative pain in adults

    Science.gov (United States)

    Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

    2014-01-01

    Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

  10. Oral toxicity of silver ions, silver nanoparticles and colloidal silver--a review.

    Science.gov (United States)

    Hadrup, Niels; Lam, Henrik R

    2014-02-01

    Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Toxicity study about a medicinal plant Casearia sylvestris: A contribution to the Brazilian Unified Health System (SUS).

    Science.gov (United States)

    Ameni, A Z; Latorre, O A; Torres, L M B; Górniak, S L

    2015-12-04

    Casearia sylvestris S.w (Salicaceae) is catalogued by the Brazilian Unified Health System as a plant of interest for the Brazilian population with the purpose of treating inflammatory disorders, such as pain and gastrointestinal disorders based on the folk use and some literature about efficacy; however, no toxicological studies concerned the safety of extract fluid of this plant have been reported. The present study was carried out to evaluate the acute and subchronic toxicity of the hydroethanolic extract fluid (FE) obtained from leaves of C. sylvestris in Wistar rats. In the acute toxicity test three female Wistar rats were treated with a single dose of FE (2000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study animals received, by daily gavage three doses 60, 120 and 240 mg/kg of the FE of the plant for 28 and 90 days. The animals were observed daily for clinical signs and mortality. Body weight and food consumption were measured weekly and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Also was analysed the cellularity of bone marrow and spleen. Moreover, phytochemical analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI was carried out to qualify the constituents of the extract. The results of acute study indicated that the LD50 is higher than 2000 mg/kg and at 28 and 90 day oral toxicity showed that there were no toxic effects detected in any of the parameters evaluated: body weight and relative organ weight, general behavioral changes, haematological and biochemical parameters and histopathological examination. The analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI identified the flavonoids rutin, quercetin and luteolin and also chlorogenic on the extract. Based on this study the hydroethanolic fluid extract of C. sylvestris could be safe even when used over a long period for therapeutic uses proposed by the Brazilian Unified Health

  12. Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

    DEFF Research Database (Denmark)

    Hadrup, Niels; Lam, Henrik Rye

    2014-01-01

    Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

  13. Toxicity levels to humans during acute exposure to hydrogen fluoride

    International Nuclear Information System (INIS)

    Halton, D.M.; Dranitsaris, P.; Baynes, C.J.

    1984-11-01

    A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

  14. Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X. [Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Easson, Alexandra M. [Department of Surgical Oncology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario (Canada); Kassam, Zahra; Cho, Charles [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Kim, John, E-mail: John.Kim@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-11-01

    Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

  15. In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae Leaves

    Directory of Open Access Journals (Sweden)

    Aldilane Gonçalves Fonseca

    2018-01-01

    Full Text Available The species Kalanchoe brasiliensis, known as “Saião,” has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis. The action of the extract (concentrations from 0.1 to 1000 uL/100 uL in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal and 786-0 (kidney carcinoma, showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo, the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

  16. Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae

    Directory of Open Access Journals (Sweden)

    Mildred García-González

    2006-12-01

    Full Text Available We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1 000 and 2 000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week. Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1 000 mg/kg dose but not for the higher 2 000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found. Rev. Biol. Trop. 54 (4: 1323-1326. Epub 2006 Dec. 15Se evaluaron los efectos del estracto acuoso de las hojas de Petiveria alliacea, en la toxicidad aguda y toxicidad subcrónica, hematocritos, niveles de glucosa en la sangre y motilidad intestinal del ratón macho albino NGP, con un peso promedio de 20 a 25g. En todos los casos los tratamientos fueron dosis de 1 000 y 2 000 mg/kg de peso del animal y un tratamiento control con 0.5 ml de agua destilada, usando 10 animales por tratamiento y administrado oralmente cinco días por semana. Los períodos experimentales fueron de 18 y 70 días para toxicidad aguda y toxicidad subcrónica, respectivamente. No se observaron signos de mortalidad ni de toxidad en ambas pruebas. Con la dosis de 1 000 mg/kg hubo un leve pero significativo incremento en los niveles de glucosa durante las primeras tres semanas, pero no con la dosis más alta de 2 000 mg/kg. Después de administrar las dosis luego de un período de hambre de seis horas, no se encontraron diferencias significativas en la motilidad intestinal

  17. Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

    Science.gov (United States)

    The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

  18. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

    International Nuclear Information System (INIS)

    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea; Zapf, Antonia; Pradier, Olivier; Schmidberger, Heinz

    2009-01-01

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  19. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

    Energy Technology Data Exchange (ETDEWEB)

    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

    2009-09-15

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  20. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    Science.gov (United States)

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.