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Sample records for acute oral toxicity

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

    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. PMID:26971557

  2. ACUTE ORAL TOXICITY OF MUCUNA PRURIENS IN SWISS ALBINO MICE

    Parekar Sushant Shahaji; Somkuwar Arju Parnu

    2011-01-01

    Mucuna pruriens, belonging to the botanical family Fabaceae, has been used in traditional Ayurvedic Indian medicine for various ailments including Parkinson’s disease. The current study reports the outcome of acute oral toxicity investigation of ethanolic extract of M. pruriens (whole plant) on Swiss albino mice. No mortalities or evidence of adverse effects have been observed in Swiss albino mice following acute oral administration of ethanolic extract of M. pruriens at the dose of 2000 mg/...

  3. ACUTE ORAL TOXICITY OF MUCUNA PRURIENS IN SWISS ALBINO MICE

    Parekar Sushant Shahaji

    2011-05-01

    Full Text Available Mucuna pruriens, belonging to the botanical family Fabaceae, has been used in traditional Ayurvedic Indian medicine for various ailments including Parkinson’s disease. The current study reports the outcome of acute oral toxicity investigation of ethanolic extract of M. pruriens (whole plant on Swiss albino mice. No mortalities or evidence of adverse effects have been observed in Swiss albino mice following acute oral administration of ethanolic extract of M. pruriens at the dose of 2000 mg/ kg. This is the first report on the acute oral toxicity of M. pruriens and thus the findings of this study provide scientific validation on the use of the M. pruriens as a medicine for treating various ailments.

  4. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

    Xiu Wen P'ng, Gabriel Akyirem Akowuah and Jin Han Chin*

    2012-01-01

    Clinacanthus nutans Lindau (Family: Acanthaceae) has attracted public interest recently due to its high medicinal values for the treatment of cancer, inflammation and various skin problems. This study was aimed to determine the oral LD50 value of the methanol leaves extract of C. nutans and identify the targeted organs in mice. This acute oral toxicity study was conducted in accordance to OECD 423 guidelines by using male Swiss albino mice weighing 25-35 g. First group was served as control g...

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

    Wuen Yew Teoh; Kae Shin Sim; Jaime Stella Moses Richardson; Norhanom Abdul Wahab; See Ziau Hoe

    2013-01-01

    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 adenocarci...

  6. ECVAM's ongoing activities in the area of acute oral toxicity.

    Kinsner-Ovaskainen, Agnieszka; Bulgheroni, Anna; Hartung, Thomas; Prieto, Pilar

    2009-12-01

    The 7th Amendment of the Cosmetics Directive (2003/15/EC) set up timelines for banning animal testing and marketing of cosmetic products and their ingredients tested on animals. For most of the human health effects, including acute toxicity, the deadline for these bans was in March 2009. Moreover, the new Regulation EC 1907/2006 on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) provided a strong impetus towards the application of alternative approaches to reduce the number of animals used for toxicological testing. Therefore, the European Centre for the Validation of Alternative Methods (ECVAM) is currently putting considerable effort into developing and validating alternative methods in the field of acute toxicity. The main activities in this area include: (1) the Integrated Project ACuteTox, funded by the European Commission's 6th Framework Programme in 2005 with the aim to develop and pre-validate a testing strategy to fully replace acute oral toxicity testing in vivo; (2) a follow-up validation study to assess the predictive capacity of the validated BALB/3T3 Neutral Red Uptake cytotoxicity assay to discriminate between toxic/hazardous (LD(50)2,000 mg/kg); (3) an approach to identify compounds with LD(50)>2,000 mg/kg using information from 28-days repeated dose toxicity studies. PMID:19591916

  7. Acute oral toxicities of wildland fire control chemicals to birds

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

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

    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.

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

    Teoh, Wuen Yew; Sim, Kae Shin; Moses Richardson, Jaime Stella; Abdul Wahab, Norhanom; Hoe, See Ziau

    2013-01-01

    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. PMID:24369485

  10. ACUTE ORAL TOXICITY STUDY OF CLINACANTHUS NUTANS IN MICE

    Xiu Wen P'ng, Gabriel Akyirem Akowuah and Jin Han Chin*

    2012-11-01

    Full Text Available Clinacanthus nutans Lindau (Family: Acanthaceae has attracted public interest recently due to its high medicinal values for the treatment of cancer, inflammation and various skin problems. This study was aimed to determine the oral LD50 value of the methanol leaves extract of C. nutans and identify the targeted organs in mice. This acute oral toxicity study was conducted in accordance to OECD 423 guidelines by using male Swiss albino mice weighing 25-35 g. First group was served as control group which received distilled water (vehicle while second and third group were orally treated with single daily dose of 0.9 g/kg and 1.8 g/kg of methanol leaves extract of C. nutans, respectively. All the animals were closely observed for 14 days. Body weight for each mouse was recorded at day-0, day-3, day-7 and day-14. Relative organ weights for liver, kidney, spleen, lung and heart were also determined. All the results were presented as mean ± standard deviation and analyzed using Dunnett’s Test after ANOVA test. From the results obtained, no mortality was observed in both treatment groups either post 24 hours or 14 days of oral administration of C. nutans. Body weight for each mouse and relative organ weight showed insignificant difference when compared to the control group. In conclusion, acute exposure of 1.8 g/kg of C. nutans was safe in male mice without causing any adverse effects or mortality. The oral LD50 of methanol leaves extract of C. nutans was suggested to be greater than 1.8 g/kg bw in male mice.

  11. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  12. Evaluation of Acute and Subacute Oral Toxicity of the Ethanol Extract from Antidesma Acidum Retz.

    Sireeratawong, Seewaboon; Thamaree, Sopit; Ingkaninan, Kornkanok; Piyabhan, Pritsana; Vannasiri, Supaporn; Khonsung, Parirat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    Toxicity tests of 95% ethanol extract of the root of Antidesma acidum were studied in male and female rats. The oral acute toxicity test at 5,000 mg/kg revealed that the ethanol extract did not produce toxic effects on signs, general behavious, mortality and gross appearance of internal organs of rats. Furthermore, the oral sub-acute toxicity test at the dose of 1,000 mg/kg/day displayed no significant changes in body and internal organs' weights, normal hematological and clinical blood chemi...

  13. ADMET evaluation in drug discovery: 15. Accurate prediction of rat oral acute toxicity using relevance vector machine and consensus modeling

    Lei, Tailong; Li, Youyong; Song, Yunlong; Li, Dan; Sun, Huiyong; Hou, Tingjun

    2016-01-01

    Background Determination of acute toxicity, expressed as median lethal dose (LD50), is one of the most important steps in drug discovery pipeline. Because in vivo assays for oral acute toxicity in mammals are time-consuming and costly, there is thus an urgent need to develop in silico prediction models of oral acute toxicity. Results In this study, based on a comprehensive data set containing 7314 diverse chemicals with rat oral LD50 values, relevance vector machine (RVM) technique was employ...

  14. Acute Oral Toxicity and Brine Shrimp Lethality of Elaeis guineensis Jacq., (Oil Palm Leaf) Methanol Extract

    Yeng Chen; Lai Ngit Shin; Yee Ling Lau; Sreenivasan Sasidharan; Yuet Ping Kwan; Lachimanan Yoga Latha; Soundararajan Vijayarathna; Abdul Rani Muhamad Syahmi

    2010-01-01

    Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal be...

  15. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  16. Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats*

    Budin, Siti Balkis; Siti Nor Ain, Seri Masran; Omar, Baharuddin; Taib, Izatus Shima; Hidayatulfathi, Othman

    2012-01-01

    Litsea elliptica Blume has been traditionally used to treat headache, fever, and stomach ulcer, and has also been used as an insect repellent. The acute and subacute toxicities of L. elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats. For the acute toxicity study, L. elliptica essential oil was administered in doses from 500 to 4 000 mg/kg (single dose), and in the subacute toxicity test, the following doses were used: 125, 250, and 500 mg/kg, for 28 consecu...

  17. Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract

    Geethaa Sahgal; Surash Ramanathan; Sreenivasan Sasidharan; Mohd. Nizam Mordi; Sabariah Ismail; Sharif Mahsufi Mansor

    2010-01-01

    Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract. Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice. Results: The brine shrimp lethality bioassay shows a moderate cytotoxicity at high co...

  18. ACUTE AND SUB-CHORONIC ORAL TOXICITY OF ASIATICOSIDE TO MICE

    Uvarajan Sampath

    2012-09-01

    Full Text Available The components in Centellaasiatica (gotukala, vallarai was reported to possess different biological activities in various in vitro and in vivo test models including gastric ulcer healing, wound healing, memory enhancing, immunomodulating effects along with cytotoxic, neuroprotective, antioxidant potential. Asiaticoside is one of the major triterpenoid saponin isolated from Centellaasiatica. Currently, there is no evidence for safety details of asiaticoside in experimental mice. The purpose of this study is to explore the acute and sub-chronic oral toxicities of asiaticoside. Acute oral toxicity study was conducted by giving 300-5000 mgkg-1 bodyweight of asiaticoside and the animals were observed after 1 h administration of the drug and also examined after 14 days of administration for mortality and morbidity.The lethal dose (LD50 was found to greater than 2000 mgkg⁻¹ bodyweight. In sub-chronic oral toxicity studies, the selected oral doses were 200, 500, 1000 mgkg⁻¹and the evaluation was carried out after 90 days of oral administration of asiaticoside. Biochemical, histopathological and hematological changes along with body and relative organ weights of the mice were analysed and significant changes were observed in the mice treated with 1000 mgkg-1 of asiaticoside.. The observed results were statistically analyzed using one way ANOVA which suggested that Asiaticoside does not possess any toxic effect up to 500mg/kg bodyweight and it is best suited for any kind of future application related to its efficacy.

  19. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  20. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

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

    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.

  2. Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.

    Jonsson, Martina; Jestoi, Marika; Nathanail, Alexis V; Kokkonen, Ulla-Maija; Anttila, Marjukka; Koivisto, Pertti; Karhunen, Pirkko; Peltonen, Kimmo

    2013-03-01

    Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health. PMID:23201451

  3. PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ACUTE ORAL TOXICITY STUDY OF MUCUNA PRURIENS LINN. IN ALBINO MICE

    Deka Manalisha; Kalita Jogen Chandra

    2012-01-01

    Mucuna Pruriens Linn. is an annual, climbing shrub which has an important place among aphrodisiac herbs in India since the ancient times. The plant has been using traditionally for many medicinal purposes such as Infertility, Parkinson’s disease, Loss of libido, Antioxidant, Anti venom, Anti microbial etc. The present study was carried out to investigate the preliminary phytochemical analysis and acute oral toxicity of the seeds of M.pruriens on albino mice. Matured seeds of M.pruriens were d...

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

    Chandrasekaran Chinampudur Velusami; Srinivasa Rao Boddapati; Srikanth Hongasandra Srinivasa; Edwin Jothie Richard; Joshua Allan Joseph; Murali Balasubramanian; Amit Agarwal

    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 m...

  5. Acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine.

    Hoffmann, Marc S; Overman, Michael J; Nates, Joseph L

    2016-04-01

    Improvements in antiemetic therapy constitute a major advance in oncology. A recent poll of the oncology community by the American Society of Clinical Oncology ranked it as one of the top 5 advances in cancer in the last 50 years. Emetogenicity of chemotherapy is defined by risk of emesis in the patient given no antiemetics; high-risk regimens cause nausea and vomiting in >90% of patients, moderate risk in 30%-90%, and low risk in <30%. This risk profile serves as the basis for empiric antiemetic prophylaxis and offers alternatives to refractory patients. Modern antiemetic prophylaxis is extremely effective for high-risk chemotherapy, reducing the risk for breakthrough nausea and vomiting to 0%-13% in the acute setting (<24 hours from receipt of chemotherapy) and to 25%-30% in the delayed setting (24-72 hours from receipt of chemotherapy). PMID:27152518

  6. Acute and chronic oral toxicity of a partially purified plaunotol extract from Croton stellatopilosus Ohba.

    Chaotham, Chatchai; Chivapat, Songpol; Chaikitwattana, Anan; De-Eknamkul, Wanchai

    2013-01-01

    Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD₅₀ = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans. PMID:24286075

  7. Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract from Croton stellatopilosus Ohba

    Chatchai Chaotham

    2013-01-01

    Full Text Available Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50=10.25 g/kg. The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day. These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

  8. Acute Oral Toxicity Study of GAL-57 (Bentazon + Dicamba Herbicide in Rats

    Dragica Brkić

    2009-01-01

    Full Text Available An acute oral toxicity study of the herbicide GAL-57 (Avalon, a mixture of bentazon and dicamba as active ingredients, was conducted to assess its acute oral toxicity to rats, using a new method that has been used in the past several years (2001. Clinical observations were performed for all animals after different time intervals, and gross necropsy was performed at termination of examination. Clinical symptoms (decreased activity, prone position, abnormal limb position, decreased righting reflex, decreased grip and limb tone, decreased body and abdominal tone and dyspnoea from mild to marked degree were noted after administration of 2000 mg/kg. Animals were found dead 30 minutes to one hour after the treatment. GAL-57 did not cause any clinical sings at single 300 mg/kg bw dose. The physical condition and behaviour of animals were normal during the 14-day observation period. The acute oral LD-50 value of the GAL-57 proved to be between 300 and 2000 mg/kg body weight in rats and was ranked into Poison group III according to Serbian criteria, category 4 of the Global Harmonized Classification System and Category III of the EPA classification.

  9. Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats

    Siti Balkis BUDIN; Seri Masran SITINOR AIN; Baharuddin OMAR; Izatus Shima TAIB; Othman HIDAYATULFATHI

    2012-01-01

    Litsea elliptica Blume has been traditionally used to treat headache,fever,and stomach ulcer,and has also been used as an insect repellent.The acute and subacute toxicities of L.el/iptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats.For the acute toxicity study,L.e//iptica essential oil was administered in doses from 500 to 4000 mg/kg (single dose),and in the subacute toxicity test,the following doses were used:125,250,and 500 mg/kg,for 28 consecutive days.In the acute toxicity study,L.elliptica essential oil caused dose-dependent adverse behaviours and mortality.The median lethal dose value was 3488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg.The subacute toxicity study of L.elliptica essential oil did not reveal alterations in body weight,and food and water consumptions.The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined,except for the hemoglobin,mean cell hemoglobin concentration,mean cell volume,mean cell hemoglobin,serum albumin,and serum sodium.However,these differences were still within the normal range.No abnormalities or histopathological changes were observed in the liver,pancreatic islet of Langerhans,and renal glomerulous and tubular cells of all treated groups.In conclusion,L.el/iptica essential oil can be classified in the U group,which is defined as a group unlikely to present an acute hazard according to World Health Organization (WHO) classification.

  10. Acute Oral Toxicity and Brine Shrimp Lethality of Elaeis guineensis Jacq., (Oil Palm Leaf Methanol Extract

    Yeng Chen

    2010-11-01

    Full Text Available Elaeis guineensis (Arecaceae is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC50 values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively, confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

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

    Chandrasekaran Chinampudur Velusami

    2013-01-01

    Full Text Available 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.

  12. Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract of Zingiber zerumbet (L.) Smith in Rodents

    Yuan-Shiun Chang; Shorong-Shii Liou; I-Min Liu; Thing-Fong Tzeng; Chia Ju Chang

    2012-01-01

    The objective of this study was to evaluate the acute and subacute toxicity (28 days) of the ethanol extract of Z. zerumbet rhizomes (EEZZ) via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1 of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage...

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

    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)

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

    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>LD50development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. PMID:27208746

  15. Sub-acute oral toxicity study of methanol leaves extract of Catharanthus roseus in rats

    LYW Kevin; AH Hussin; I Zhari; JH Chin

    2012-01-01

    Objective: To examine the sub-acute (14 d) oral toxic effects of methanol leaves extract ofCatharanthus roseus (C. roseus) (Family: Apocynaceae) on liver and kidney functions in Sprague Dawley (SD) rats. Methods: Twenty four female SD rats were used throughout the experiment. The first group was orally treated with distilled water and served as control, whereas the remaining three groups were orally treated with single dose daily of 0.1 g/kg, 0.5 g/kg, 1 g/kg of C. roseus extract, respectively for 14 d. Cage-side observations were done daily. Any animal died during the experiment was dissected for gross organ examination. Body weight changed, food consumption and water intake were recorded weekly. Blood was collected via cardiac puncture on day-15 and used for determination of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. The relative organ weights were also measured. All results were expressed as mean ± S.E.M and analysed using Dunnett’s test. The level of significance was set at P<0.05 when compared to the control group. Results: Repeated oral administration of 0.5 g/kg and 1 g/kg of methanol leaves extract of C. roseus caused mortality and diarrhoea in rats after few days of treatment. There were no significant changes observed in serum biochemical markers, body weight changed, water and food intake and relative organ weight in rats treated with a single dose daily of 0.1 g/kg of C. roseus extract treatment for 14 d when compared to control group. Conclusionds: Fourteen days repeated oral administration of 0.1 g/kg of methanol leaves extract of C. roseus was safe in female SD rats without causing any significant damages to liver and kidney.

  16. Safety Evaluation of Chrysanthemum indicum L. Flower Oil by Assessing Acute Oral Toxicity, Micronucleus Abnormalities, and Mutagenicity

    Hwang, Eun-Sun; Kim, Gun-Hee

    2013-01-01

    Chrysanthemum indicum is widely used to treat immune-related and infectious disorders in East Asia. C. indicum flower oil contains 1,8-cineole, germacrene D, camphor, α-cadinol, camphene, pinocarvone, β-caryophyllene, 3-cyclohexen-1-ol, and γ-curcumene. We evaluated the safety of C. indicum flower oil by conducting acute oral toxicity, bone marrow micronucleus, and bacterial reverse mutation tests. Mortality, clinical signs and gross findings of mice were measured for 15 days after the oral s...

  17. PRELIMINARY PHYTOCHEMICAL SCREENING AND ACUTE ORAL TOXICITY STUDY OF THE FLOWER OF PHLOGACANTHUS THYRSIFLORUS NEES IN ALBINO MICE

    Chakravarty Sharmistha

    2012-04-01

    Full Text Available Medicinal plants contains a variety of chemical substances with important therapeutic properties that can be utilised in the treatment of human diseases. Phlogacanthus thyrsiflorus Nees of family Acanthaceae is used in folklore remedies for treatment of Cough, Bronchitis, Fever, Asthama, Cancer and many other ailments. The present investigation was carried out to assess the qualitative phytochemical analysis of aqueous extract of the flower of Phlogacanthus thyrsiflorus Nees. The phytochemical screening reveals the presence of Tannin, Saponin, Flavonoid, Steroid, Triterpenoid, Phenol. For Acute Oral Toxicity study aqueous extract of the flower was used. The Acute Oral Toxicity test showed no mortality upto 1000 mg/kg body weight. The presence of these phytochemicals reveals its medicinal properties and non toxic nature of the plant indicated the value of the plant as medicine. This result suggests that the flower of Phlogacanthus thyrsiflorus can be used to cure various ailments.

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

    Yamisleydi Alonso Moreno; Yoagne María Trapero Quintana

    2008-01-01

    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 macho...

  19. Acute Oral Toxicity Studies of Ethanol Leaf Extracts Of Derris Scandens & Pulicaria Wightiana In Albino Rats

    Vidya Sabbani

    2015-02-01

    Full Text Available Objective: The present study was designed to find out LD50 and to ascertain the safety of ethanol extracts of leaves of Derris scan dens and Pulicaria wightiana by acute oral toxicity study in female rats as per OECD guideline 425.Methods: Rats were sequentially administered with ethanol leaf extracts of Derris scandens (Ds & Pulicaria wightiana(Pw  in single dosages of 175, 550, and 2000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters and body weight for 14 days.Results: No mortality and no significant changes were observed in body weight and wellness parameters at 175, 550 and 2000 mg/kg body wt. doses of both Derris scandens and Pulicaria wightiana , which reveal the safety of these plants  in the doses up to 2000 mg/kg body weight.Conclusion: Conclusively, LD50 value of ethanol extracts of leaves of Derris scandens and Pulicaria wightiana were found to be more than 2000 mg/kg body weight.

  20. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, Domain of Application and Prediction

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-01-01

    International audience Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and...

  1. EURL ECVAM Recommendation on the 3T3 Neutral Red Uptake Cytotoxicity Assay for Acute Oral Toxicity Testing

    PRIETO PERAITA Maria Del Pilar; GRIESINGER Claudius; AMCOFF SVEN PATRIK; Whelan, Maurice

    2013-01-01

    Acute oral toxicity is currently being assessed by a suite of refinement test methods based on the traditional LD50 lethality test and is, besides skin sensitisation, the only remaining animal test required under REACH Annex VII. In view of assessing the use of alternatives for this health endpoint, EURL ECVAM conducted a study on the 3T3 Neutral Red Uptake cytotoxicity test method addressing the method's capacity to support specifically the identification substances not requiring classificat...

  2. Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract from Croton stellatopilosus Ohba

    Chatchai Chaotham; Songpol Chivapat; Anan Chaikitwattana; Wanchai De-Eknamkul

    2013-01-01

    Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol re...

  3. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P<0.05 and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  4. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    Ramgopal Mopuri; Balaji Meriga

    2014-01-01

    Objective: To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T.paniculata) ethanolic extract in Sprague Dawley rats. Methods: The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results:Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions:Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

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

    Rasuli Farhang; Rafie Javad Nazemi; Sadeghi Amin

    2015-01-01

    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: (p...

  6. Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies.

    Liu, Xin; Zheng, Liangqing; Zhang, Rong; Liu, Gang; Xiao, Shensheng; Qiao, Xiaoting; Wu, Yongning; Gong, Zhiyong

    2016-06-01

    Nε-(carboxymethyl)lysine (CML) as a novel potential noxious compound in various food products has aroused extensive concern in recent years. This study aimed to investigate the oral acute and subacute toxicity of CML in mice as per OECD 420 and 407 guidelines. Acute administration of 2000 and 5000 mg/kg CML did not induce any mortality within 14 days, nevertheless some toxicological symptoms and histopathological changes were observed. The estimated LD50 of CML was >5000 mg/kg. In subacute toxicity test, CML was dosed at 200, 500 and 1000 mg/kg in both genders for 28 days. The body weights reduced which was accompanied with the decrease of food consumptions. Hematology parameters viz. RBC, HGB and MCH showed minor alteration but these were still within normal range. Biochemical analysis of hepatic and renal function markers showed significant elevating in AST, ALT, Cr and BUN etc. Histopathological alterations were observed in lung, liver, kidney and spleen. Subacute toxicity of CML involved oxidative stress caused by reducing antioxidant enzyme (SOD and GSH-Px) activities, and significantly increasing lipid peroxide (MDA) level. In conclusion, CML was unlikely to present an acute hazard, but repeated administration could produce deleterious effects on mice especially inducing liver and kidney damage through oxidative stress. PMID:26921796

  7. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    Madhu Katyayani Balijepalli

    2015-01-01

    Full Text Available Background: Swietenia macrophylla King. (Meliaceae seeds (SMS; commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS at a single-dose oral administration of 2 g/kg body weight (bw in sprague dawley (SD rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats′ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach; the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats.

  8. Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract of Zingiber zerumbet (L. Smith in Rodents

    Chia Ju Chang

    2012-01-01

    Full Text Available The objective of this study was to evaluate the acute and subacute toxicity (28 days of the ethanol extract of Z. zerumbet rhizomes (EEZZ via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1 of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ 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. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg−1 for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe.

  9. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides. PMID:26513561

  10. Evaluation of the acute and subchronic oral toxicity of ethanol extract from Valeriana pavonii species in Wistar rats

    María Del Pilar Olaya

    2010-10-01

    Full Text Available Introduction: One of the most frequent problems found in medicinal plants is the absence of clinical, toxicological, and pharmacological studies. Valeriana pavonii is one of the species used in Colombia as an anxiolytic.  Further study of this specie is rendered to add information in the toxicological area. Objective: The acute and subchronic oral toxicity of V. pavonii ethanolic extract was evaluated in Wistar rats of both sexes. Materials and methods: The rats were distributed into four groups: the control group received the vehicle (0.5 mL/100 g of corporal weight and the other three groups received increasing levels of the dosage for 90 days to evaluate characteristics like physical exam, laboratory test (blood chemistry and  haematology, and anatomopathological findings. Results: This study reveals that there were no signs of toxicity, mortality, or significant alterations attributable to the ethanolic extract of V. pavonii. Conclusions: The Not Observed Adverse Effect Levels (NOAEL of V. pavonii ethanolic extract were 2000 and 1000 mg/kg of body weight for the acute and subchronic toxicity studies, respectively.

  11. Evaluation of the acute and subchronic oral toxicity of ethanol extract from Valeriana pavonii species in Wistar rats

    Mario Francisco Guerrero

    2010-09-01

    Full Text Available Introduction: One of the most frequent problems found in medicinal plants is the absence of clinical, toxicological, and pharmacological studies. Valeriana pavonii is one of the species used in Colombia as an anxiolytic. Further study of this specie is rendered to add information in the toxicological area.Objective: The acute and subchronic oral toxicity of V. pavonii ethanolic extract was evaluated in Wistar rats of both sexes.Materials and methods: The rats were distributed into four groups: the control group received the vehicle (0.5 mL/100 g of corporal weight and the other three groups received increasing levels of the dosage for 90 days to evaluate characteristics like physical exam, laboratory test (blood chemistry and haematology, and anatomopathological findings.Results: This study reveals that there were no signs of toxicity, mortality, or significant alterations attributable to the ethanolic extract of V. pavonii.Conclusions: The Not Observed Adverse Effect Levels (NOAEL of V. pavonii ethanolic extract were 2000 and 1000 mg/kg of body weight for the acute and subchronic toxicity studies, respectively.

  12. Acute and sub-acute oral toxicity assessment of the methanolic extract from leaves of Hibiscus rosa-sinensis L. in mice

    Purobi Nath

    2015-03-01

    Background: The leaves of Hibiscus rosa-sinensis L. (Malvaceae are used for the treatment of dysentery and diarrhoea, to promote draining of abscesses and as analgesic agent in the traditional medicine of Cook Islands, Haiti, Japan and Mexico. Aim: The present study investigated the oral acute and subacute toxicity of methanol leaf extract of H. rosa-sinensis in mice. Methods: In the acute toxicity study, a single oral dose of 2000 mg/kg of extract was given to five mice at 48 h intervals. Animals were observed individually for any clinical signs of toxicity or mortality for 14 days. In the sub-acute toxicity study, mice were treated with 400 mg/kg and 800 mg/kg doses of extract for 14 days. The haematological and biochemical parameters and histopathology of liver and kidney of animals were studied at the end of experiment. Results: For acute treatment, the extract did not revealed any signs of toxicity or mortality in any animal, during the 14-days observation period. The LD50 of extract was estimated to be greater than 2000 mg/kg. In the sub-acute toxicity study, administration of 400 mg/kg and 800 mg/kg doses of extract to mice for two weeks did not revealed any marked adverse effects on haematological, biochemical parameters and histopathology of liver and kidney in the 400 mg/kg group. But, hepato-renal toxicity as evidenced by elevations of alanine aminotransferase (ALT, aspartate aminotranferase (AST, total and indirect bilirubin, urea and creatinine was seen in the animals that received 800 mg/kg doe of extract for 14 days. In addition, in the same group of animals, the histological assessments of liver and kidney also showed various adverse effects viz. dilated sinusoids, apoptotic nuclei and inflammatory infiltrate inside sinusoidal capillaries in the liver, and marked disorganization of tubules and glomeruli, and enlarged interstitial spaces in the kidney. Conclusion: The results of this study suggest that for traditional medicine purpose only a low dose

  13. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-01-01

    Layered double hydroxide (LDH) is an inorganic–organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interes...

  14. Evaluation of the sub-acute oral toxic effect of methanol extract of Clinacanthus nutans leaves in rats

    Xiu Wen P’ng; Gabriel Akyrem Akowuah; Jin Han Chin

    2013-01-01

    Objective: To examine the possible sub-acute toxic effect after 14 d oral administration with 0.3 g/kg, 0.6 g/kg and 0.9 g/kg of methanol leaves extract of Clinacanthus nutans (C. nutans) on liver and kidney functions in young male Sprague Dawley (SD) rats. Methods: This study was carried out according to OECD 407 guideline. A total of 24 young healthy male SD rats aged between 8-12 weeks old were used throughout the experiments. Each group consisted of six rats (n=6). All animals were observed twice daily until day-14. Body weight, food consumption and water intake were measured on day-3, 7 and day-14. Blood samples were collected and used to analyse the serum levels of AST, ALT, ALP, bilirubins, urea and creatinine in rats. Relative organ weights for liver, kidney, heart, spleen and lung were calculated. Results: From the results obtained, all the serum biochemical parameters, food and water intake, relative organs weight showed no significant changes when compared to the control group. No lethality and abnormal behavioural changes were seen in both control and treatment groups during experiment.Conclusions: For conclusion, repeatedly dosing of C. nutans extract at 0.3g/kg, 0.6g/kg and 0.9 g/kg up to 14 d was proven safe in male SD rats without causing any adverse effects and organ damages in male SD rats.

  15. PRELIMINARY PHYTOCHEMICAL ANALYSIS AND ACUTE ORAL TOXICITY STUDY OF CLITORIA TERNATEA LINN. ROOTS IN ALBINO MICE

    Deka Manalisha; Kalita Jogen Chandra

    2011-01-01

    Clitoria ternatea has been using since the ancient times for its medicinal values. Almost all the parts of the plant have medicinal property. The root of the plant is reported to have anti diarrheal, Anti histamic, cholinergic activity etc. Traditionally the root has been using for the treatment of many diseases like leucorrhoea, diarrhea, urinary problems, diuretic, impotency, stomach trouble etc. The present study was designed to investigate the preliminary phytochemical analysis and acute ...

  16. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    Madhu Katyayani Balijepalli; Velan Suppaiah; An-me Chin; Ayuba Sunday Buru; Sreenivasa Rao Sagineedu; Mallikarjuna Rao Pichika

    2015-01-01

    Background: Swietenia macrophylla King. (Meliaceae) seeds (SMS); commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS) at a single-dose oral administration of 2 g/kg body weight (bw) in sprague dawley (SD) rats. Materials and Methods: Eight-...

  17. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  18. Acute and subacute oral toxicity study on the flavonoid rich fraction of Monodora tenuifolia seed in albino rats

    Raphael Chukwuma Ekeanyanwu; Obioma Uzoma Njoku

    2014-01-01

    Objective:To investigate the effects of the flavonoid rich fraction of Monodora tenuifolia seed on the haematology, histopathology and liver profile of Wistar albino rats. Methods:Toxicity study was investigated on the flavonoid rich fraction of Monodora tenuifolia in rats administered different concentrations orally for 28 d using standard laboratory procedures. Results:The LD50 of the flavonoid rich fraction was found to be above 5 000 mg/kg body weight in mice observed for 48 h. After the Day 14, biochemical markers of liver injury such as serum alanine aminotransferase, and aspartate aminotransferase decreased significantly (P0.05). There was non-significant (P>0.05) effect observed across the groups in the levels of serum total protein, albumin, globulin, urea and creatinine. The result of histological examination showed various degrees of peribiliary hepatitis after the Day 14 which fizzled out after the Day 28. Conclusions:The result therefore suggests that the seed extract is potentially safe.

  19. Acute Methylenedioxypyrovalerone Toxicity.

    Froberg, Blake A; Levine, Michael; Beuhler, Michael C; Judge, Bryan S; Moore, Philip W; Engebretsen, Kristin M; Mckeown, Nathanael J; Rosenbaum, Christopher D; Young, Amy C; Rusyniak, Daniel E

    2015-06-01

    The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation. PMID:25468313

  20. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  1. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg-1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  2. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  3. ACUTE AND SUBCHRONIC TOXICITY OF MULBERRY FRUITS

    Jintanaporn Wattanathorn

    2012-01-01

    Full Text Available At present, the application of phytomedicine worldwide is substantial increase. The data of the acute and subchronic toxicity studies on medicinal plants or fruits and vegetables used for medicinal purposes should be obtained in order to increase the confidence in its safety to human, particularly for the application as functional food. Despite the widely consumption of mulberry (Morus alba L, Maraceae family fruits both as fruit and as medicine, no systematic evaluation of the toxicity of mulberry fruits is available until now. This study aimed to determine the acute and subchronic oral toxicities of mulberry fruits in male and female Wistar rats. A single acute mulberry fruits extract dose of 2000 mg kg-1 dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 2, 10 and 500 mg kg-1 day-1 were also administered the same way for 90 days. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights and histopathological examinations. In addition, we also examined hematological and clinical chemistry values. The results showed no abnormalities in treated groups as compared to the controls. Although significantly different BUN and glucose were also observed, all of the values were within normal limits. Neither gross abnormalities nor histopathological changes were observed. The results suggest that mulberry fruits do not produce acute or subchronic toxicity in either female or male rats. Therefore mulberry fruits have the potential to be use as functional food. However, a chronic toxicity study should be further carried out to assure the safety for repetitive administration of this fruit before the application of functional food.

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

    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.

  5. QSAR modeling of acute toxicity on mammals caused by aromatic compounds: the case study using oral LD50 for rats.

    Rasulev, Bakhtiyor; Kusić, Hrvoje; Leszczynska, Danuta; Leszczynski, Jerzy; Koprivanac, Natalija

    2010-05-01

    The goal of the study was to predict toxicity in vivo caused by aromatic compounds structured with a single benzene ring and the presence or absence of different substituent groups such as hydroxyl-, nitro-, amino-, methyl-, methoxy-, etc., by using QSAR/QSPR tools. A Genetic Algorithm and multiple regression analysis were applied to select the descriptors and to generate the correlation models. The most predictive model is shown to be the 3-variable model which also has a good ratio of the number of descriptors and their predictive ability to avoid overfitting. The main contributions to the toxicity were shown to be the polarizability weighted MATS2p and the number of certain groups C-026 descriptors. The GA-MLRA approach showed good results in this study, which allows the building of a simple, interpretable and transparent model that can be used for future studies of predicting toxicity of organic compounds to mammals. PMID:21491673

  6. Oral manifestations of acute leukaemia

    Ivanović Mirjana

    2011-01-01

    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  7. Preliminary acute toxicity study on imidacloprid in Swiss albino mice

    Preeti Bagri; Vinod Kumar; Anil Kumar Sikka; Joginder Singh Punia

    2013-01-01

    Aim: To ascertain the maximum tolerated dose (MTD) and to investigate the acute oral toxic effects of imidacloprid towards Swiss albino male mice.Materials and Methods: The MTD of imidacloprid was determined in pilot dose range finding study following the standard method. Animals were observed for toxic signs and symptoms after oral administration of MTD of imidacloprid in single dose. The body weights of animals were recorded on alternate day. Animals were sacrificed on 14th day and changes ...

  8. Assessment of the predictive capacity of the 3T3 Neutral Red Uptake cytotoxicity test method to identify substances not classified for acute oral toxicity (LD50>2000 mg/kg): results of an ECVAM validation study.

    Prieto, Pilar; Cole, Thomas; Curren, Rodger; Gibson, Rosemary M; Liebsch, Manfred; Raabe, Hans; Tuomainen, Anita M; Whelan, Maurice; Kinsner-Ovaskainen, Agnieszka

    2013-04-01

    Assessing chemicals for acute oral toxicity is a standard information requirement of regulatory testing. However, animal testing is now prohibited in the cosmetics sector in Europe, and strongly discouraged for industrial chemicals. Building on the results of a previous international validation study, a follow up study was organised to assess if the 3T3 Neutral Red Uptake cytotoxicity assay could identify substances not requiring classification as acute oral toxicants under the EU regulations. Fifty-six coded industrial chemicals were tested in three laboratories, each using one of the following protocols: the previously validated protocol, an abbreviated version of the protocol and the protocol adapted for an automation platform. Predictions were very similar among the three laboratories. The assay exhibited high sensitivity (92-96%) but relatively low specificity (40-44%). Three chemicals were under predicted. Assuming that most industrial chemicals are not likely to be acutely toxic, this test method could prove a valuable component of an integrated testing strategy, a read-across argument, or weight-of-evidence approach to identify non toxic chemicals (LD50>2000 mg/kg). However, it is likely to under predict chemicals acting via specific mechanisms of action not captured by the 3T3 test system, or which first require biotransformation in vivo. PMID:23246604

  9. 40 CFR 798.2650 - Oral toxicity.

    2010-07-01

    ... (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2650 Oral toxicity. (a) Purpose. In... testing. The subchronic oral study has been designed to permit the determination of the no-observed-effect... experimental animals to a chemical by the oral route for a part (approximately 10 percent) of a life span....

  10. Acute and chronic arsenic toxicity

    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...

  11. Acute and subchronic toxicity of sucralose.

    Goldsmith, L A

    2000-01-01

    The toxicity of sucralose has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female mice and male rats documented no deaths or treatment-related signs at doses of 16g/kg for mice and 10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8 weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794-6406. There were no toxicologically significant effects observed at the 1.0% or 2.5% dietary levels. However, decreases in food consumption, body weight gain and selected organ weights and ratios as well as splenic and thymic histopathologic changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and female rats for 26 weeks investigated further the observations from the dietary study as well as general subchronic toxicity. The gavage study documented no sucralose-related toxicity. These results implicate the reduced palatability and digestibility of diets containing high concentrations of sucralose seen in the diet study as the cause for the decreased food consumption and other accompanying alterations. Dose selection for chronic toxicity studies in rats took into consideration the effect of high concentrations of sucralose on digestion and food consumption and the limitations that would be imposed on subsequent studies. In male and female dogs, no sucralose-related adverse effects were observed following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving doses of approximately 90, 300 and 900mg/kg/day respectively. These studies establish that sucralose is non-toxic in rodents following acute oral administration. The rat no-observed-adverse-effect level ranged between 2.5 and 5.0% following subchronic dietary administration. A 3.0% dietary concentration equivalent to a dose of 900mg

  12. Acute toxicity of pinnatoxins E, F and G to mice.

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  13. Acute toxicity of oil sands wastewater: A toxic balance

    A study was conducted to identify and determine the relative importance of the acutely toxic fractions of wastewater from oil sands extraction using a bioassay directed toxicity identification evaluation (TIE), to use these data to construct a toxic balance, and to determine whether the same fractions were acutely toxic to Microtox, Daphnia, and rainbow trout. Samples of extraction wastewater were obtained from the Mildred Lake tailings pond in Alberta during summer 1991 and 1992. The samples were centrifuged to remove suspended solids and the toxicity of the supernatant was evaluated. Seven manipulations, each of which was designed to remove a different class of compounds, was performed on the supernatant samples. A complete TIE was performed using the Microtox bacterial bioassay. All acute toxicity of the surface tailings pond water to Microtox was removed by precipitation of organic acids or by removal of nonpolar organics. These results suggest that the main toxic fraction was a surfactant. In the interstitial water of the fine tails, volatiles accounted for 15% of the acute toxicity. However, all the acute toxicity of interstitial water was removed by precipitation of organic acids or by removal of nonpolar organics. Organic acids accounted for all the acute toxicity of tailings pond water to Daphnia and rainbow trout. Differences in relative sensitivity of test organisms to the toxic fraction demonstrate the importance of using more than one test organism to evaluate acute toxicity. Daphnia was 0.4 times less sensitive and rainbow trout 3 times more sensitive than Microtox. 20 refs., 6 tabs

  14. ACUTE TOXICITY STUDY OF TOMATO POMACE EXTRACT IN RODENT

    Wathita Phachonpai; Supaporn Muchimapura; Terdthai Tong-Un; Jintanaporn Wattanathorn; Wipawee Thukhammee; Chonlathip Thipkaew; Bungorn Sripanidkulchai; Panakaporn Wannanon

    2013-01-01

    Tomato and tomato products are considered to be healthy food for the human diet. Although tomatoes have been widely studied for their phenolic content, less emphasize has been laid on toxicological effect of this plant. Thus, the purpose of the present study is to determine the acute toxicity effect of Lycopersicon esculentum, or commonly known as tomato, was administered orally in the form of dried tomato pomace extract in vivo. Adult male rats were orally administrated single dose of 1000 a...

  15. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    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.

  16. Acute toxicity of seeds of the sapodilla (Achras sapota L.).

    Singh, P D; Simon, W R; West, M E

    1984-01-01

    An aqueous extract of the sapodilla seed (Achras sapota L.) was acutely toxic to mice and rats (i.p. LD50 = 190 and 250 mg/kg, respectively) with symptoms of dyspnoea, apnoea and convulsions. Soxhlet extraction and chromatographic separation of the seed constituents yielded a brown amorphous solid containing saponin. This was heat-stable and toxic by the i.p. route (LD50 = 30-50 mg/kg) but non-toxic by the oral route in mice and rats. It is proposed that the toxicity of the sapodilla seed is due mainly to the saponin content. PMID:6719472

  17. Oral toxicity of Madhuca butyracea Macb. saponins to albino rats.

    Lalitha, T; Vishwanatha, S; Venkataraman, L V

    1990-07-01

    Saponins, isolated from M. butyracea, were assessed for their acute and subacute oral toxicity in albino rats. Acute doses of saponins caused mortalities and LD50 and LD90 values were 330 and 430 mg/kg body wt respectively. Severe diarrhoea, restlessness and histopathological changes were observed in liver and kidney. Diets containing saponins at 0,250,500 and 1000 ppm for 14 weeks did not affect food intake, growth or organ weights, but induced mild histological changes in liver and kidney and altered the serum levels of alkaline phosphatase, blood urea nitrogen, cholesterol and proteins, particularly in female rats. PMID:2272650

  18. Acute methanol toxicity in minipigs

    Dorman, D.C.; Dye, J.A.; Nassise, M.P.; Ekuta, J.; Bolon, B.

    1993-01-01

    The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.

  19. The Acute Oral Toxicity of 300 Formulated Pesticides to Apis mellifera%300个农药制剂对蜜蜂的急性经口毒性

    赵帅; 袁善奎; 才冰; 姜辉; 王晓军; 林荣华; 瞿唯钢; 张招荣

    2011-01-01

    [Aims] Honey bee is one of the most important insects for plant pollination, but the honey bees are underlying the phenomenon of colony collapse disorder (CCD), one of the factors causing this problem is the much use of pesticides in agricultural production. Totally 300 pesticides were tested for their acute omi toxicity to honey bee (Apis mellifera) by dietary method in the paper, the objective of this study is to understand the status of toxicity of common used pesticides.[Restults] The results indicated that the pesticides with very high toxicity, high toxicity, moderate toxicity and low toxicity pesticides accounted for 14.7, 35.6, 10.7, 39% respectively, the high toxic and very high toxic pesticide covered more than 50%, and these pesticides were mainly the insecticides, while the fungicides and herbicides with relative low toxicity.The toxicity of different pesticide formulations with the same active ingredients (AI) to zebra fish maybe varied for the difference in AI content, formulation type and processing technique. Regarding to the biological pesticides, some of them still have high toxicity to honeybee. [Conclusions] These results suggested that the pesticides with high toxicity to honey bee covered a large proportion of common used pesticides in China, therefore, some precautions should be involved as we used the pesticides, particularly for insecticides to reduce or avoid the side effects on honey bee.%[目的]蜜蜂是一种重要的传粉昆虫,近年来世界各地出现了严重的种群衰退现象,原因之一是农业生产过程中使用了大量农药.采用摄入法测定f300个农药制剂对蜜蜂的急性经口毒性,旨在了解我国常用农药对蜜蜂的毒风险情况.[结果]结果表明:对蜜蜂的急性经口毒性表现剧毒、高毒、中毒、低毒的农药制剂分别占14.7%、35.6%、10.7%、39%,高毒和剧毒农药产品达50%以上,但这些制剂主要为杀虫剂,占整个杀虫剂的74.1%,杀菌剂和除草剂

  20. ACUTE TOXICITY STUDY FOR TINOSPORA CORDIFOLIA

    Shirish Sadashiv Pingale

    2011-05-01

    Full Text Available The aim of the present work is to examine acute toxicity studies for decoction of aerial parts (leaves and stem as well as whole plant powder of Tinospora cordifolia in the form of aqueous slurry as per OECD guidelines in Swiss mice weighing 35 to 45gm. The dose of 3, 5, 7 and 9 ml per kg body weight of decoction and 2, 4, 6 and 8 gm/kg body weight of the whole plant powder were administered orally. All the groups of animals were almost continuously observed for mortality and behavioral changes during first 24 hrs and then daily for a fortnight. The observations of behavioral changes and changes in body weight, food and water intake as well as cage side observations were reported. There was no abnormality observed in all groups. The decoction of fresh leaves and stem as well as whole plant powder have no any significant toxic effect in Swiss mice and the plant material was found to be nontoxic.

  1. Acute toxicity of gasoline and some additives.

    Reese, E.; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these ch...

  2. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts. PMID:11695884

  3. 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

    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

  4. Assessment of acute and subchronic oral toxicity of ethanolic extract of Pothomorphe umbellata L. Miq (Pariparoba Avaliação da toxidade oral aguda e subcrônica de extrato etanólico de Pothomorphe umbellata L. Miq. (Parapiroba

    Sonia Barros

    2005-03-01

    Full Text Available There is a high degree of concern regarding the secure use of plant extracts and, for this very reason, preclinical and clinic toxicological evaluation of these extracts are needed. With the aim to assure the quality and the safety of the extract and due to the scarcity of literature information about Pariparoba extract toxicity, our purpose was to investigate the acute and subchronic toxicity of the standardized ethanolic dried root extract of Pothomorphe umbellata L. Miq. This extract was administered orally to adult swiss mice and wistar rats and the mutagenic potencial of the extract was also evaluated. The extract showed to be non toxic.Existe uma grande preocupação quanto ao uso seguro de extratos vegetais e, por esta razão, a necessidade de estudos toxicológicos pré-clínicos e clínicos destes extratos. O objetivo deste trabalho foi o de avaliar a toxicidade aguda e subcrônica do extrato hidroalcoólico liofilizado de Pothomorphe umbellata L. Miq., administrado por via oral para animais de laboratório. O potencial mutagênico do extrato foi também avaliado pelo teste do micronúcleo. Os resultados dos estudos a curto e médio prazo demonstraram que o extrato não apresenta propriedades tóxicas.

  5. Mechanisms of acute cocaine toxicity

    Heard, Kennon; Palmer, Robert; Zahniser, Nancy R.

    2008-01-01

    Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporters, neurotransmitter receptors and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine an...

  6. Acute Toxicity Study and Antipyretic Effect of the Brown Alga Turbinaria Conoides (J. Agardh) Kuetz

    Kumar, S Sadish; Kumar, Y; Khan, M. S. Y; J Anbu; Sam, K G

    2009-01-01

    The active principles of brown alga, Turbinaria conoides (J.Agardh) Kuetz. (Sargassaceae) was extracted with n-hexane, cyclohexane, methanol and ethanol-water (1:1) and investigated for acute toxicity and antipyretic activity. Phytochemical analysis of the extracts revealed the presence of steroids, flavonoids and reducing sugars. Acute toxicity study was performed in Wistar rats after administration of extracts orally. No mortality was observed up to the dose of 5g/kg for methanol and ethano...

  7. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements. PMID:20144136

  8. Phytochemical and acute toxicity studies of ethanol extract from Pedada (Sonneratia caseolaris) fruit flour (PFF)

    Jariyah Jariyah; Simon B Widjanarko; Yunianta Yunianta; T. Estiasih

    2015-01-01

    Studies on the phytochemical and acute toxicity of pedada fruit flour (PFF) were carried out. In acute toxicity test, oral administration of the extract to Swiss albino mice at four levels dose, i.e. 0, 10.50; 15.75 and 21.00 g/kg body weight.  Phytochemical analysis of the ethanol extract of PFF showed the presence of saponins, sapogenins, terpenoids, flavonoids, tannins,  polyphenols. Phytochemicals such as alkaloids were not detected. The results of acute toxicity (LD50) showed that the et...

  9. Preliminary acute toxicity study on imidacloprid in Swiss albino mice

    Preeti Bagri

    2013-12-01

    Full Text Available Aim: To ascertain the maximum tolerated dose (MTD and to investigate the acute oral toxic effects of imidacloprid towards Swiss albino male mice.Materials and Methods: The MTD of imidacloprid was determined in pilot dose range finding study following the standard method. Animals were observed for toxic signs and symptoms after oral administration of MTD of imidacloprid in single dose. The body weights of animals were recorded on alternate day. Animals were sacrificed on 14th day and changes in hematological parameters (Hb, TEC, TLC and DLC and morphometric measurements (length, breadth, thickness and weight of various body organs (heart, liver, spleen, kidney, testis and epididymis were examined. The student's t-test was applied to statistically analyze the results.Results: The MTD of imidacloprid was determined to be 110 mg/kg body weight. The sign and symptoms of acute toxicity were ataxia, rigidity and fasciculation of muscles, protrusion of eye ball and tremors of head. Imidacloprid treatment resulted in decreased body weight gain as compared to the control group. The changes in hematological parameters were not significant between imidacloprid treated and control groups. Also the values of relative organ weights and morphometric measurements of various body organs did not differ significantly between the control and imidacloprid treated animals.Conclusions: MTD of imidacloprid in Swiss albino male mice through oral route was determined for the first time. Study revealed a non-toxic effect of imidacloprid on body weight, relative organs weight, hematological parameters and morphometric measurements of various body organs in mice.

  10. A Tutorial for Analysing the Cost-effectiveness of Alternative Methods for Assessing Chemical Toxicology: The Case of Acute Oral Toxicity Prediction

    NORLEN H.; Worth, A.P.; Gabbert, S.G.M.

    2014-01-01

    Compared with traditional animal methods for toxicity testing, in vitro and in silico methods are widely considered to permit a more cost-effective assessment of chemicals. However, how to assess the cost-effectiveness of alternative methods has remained unclear. This paper offers a user-oriented tutorial for applying cost-effectiveness analysis (CEA) to alternative (non-animal) methods. The purpose is to illustrate how CEA facilitates the identification of the alternative method, or the comb...

  11. Acute inhalation toxicity of carbonyl sulfide

    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).

  12. ACUTE TOXICITY STUDY OF TOMATO POMACE EXTRACT IN RODENT

    Wathita Phachonpai

    2013-01-01

    Full Text Available Tomato and tomato products are considered to be healthy food for the human diet. Although tomatoes have been widely studied for their phenolic content, less emphasize has been laid on toxicological effect of this plant. Thus, the purpose of the present study is to determine the acute toxicity effect of Lycopersicon esculentum, or commonly known as tomato, was administered orally in the form of dried tomato pomace extract in vivo. Adult male rats were orally administrated single dose of 1000 and 5000 mg kg-1 dried tomato pomace extract. There were 10 rats in each group. All animals were sacrificed after 2 weeks of treatment. Seven parameters were tested: cage side observation, body weight gain measurement, food and water consumption, absolute organ weight, hematology, biochemical analysis and histopathology, to look for evidence of acute toxicity. No mortality was observed when varying doses of the extracts were administered per day for a period of 2 weeks. There were no significant differences in body weight, behavior, food consumption, absolute organ weights between controls and treated animals. Hematological analysis showed no differences in most parameters examined. In the biochemistry parameter measurement, no significant change occurred. Pathologically, neither gross abnormalities nor histopathological changes were observed. These finding suggest that none of the organs appeared to be target and the data could provide satisfactory preclinical evidence of safety to launch clinical trial on standardized formulation of tomato pomace extracts to be the dietary supplement.

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

    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. PMID:22886451

  14. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    Gui Mi Ko; Adela Rosenkranz; Clélia Rejane Antonio Bertoncini; Neide Hyppolito Jurkiewicz; Mirian Ghiraldini Franco; Aron Jurkiewicz

    2010-01-01

    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...

  15. Oral rehydration therapy of acute enteric infections

    S. M. Zacharenko

    2014-09-01

    Full Text Available Analysis of holding rehydration therapy in acute intestinal infections in both civilian and military care facilities showed that the civilian centers of this type of therapy was appointed by 84,5% of patients, and in the military – 50,16%. The average duration of oral rehydration therapy was 4,0 days at the easy degree of weight, at middle – 5,3 and at a heavy flow – 5,7 days. On average, in easy degree of weight, patients received 1423.7 ml of liquid, at middle – 1092.6 ml at and a heavy flow - 1652.2 ml. Value for patients receiving only oral rehydration solution to patients who received only the infusion therapy and to receive both types of therapy was 1: 6,8: 2,4. Officinal drugs accounted for 62% of all appointments, often used Rehydron (47,7% and ORS (16,5%.

  16. Oral rehydration therapy of acute enteric infections

    S. M. Zacharenko

    2014-01-01

    Analysis of holding rehydration therapy in acute intestinal infections in both civilian and military care facilities showed that the civilian centers of this type of therapy was appointed by 84,5% of patients, and in the military – 50,16%. The average duration of oral rehydration therapy was 4,0 days at the easy degree of weight, at middle – 5,3 and at a heavy flow – 5,7 days. On average, in easy degree of weight, patients received 1423.7 ml of liquid, at middle – 1092.6 ml at and a heavy flo...

  17. Analysis of public oral toxicity data from REACH registrations 2008-2014.

    Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

    2016-01-01

    The European Chemicals Agency, ECHA, made available a total of 13,832 oral toxicity studies for 8,568 substances up to December 2014. 75% of studies were from the retired OECD Test Guideline 401 (11% TG 420, 11% TG 423 and 1.5% TG 425). Concordance across guidelines, evaluated by comparing LD50 values ≥ 2000 or < 2000 mg/kg body weight from chemicals tested multiple times between different guidelines, was at least 75% and for their own repetition more than 90%. In 2009, Bulgheroni et al. created a simple model for predicting acute oral toxicity using no observed adverse effect levels (NOAEL) from 28-day repeated dose toxicity studies in rats. This was reproduced here for 1,625 substances. In 2014, Taylor et al. suggested no added value of the 90-day repeated dose oral toxicity test given the availability of a low 28-day study with some constraints. We confirm that the 28-day NOAEL is predictive (albeit imperfectly) of 90-day NOAELs, however, the suggested constraints did not affect predictivity. 1,059 substances with acute oral toxicity data (268 positives, 791 negatives, all Klimisch score 1) were used for modeling: The Chemical Development Kit was used to generate 27 molecular descriptors and a similarity-informed multilayer perceptron showing 71% sensitivity and 72% specificity. Additionally, the k-nearest neighbors (KNN) algorithm indicated that similarity-based approaches alone may be poor predictors of acute oral toxicity, but can be used to inform the multilayer perceptron model, where this was the feature with highest information value. PMID:26863198

  18. Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail

    Hill, E.F.; Soares, J.H., Jr.

    1987-01-01

    The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

  19. Oral Phenytoin Toxicity Causing Sinus Arrest: A Case Report

    Thimmisetty, Ravi K.; Gorthi, Janardhana Rao

    2014-01-01

    We present a case of sinus node arrest leading to symptomatic junctional bradycardia from oral phenytoin toxicity, which is a rare presentation. Our patient had no prior cardiac history and was on phenytoin therapy for seizure disorder. Although bradycardia is more commonly associated with intravenous phenytoin and there were few case reports of bradycardia with oral phenytoin reported, the literature is limited. In this case report, we also reviewed the pathophysiology of phenytoin-induced cardiac toxicity. PMID:25343048

  20. Oral idarubicin plus cytosine arabinoside in the treatment of acute non lymphoblastic leukemia in elderly patients.

    Pagano, L; Sica, S; Marra, R; Voso, M T; Storti, S; Di Mario, A; Leone, G

    1991-01-01

    Eighteen acute nonlymphoblastic leukemia patients greater than 60 yr., 12 at diagnosis and 6 in first relapse, were treated with the association of oral Idarubicin and subcutaneous Aracytin. One patient was not evaluable. Eight out of 17 patients achieved complete remission (47%), 4 patients died in induction and 5 proved resistant to treatments. Mucocutaneous and gastrointestinal toxicity was mild. The most frequent extra-hematological complications were infections. We observed an important hepatic toxicity in 1 case. PMID:1820991

  1. A 6-Week Oral Toxicity Study of Oral Cholera Vaccine in Sprague-Dawley Rats

    Baek, Yeong-Ok; Choi, Seuk-Keun; Shin, Seo-Ho; Koo, Kyo-Hwan; Choi, Ho-Young; Cha, Seung-Bum; Li, Yong-Chun; Yoo, Hyeon-Jeong; Lee, Joo-Young; Kil, Ki-Hyun; Kim, Hak-Soo; Kang, Min-Soo; Kang, Boo-Hyun; Kim, Kap-Ho; Bae, Jin-Sook

    2012-01-01

    The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OC...

  2. Methotrexate-induced acute toxic leukoencephalopathy

    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

  3. Subchronic oral toxicity studies with α-cyclodextrin in rats

    Lina, B.A.R.; Bär, A.

    2004-01-01

    The toxicity of α-cyclodextrin (α-CD), a cyclic polymer of six α-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week st

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

    Cem Sahin; Ethem Acar; Halil Beydilli; Kadir Ugur Mert; Fatih Akin; Ibrahim Altun

    2015-01-01

    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 myocardi...

  5. Acute toxicity and laxative activity of Aloe ferox resin

    Vanessa R. L. Celestino

    2013-04-01

    Full Text Available Aloe ferox Mill., Xanthorrhoeaceae, resin is the solid residue obtained by evaporating the latex that drains from the leaves transversally cut. Aloe ferox has been used in folk medicine as anti-inflammatory, immunostimulant, anti-bacterial, anti-fungal, antitumor, laxative and to heal wounds and burns. The effects of the oral administration of A. ferox resin (10, 25, 50, 100 and 200 mg/kg were evaluated on intestinal transit in mice and its acute toxicity (5.0 g/kg in Wistar rats. The hydroxyanthracene derivatives present in the resin were expressed as aloin, identified by thin layer chromatography and quantified by spectrophotometry. The aloin (Rf 0.35 was identified and the percentage of hydroxyanthracene derivates expressed as aloin was 33.5%. A. ferox resin extract (50, 100 and 200 mg/kg increased the gastrointestinal motility at a 30 min interval at 93.5, 91.8 and 93.8%, respectively, when compared to control group (46.5%. A single oral dose of the A. ferox resin extract did not induce signs of toxicity or death. Thus, the results demonstrate that A. ferox has laxative activity and that it is nontoxic, since LD50 could not be estimated and it is possibly higher than 5.0 g/kg.

  6. Acute Toxicity of Four Organophosphorus Pesticide Products

    2012-01-01

    Acute toxicity of phoxim,acephate,isofenphos-methyl and isocarbophos on male SD rats of clean grade was carried out by gastric lavage method at room temperature of 18℃. These rats are 4 to 5 months old with body weight of 180 to 220 kg. The results indicate that the orders of the toxicity of these four pesticides on SD rats are isofenphos-methyl,isocarbophos,acephate,phoxim. We found that the median lethal concentration of phoxim in 24 h,48 h,72 h and 96 h is 3. 892 g /kg,3. 051 g /kg,2. 618 g /kg and 2. 458 g /kg respectively; the median lethal concentration of isofenphos-methyl in 24 h,48 h,72 h and 96 h is 0. 015 g /kg,0. 013g /kg,0. 012g /kg and 0. 011 g /kg respectively; the median lethal concentration of isocarbophos in 24 h,48 h,72 h and 96 h is 0. 049 g /kg,0. 046 g /kg,0. 043 g /kg,0. 041 g /kg respectively; and the median lethal concentration of acephate in 24 h,48 h,72 h and 96 h is 0. 137 g /kg,0. 113 g /kg,0. 100 g /kg,0. 085 g /kg respectively. Finally,we evaluated the characteristics of toxicity effect and safe concentration of these pesticides to SD rats.

  7. Acute and subchronic toxicity of hydroxylammonium nitrate in Wistar rats

    An Hui; Liu Jinyi; Yang Lujun; Liu Shengxue; Zhou Yanhong; Yang Huan; Jia Qingjun; Cui Zhihong; Cao Jia

    2008-01-01

    Hydroxylammonium nitrate (HAN) is a major constituent in a class of liquid monopropellants and is extensively used in nuclear industry and space propulsion. Previous toxicological studies have focused on oral, inhalation and dermal routes of exposure to HAN-based propellant blends. In this study, acute and subchronic toxicity of HAN in Wistar rats by intraperitoneal injections were evaluated. In this acute study, doses of HAN at 115, 125, 135, 147, 160 or 174 mg/kg were administered. No adverse effects were observed during a 14-day period and at gross histopathological examination. In the subchronic study, HAN at 7, 14 or 28 mg/kg were administered for 13 weeks. The treatment with HAN caused significant changes in the weight of spleen, in the level of hematological parameters, total bilirubin, direct bilirubin, uric acid and carbondioxidecombining power and histopathological damages of the lung, liver, spleen and kidney. Overall, the study suggests that 13-week HAN treatment caused abnormal hematological changes and tissue lesions, and the risk of toxicity to mammals is not negligible.

  8. Intravenous Voriconazole after Toxic Oral Administration▿

    Alffenaar, J. W. C.; Van Assen, S.; de Monchy, J G R; Uges, D. R. A.; Kosterink, J. G. W.; VAN DER WERF, T S

    2009-01-01

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate liver enzyme abnormalities, and therefore, oral administration of voriconazole may have a hepatotoxicity profile different from that of intravenous (i.v.) administration. Intravenously administered vo...

  9. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    2012-07-23

    ... testing is required by multiple agencies, can involve large numbers of animals, and can result in... dermal exposures; in vivo dermal and oral toxicity testing; and test method validation. Each nomination... HUMAN SERVICES Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity...

  10. Acute and sub-acute toxicity studies of aqueous and methanol extracts of Nelsonia campestris in rats

    Janet Mobolaji Olaniyan; Hadiza Lami Muhammad; Hussaini Anthony Makun; Musa Bola Busari; Abubakar Siddique Abdullah

    2016-01-01

    Objective: To evaluate the acute and sub-acute toxicity of aqueous and methanol ex-tracts of Nelsonia campestris (N. campestris) in rats. Methods: Acute oral toxicity study of aqueous and methanol extracts was carried out by administration of 10, 100, 1 000, 1 600, 2 900 and 5 000 mg/kg body weight of N. campestris extracts to rats in the respective groups. Sub-acute toxicity study was conducted by oral administration of the extracts at daily doses of 100, 300 and 600 mg/kg body weight to another group of rats for 28 days, while rats in the control group received 0.5 mL of normal saline. Results: The LD50 of the N. campestris extracts in rats was determined to be greater than 5 000 mg/kg body weight. There was no significant difference (P>0.05) between the test groups administered with aqueous and methanol extracts in relation to the control group for serum electrolytes (Na+, K+, Cl−, HCO3−), serum albumin, total and conjugated bili-rubin. Similarly, mean organ-to-body weight ratio and all haematological parameters (white blood cell, red blood cell, mean cell volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, packed cell volume) evaluated were not significantly different (P > 0.05) from the control. There was a significant increase (P Conclusions: Intake of high doses of this plant extracts may exhibit mild organ toxicity.

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

    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. PMID:25345248

  12. The value of acute toxicity testing of pharmaceuticals for estimation of human response.

    Barle, Ester Lovšin; Looser, Roland; Cerne, Manica; Bechter, Rudolf

    2012-04-01

    The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID:22306828

  13. [Acute toxicity testing (LD50) of Chinese mineral drugs].

    Yue, W; Liu, W H; Wang, L F; Fu, S X; Li, Y S; Kong, Z K; Tang, Z X; Chen, Z L

    1989-02-01

    Acute toxicity and LD50 of 62 mineral drugs were determined by ig, ip or iv in mice, in order to provide some guidelines for safety in clinical use, as well as for pharmacological and toxicological studies. In the present investigation, the difference in the acute toxicity and LD50 between raw drugs and medicines prepared by roasting is explained. PMID:2506896

  14. Acute Toxicity of Justicia gendarussa Burm. Leaves

    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.

  15. Study on alternative methods for the acute oral toxicity in detection of chemicals%急性经口毒性替代方法在化学品检验中的应用研究

    谭剑斌; 赵敏; 杨杏芬; 周轶琳; 陈壁锋; 陈瑞仪; 黄建康

    2011-01-01

    ,the concordance rates of FDP,ATC and UDP was 91.7%(11/12),75.0%(9/12) and 83.0%(10/12),respectively.The number of animals required in three alternative methods was significantly lower than that in traditional test (P<0.05),but the time required in three alternative methods was significantly higher than that in traditional test (P<0.05 ).Conclusions High consistency and correlation were found between each alternative method and LD50 test.FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.

  16. Phenytoin toxicity presenting as acute meningo-encephalitis in children

    Vijay Gupta

    2011-01-01

    Full Text Available Phenytoin can produce significant dose-related toxicity because of its zero order pharmacokinetics and is an important issue in pediatric emergency medicine. It is important to differentiate phenytoin toxicity manifesting with symptoms like fever, vomiting, seizures, ataxia masquerading as acute meningo-encephalitic illness, more so at centers where facilities to measure serum phenytoin levels are not available. Here we describe two children with phenytoin toxicity, presenting to the emergency department with features suggestive of acute meningo-encephalitis.

  17. ACUTE AND SUBACUTE TOXICITY STUDY ON SPERMATOGENIC SIDDHA DRUG ‘ISAPPUKOL CHOORANAM’ (IC

    S. Thillaivanan*, K. Kanagavalli , P. Sathiyarajeswaran and P. Parthiban

    2013-11-01

    Full Text Available Herbal medicines have been broadly used in developed countries hence they are natural and comparatively safe. They contain plant materials as their pharmacologically active components. Infertility is one of the most extremely tragic all over the world. Despite recent advances in the treatment of male infertility, the problem has not been satisfactorily tackled. The male infertility is mainly due to an inadequate number of spermatozoa in the semen, the failure of the spermatozoa to move with sufficient vigor towards their goal. Aim of the study is to evaluate the acute and sub-acute toxicity of the spermatogenic siddha drug Isappukol Chooranam (IC (siddha drug.For acute studies, different doses of IC were administered orally to rats once daily for one week. Forsub-acute studies, different doses of IC were administered orally to rats once daily for 28 days in various doses at 50,100,200 mg/kg of body weight. Detailed hematological, biochemical, necropsy and Histopathological evaluation of organs was performed for all animals. Histopathological analysis revealed that Spleen, Testes, Pancreas, Lung, Liver, Brain, Heart, Stomach, Intestine, Bone, Ovary, and Kidney tissues of treated groups did not show any signs of toxicity. No impairment in hepatic, renal, haemopoietic functions were observed throughout the study. No mortality was observed up to 200 mg/kg of body weight in acute and sub-acute toxicity studies.

  18. Phytochemical and acute toxicity studies of ethanol extract from Pedada (Sonneratia caseolaris fruit flour (PFF

    Jariyah Jariyah

    2015-01-01

    Full Text Available Studies on the phytochemical and acute toxicity of pedada fruit flour (PFF were carried out. In acute toxicity test, oral administration of the extract to Swiss albino mice at four levels dose, i.e. 0, 10.50; 15.75 and 21.00 g/kg body weight.  Phytochemical analysis of the ethanol extract of PFF showed the presence of saponins, sapogenins, terpenoids, flavonoids, tannins,  polyphenols. Phytochemicals such as alkaloids were not detected. The results of acute toxicity (LD50 showed that the ethanol extract of PFF in mice was found more than 21.00 g/kg body weight. It could be concluded that the PFF belongs to relatively less dangerous category ‘non toxic’ and ‘safe’ for food products.

  19. Acute toxicity study of the oil from Azadirachta indica seed (neem oil).

    Gandhi, M; Lal, R; Sankaranarayanan, A; Banerjee, C K; Sharma, P L

    1988-01-01

    The seed oil of Azadirachta indica (neem oil) is well known for its medicinal properties in the indigenous Indian system of medicine. Its acute toxicity was documented in rats and rabbits by the oral route. Dose-related pharmacotoxic symptoms were noted along with a number of biochemical and histopathological indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24 ml/kg in rabbits. Prior to death, animals of both species exhibited comparable pharmacotoxic symptoms in order and severity, with lungs and central nervous system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was tested in the same manner to document the degree to which the physical characteristics of an oil could contribute to the oral toxicity of neem oil. PMID:3419203

  20. Evaluation of the acute and sub acute toxicity ofAnnona senegalensis root bark extracts

    Theophine C Okoye; Peter A Akah; Adaobi C Ezike; Maureen O Okoye; Collins A Onyeto; Frankline Ndukwu; Ejike Ohaegbulam; Lovelyn Ikele

    2012-01-01

    ABSTRACT Objective:To investigate the safety profile ofAnnona senegalensis (A. senegalensis).Methods:Dried powdered root-bark of A. senegalensis was prepared by Sohxlet extraction using methanol-methylene chloride (1:1) solution and concentrated to obtain the methanol-methylene chloride extract (MME).MME was fractionated to obtain then-hexane (HF), ethylacetate (EF) and methanol (MF) fractions. Acute toxicity (LD50) test was performed withMME, HF, EF andMF in mice by oral route. The sub acute toxicity studies were performed in rats after14 days ofMME administration while haematological and biochemical parameters were monitored.Results:Medium lethal (LD50) values of1 296, 3 808, 1 265 and 2 154mg/kg were obtained for theMME, MF, HF andEF, respectively. The sub-acute toxicity studies indicated a significant (P<0.05) increase in the body weight of both the treated rats and the control. The haematological tests indicated no change in the packed cell volume values but a significant (P<0.05) increase in the totalWBC count at100and 400 mg/kg doses. The differential analysis showed a decrease in the nutrophils and a non-significant increase in the lymphocyte counts. The liver transaminase enzymes, alanin transaminase and aspartate transaminase showed no significant increase compared to the control. Histopathological examination of the liver sections also indicted no obvious signs of hepatotoxicity except with the400 mg/kg dose that showed degeneration and necrosis of the hepatocytes.Conclusions:These results indicated that the root bark extracts ofA. Senegalensis are safe at the lower doses tested, and calls for caution in use at higher doses in treatment.

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

    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.

  2. Experimental oral lead toxicity in young dogs

    Stowe, H.D.; Goyer, R.A.; Krigman, M.M.; Wilson, M.; Cates, M.

    1973-02-01

    Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia, and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.

  3. ACUTE AND CHRONIC TOXICITY OF CHLORDANE TO FISH AND INVERTEBRATES

    The acute and chronic toxicity of technical chlordane to bluegill (Lepomis macrochirus), fathead minnow (Pimephales promelas), brook trout (Salvelinus fontinalis), Daphnia magna, Hyallela azteca, and Chironomus No. 51 were determined with flow-through conditions. The purpose was ...

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

    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...

  5. A New Method for Determining Acute Toxicity in Animal Models

    Chinedu, Enegide; Arome, David; Ameh, Fidelis Solomon

    2013-01-01

    Background: The intake of pharmacological substances by man has solely increased and this may be in the form of food, medicines and beverages, other industrial and household products. These substances are capable of eliciting chronic and acute toxicity, which may be mild or severe, depending upon their nature. Acute toxicity is defined as the unwanted effect(s) that occurs either immediately or at a short time interval after a single or multiple administration of such substance within 24 hour...

  6. Subacute (90 Days) Oral Toxicity Studies of Kombucha Tea

    2000-01-01

    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.

  7. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    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 CO2 and by observing the disappearance of test substance with gas chromatography. Additional BOD5 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

  8. Acute and subchronic toxicity study of the water extract from root of Citrus aurantifolia (Christm. et Panz.) Swingle in rats

    Kanjana Jaijoy; Nadthaganya Suwanlikhid; Anongnad Ngamjariyawat; Amornnat Thuppia; Nirush Lertprasertsuke; Umarat Srisawat; Siharat Chunlaratthanaphorn

    2007-01-01

    Acute and subchronic toxicities of the water extract from the roots of Citrus aurantifolia were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 male, 5 female) did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 300, 600 and 1,200 mg/kg body weight for 90 days (10 ma...

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

    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. Assessing delayed and acute toxicity of five formulated fungicides to Osmia lignaria Say and Apis mellifera

    Ladurner, Edith; Bosch, Jordi; P. Kemp, William; Maini, Stefano

    2005-01-01

    International audience The delayed and acute toxicity of benomyl (Benlate®), captan (Captan 50WP), iprodione (Rovral®), propiconazole (OrbitTM), and neem oil (Trilogy®) to two crop pollinators, A. mellifera and O. lignaria, was evaluated. Survival after contact and oral single exposure to high doses of the pesticides was compared to survival of controls with the dosing vehicle. LD50 values at 24, 48 and 72 h from exposure were determined. Contact and oral exposure to benomyl and iprodione ...

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

    Luciano Rezende Vilela; Lindisley Ferreira Gomides; Bruna Araújo David; Maísa Mota Antunes; Ariane Barros Diniz; Fabrício de Araújo Moreira; Gustavo Batista Menezes

    2015-01-01

    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 hyd...

  12. EURL ECVAM Recommendation on the Zebrafish Embryo Acute Toxicity Test Method (ZFET) for Acute Aquatic Toxicity Testing

    HALDER MARIA ELISABETH; GRIESINGER Claudius; AMCOFF SVEN PATRIK; ZUANG Valerie; Whelan, Maurice

    2014-01-01

    Acute fish toxicity testing is an important component of the environmental hazard assessment of chemicals. Since many years, (zebra-)fish embryo-based methods have been proposed as alternatives to the acute fish toxicity test carried out with juvenile or adult fish. On behalf of the Organisation for Economic Cooperation and Development (OECD), the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) coordinated during 2008-2012 the validation of the zebrafish em...

  13. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    Pels, Elżbieta

    2012-01-01

    Aim of the study Oral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy. Material and methods The clinical examination included 78 children aged 2-18 with ALL. The clinica...

  14. Single-dose oral toxicity of fermented rice extracts (FREs): a 14-day observation.

    Choi, Jae-Suk; Kim, Joo-Wan; Kim, Ki-Young; Ku, Sae-Kwang; Sohn, Jae Hak

    2014-01-01

    The aim of present research was to determine the acute oral toxicity of fermented rice extracts (FREs), in female and male ICR mice. To investigate the toxicity and identify target organs, FREs were orally administered once to male and female ICR mice at doses of 0 (vehicle control), 500, 1000, or 2000 mg/kg body weight (BW). Effects on mortality, BW, and clinical signs were monitored over 14 days, including changes in the weights and histopathological characteristics of 14 organs, as described in the Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). No treatment-related mortality was observed during the 14-day observation period in either gender. In addition, no FRE-related change was observed in BW or organ weight (OW), clinical indicators, or histopathological findings in this study. Our results suggest that the FRE is non-toxic in mice and is therefore likely to be safe for clinical use. The approximate LD and LD50 in mice after single oral dose of FRE are greater than 2000 mg/kg in female and male ICR mice. Additionally, no specific target organ or negative clinical indicator was detected in this study. PMID:24374435

  15. Intravenous Versus Oral Outpatient Antibiotic Therapy for Pediatric Acute Osteomyelitis

    Liu, Raymond W.; Abaza, Hadeel; Mehta, Priyesh; Bauer, Jennifer; Cooperman, Daniel R.; Gilmore, Allison

    2013-01-01

    The optimal route (oral versus intravenous) of antibiotic administration for pediatric acute osteomyelitis is not well established. Seventy-eight children from our university hospital and 17 children at our county hospital were treated for acute osteomyelitis. The rates of intravenous antibiotics upon discharge were 95% versus 65% (P=0.002), respectively. The recurrence rate and line complication rates were 10% and 24% at the university hospital, compared to 0% (P=0.34) and 6% (P=0.29) at the...

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

    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. Subacute(90Days) Oral Toxicity Studies of Kombucha Tea

    R.VIJAYARAGHAVAN; MANINDERSINGH; 等

    2000-01-01

    Kombucha tes(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 coutries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments,viz.,intestinal disorders,arthritis,ageing and stiumulation of immunological system.Though KT is used in several parts of the world its eneficial 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 goups of rats were maintained:(a) control group given tap water orally,(b) KT given 2ml/kg orally,(c)plain tea(PT) given 2ml/kg orally,(d)KT given in drinking water,1%(v/v)and (e)PT given indrinking 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 progrssive body weight change.The organ to body weight ration and histologuical 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 day showed no toxic effects.

  18. Preclinical studies on safety of fullerene upon acute oral administration and evaluation for no mutagenesis

    Fullerenes characterized as an antioxidant are believed to reduce various reactive chemical species, such as free radicals, and their characteristic features have been disclosed to furnish many useful medical technologies. Despite the numerous applications for the biological efficacy of fullerenes, less is known about the toxicity of fullerenes in mammals. Hence, the protocol was designed to determine the acute oral median lethal dose and evaluate the acute toxicity of fullerenes when administrated as a single dose to Sprague-Dawley rats. In an acute toxicity test, fullerenes were administered once orally to a single group of male and female at a dose level of 2000 mg/kg. No deaths were observed and the body weights in both sexes of 2000 mg/kg group increased in a similar pattern to the control group. Genotoxicity of fullerenes was also assessed in a bacterial reverse mutation assay (Ames test) and the chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. Although structural chromosomal aberrations were induced at up to 5000 μg/mL, there was no significant increase in the frequency of chromosomal aberrations at any dose level regardless of presence of S9. Fullerenes did not cause genetic damage in Salmonella typhimurium TA100, TA1535, TA98 and TA1537 and Escherichia coli WP2uvrA/pKM101. These results indicate that fullerenes are not of high toxicological significance

  19. Review of Quantitative Structure - Activity Relationships for Acute Mammalian Toxicity

    Iglika Lessigiarska

    2006-12-01

    Full Text Available This paper reviews Quantitative Structure-Activity Relationship (QSAR models for acute mammalian toxicity published in the last decade. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate system for predicting acute toxicity to mammals. On the basis of the review, the following conclusions can be made: i a relatively small number of models for in vivo toxicity are published in the literature. This is due to the nature of the endpoint - acute systemic toxicity is usually related to whole body phenomena and therefore is very complex. The complexity of the mechanisms involved leads to difficulties in the QSAR modelling; ii most QSAR models identify hydrophobicity as a parameter of high importance for the modelled toxicity. In addition, many models indicate the role of the electronic and steric effects; iii most of the literature-based models are restricted to single chemical classes. Models based on more heterogeneous data sets are those incorporated in expert systems. In general, the QSAR models for mammalian toxicity identified in this review are considered useful for investigating the mechanisms of toxicity of defined chemical classes. However, for predictive purposes in the regulatory assessment of chemicals most of the models require additional information to satisfy internationally agreed validation principles. In addition, the development of new models covering larger chemical domains would be useful for the regulatory assessment of chemicals.

  20. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  1. [Synthesis, structures, and acute toxicity of gossypol nonsymmetrical aldehyde derivatives].

    Tiliabaev, K Z; Kamaev, F G; Vypova, N L; Iuldashev, A M; Ibragimov, B T; Talipov, S A

    2010-01-01

    Nonsymmetrical aldehyde derivatives of gossypol, a yellow polyphenolic pigment of cottonseed, were synthesized by reactions with ammonia, aniline, 4-aminoantipyrine, and barbituric acid. Their structures were determined by UV spectrophotometry and IR and (1)H NMR spectroscopy methods. Their acute toxicities in white mice were compared with those of gossypol and the corresponding symmetrical analogues. It was demonstrated that in general, the fewer free aldehyde groups that contained the gossypol derivative, the lower its acute toxicity. Only in the case of a nonsymmetrical gossypol derivative bearing a 4-aminoantipyrine residue did we observe a deviation from the above correlation: its symmetrical counterpart was even more toxic, but still less toxic than gossypol. PMID:20644599

  2. ACUTE TOXICITY OF LEAD NITRATE ON FRESHWATER CRAB BARYTELPHUSA GUERINI

    DUBE, KAUSHAL V

    2012-01-01

    Industrial effluents contributing to aquatic pollution contain vast array of toxic substances including heavy metals.  Indiscriminate discharge of these wastes alters the quality of water and cause hazards to aquatic fauna including important members of food chain of man. Hence, in present investigation the freshwater crab, Barytelphusa guerini was exposed to acute toxicity of lead nitrate for 0, 24, 48, 72 and 96 hours exposure. The percentage mortality of crab was studied and the LC50 deter...

  3. Acute and subacute toxicity of 18F-FDG

    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 18F-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 18F-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 18F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

  4. Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

    Costa-Silva, J H; Lima, C R; Silva, E J R; Araújo, A V; Fraga, M C C A; Ribeiro E Ribeiro, A; Arruda, A C; Lafayette, S S L; Wanderley, A G

    2008-03-28

    Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity. PMID:18281172

  5. Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses.

    Pinto, Flávia Cristina Morone; De-Oliveira, Ana Cecília A X; De-Carvalho, Rosangela R; Gomes-Carneiro, Maria Regina; Coelho, Deise R; Lima, Salvador Vilar C; Paumgartten, Francisco José R; Aguiar, José Lamartine A

    2016-02-10

    The acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of BC were studied. Cytotoxicity of BC was evaluated in cultured C3A hepatoma cells (HepG2/C3A) using a lactate dehydrogenase (LDH) activity assay. Acute toxicity was tested in adults Wistar rats treated with a single dose of BC. The genotoxicity of BC was evaluated in vivo by the micronucleus assay. BC (0.33-170 μg/mL) added to C3A cell culture medium caused no elevation in LDH release over the background level recorded in untreated cell wells. The treatment with the BC in a single oral dose (2000 mg/kg body weight) caused no deaths or signs of toxicity. BC attenuated CP-induced and inhibition the incidence of MNPCE (female: 46.94%; male: 22.7%) and increased the ratio of PCE/NCE (female: 46.10%; male: 35.25%). There was no alteration in the LDH release in the wells where C3A cells were treated with increasing concentrations of BC compared to the wells where the cells received the cell culture medium only (background of approximately 20% cell death), indicated that in the dose range tested BC was not cytotoxic. BC was not cytotoxic, genotoxic or acutely toxic. BC attenuated CP-induced genotoxic and myelotoxic effects. PMID:26686163

  6. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    2010-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... minimize the need for animal testing, the Agency encourages the review of existing acute toxicity... need for further animal testing. (ii) Limit test. When data on structurally related chemicals...

  7. Acute aqueous toxicities of diesel-biodiesel blends

    Hollebone, B.P.; Ho, N.; Landriault, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science and Technology Division, Science and Technology Branch, Environmental Science and Technology Centre; Harrison, S. [Science Applications International Corp., SAIC Canada, Ottawa, ON (Canada); Doe, K.; Jackman, P. [Environment Canada, Moncton, NB (Canada). Toxicology Laboratory, Environmental Science Centre

    2008-07-01

    The renewed interest in biodiesels as a new transportation fuel was discussed. Although there are several advantages to using biodiesels, their environmental behaviours and effects need to be evaluated along with the risks associated with their use, such as accidental releases of these biodiesels to the environment. The wide variability of biodiesels may result in different toxicological impacts, depending on the fuel feedstock. This study evaluated the aqueous effects of biodiesels from several commonly available feedstocks and their blends with petroleum diesel. Since most of the commercial uses of these products are currently focused on road-use, this study focused on the effects of these fuels in fresh-water. Biodiesels derived from soy, canola and waste restaurant oil feedstocks were used in the study. The acute toxicities of these biodiesels and biodiesel/petroleum diesel fuel blends were reported for 3 test species used by Environment Canada for toxicological evaluation, notably rainbow trout, the water flea, and a luminescent bacterium. The correlations between acute toxicity, water accommodated fractions (WAF) concentrations and fuel property data were examined. The study revealed that biodiesel is significantly less acutely toxic than petroleum diesels in potential ecological impacts. However, the biodiesel-diesel blends were found to be more acutely toxic than a linear dilution model predicts. 11 refs., 6 tabs., 3 figs.

  8. Studies on acute toxicity and mutagenicity of 60Co irradiated pollens

    The acute toxicity test showed that the oral LD50 values were >21500 mg/kg for male and female mice, indicating that irradiated pollens belong to low toxicity grade or practically non-toxic. Mutagenicity were studied in three short-term tests. Ames test showed that irradiated pollens did not induce mutation towards strains TA99, TA97, TA100 and TA102. Micronucleus test in the bone marrow cells indicated that the percentage of polychromatic erythrocytes with micronuclei in exposed groups had no significant difference in comparison with the controlled ones. Chromosomal test for reproduction cells showed that the increase of chromosomal aberration rate was not observed. All the above results suggest that irradiated pollens are safe for human consumption

  9. Management of acute stroke in patients taking novel oral anticoagulants

    Hankey, Graeme J; Norrving, Bo; Hacke, Werner; Steiner, Thorsten

    2014-01-01

    Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offer...

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

    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.

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

    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

  12. Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

    Cho, MyoungLae; Shin, Gi-Hae; Kim, Jae-Min; Lee, Jin-Ha; Park, Sun-Ok; Lee, Sang-Jong; Shin, HyunMu; Lee, Boo-Yong; Kang, Il-Jun; Lee, Ok-Hwan

    2016-06-01

    The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats. PMID:26925497

  13. In vitro examination of oral tissue conditioners potential toxicity

    Krunić Nebojša

    2011-01-01

    Full Text Available The oral tissue conditioners are applied temporarily to the gingival surface of a denture for the purpose of reconditioning the abused denture supporting tissues, allowing them to return to a normal, healthy state. According to chemical composition they can be classified into methacrylic and silicon conditioners. The objective of this research was to examine the potential toxicity of one, seven and thirty day extracts of different concentrations. Different effective concentrations (5, 12.5, 25 and 50% of two silicone and four methacrylic conditioners extracts were used after extraction period of one, seven and thirty days. Amount of toxic substances and dynamics of their release were monitored by high-pressure liquid chromatography (HPLC. HPLC analysis could not be applied to the silicone conditioners because they consist of polymeric and inorganic 19 substances. Evaluation of cell proliferation, as cytotoxic parameters, was done by Mosmann’s MTT assay based on reduction of yellow tetrazole (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide - MTT to purple formazan by mitochondrial succinate dehydrogenase of metabolic active cells. With increasing of extraction period, the amount of released potential toxic substances increased. The cytotoxicity of tested materials significantly increased with extract concentration increase and duration of extraction period. To improve the biological characteristics of mobile dentures relined by soft materials, soaking in water the day before insertion into patient’s mouth was recommended. Silicone conditioners showed less cytotoxicity compared to the methacrylic conditioners, so they are more appropriate for daily dental practice.

  14. Acute and sub-chronic toxicity studies of an aqueous stem bark extract of Sclerocarya birrea using a rat model

    Tariro Mawoza; Dexter Tagwireyi; Charles Nhachi

    2016-01-01

    Background: Sclerocarya birrea, a plant that is commonly available in many communities, is used as a source of food and for ethnomedicinal and cultural practices. Stem-bark toxicity studies for the plant are however lacking. This study was therefore conducted in an effort to determine its toxic effects using a rat model. Methods: Acute toxicity was performed using a single oral administration of 50, 100, 200, 400, 800, 1000 and 2000mg/kg body weight of S. birrea to determine the lethal dose. ...

  15. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    Arbabi Bidgoli S

    2011-04-01

    Full Text Available M Korani1, SM Rezayat1,2,4, K Gilani3, S Arbabi Bidgoli4, S Adeli11Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences; 2Department of Nanotechnology, Faculty of Advanced Sciences and Technology in Medicine, Tehran University of Medical Sciences; 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences; 4Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS, Tehran, IranAbstract: Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 µg/mL in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 µg/mL in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater

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

    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

  17. ACUTE DERMAL TOXICITY STUDIES OF TROISTM IN NEWZEALAND WHITE RABBITS

    Anurag Payasi

    2010-06-01

    Full Text Available The study was performed to assess the acute dermal toxicity of TroisTM in Newzealand white rabbit. Test substance was applied as such to the shaven skin of group of rabbits at the dose of 2000 mg/Kg body weight. Control group of animals were similarly treated but only with base. Following dosing up to 14 days the rabbits were observed for mortality and clinical sign of toxicity. No visible signs of toxicity after treatment were observed on the animals of both control and treated animals up to 14 days. Various haematological and biochemical parameters were evaluated and found to be in the normal limit, which indicates that no sign of toxicity in NewZealand white rabbits after 14 days treatment in respect to control group, proving safety of TroisTM in topical application.

  18. Acute toxicity of 50 metals to Daphnia magna.

    Okamoto, Akira; Yamamuro, Masumi; Tatarazako, Norihisa

    2015-07-01

    Metals are essential for human life and physiological functions but may sometimes cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were Mo) were > 100,000 µg l(-1) ; and. 7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd adhered to the body of D. magna and physically retarded the movement of D. magna. These metals formed hydroxides after adjusting the pH. Therefore, here, we distinguished this physical effect from the physiological toxic effect. The acute toxicity results of 40 elements obtained in this study were not correlated with electronegativity. Similarly, the acute toxicity results of metals including the rare metals were also not correlated with first ionization energy, atomic weight, atomic number, covalent radius, atomic radius or ionic radius. PMID:25382633

  19. Acute and subacute toxicity of 18F-FDG

    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 18F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18F-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)

  20. Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    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. PMID:25999668

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

    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.

  2. Antimicrobial activity and acute and chronic toxicity of the essential oil of Lippia origanoides

    Viviane A. Andrade

    2014-12-01

    Full Text Available Currently, there is a growing interest in medicinal plants, because of an increased demand for alternate therapies. In this study, the antimicrobial activity and toxicity of the essential oil of Lippia origanoides (L. origanoides were investigated. The essential oil of L. origanoides was extracted by steam-dragging distillation and its constituents were identified by chromatography coupled with mass spectrometry. Among the 15 compounds identified, the most abundant were carvacrol (29.00%, o-cymene (25.57%, and thymol methyl ether (11.50%. The essential oil was studied in antimicrobial assays to determine the MIC and MBC. The results indicated that a concentration of 120μL/mL of oil was sufficient to inhibit the growth of the following microorganisms: Escherichia coli (ATCC 25922, Staphylococcus aureus (ATCC 25923 and Salmonella cholerasuis (ATCC 10708. Acute and chronic toxic effects of orally administered oil were investigated in Wistar rats by using standard methods. Doses of 30, 60 and 120mg/kg of the essential oil did not induce significant changes in weight, behavior or hematological and biochemical parameters in the animals. There were no signs of any histopathological changes to the liver, kidneys or heart of the treated rats, suggesting that Lippia origanoides oil is non-toxic after oral administration in acute or chronic toxicity studies. The results obtained in this study show that the essential oil of L. origanoides has a high safety margin, with no detectable toxic effects in rats treated with doses to 120mg/kg. In addition, L. origanoides oil demonstrated potent antimicrobial activity against S. aureus, E. coli and S. cholerasuis. Based on these findings, this essential oil may have practical application as a veterinary antimicrobial.

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

    Uranium hexafluoride (UF6) released into the atmosphere will react rapidly with moisture in the air to form the hydrolysis products uranyl fluoride (UO2F2) and hydrogen fluoride (HF). Uranium compounds such as UF6 and UO2F2 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 UF6, UO2F2, and HF. 4 refs., 2 figs., 5 tabs

  4. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats. PMID:24892475

  5. Severe hypotension and hypothermia caused by acute ethanol toxicity

    Wilson, E; W. S. Waring

    2007-01-01

    This article reports the time course and clinical features of acute ethanol poisoning in an elderly man who had previously abstained from alcohol. Several hours after ingestion, severe hypotension and hypothermia developed, and the consciousness level was reduced. Supportive measures were sufficient to allow the patient's blood pressure and temperature to recover by 24 h post ingestion. The clinical manifestations of ethanol toxicity are often confounded by coexistent drug ingestion and varia...

  6. Evaluation of acute toxicity of babassu mesocarp in mice

    Elizabeth S. B. Barroqueiro; Fernanda S. B. Barroqueiro; Mayara T. Pinheiro; Márcia C. G. Maciel; Priscila S. Barcellos; Silva, Lucilene A.; Adelson de S. Lopes; Flávia R.F. Nascimento; Rosane N. M. Guerra

    2011-01-01

    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 gluco...

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

    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.

  8. Acute toxicity and metabolomics analysis of hypocholesterolemic effect of Mentha piperita aqueous extract in Wistar rats

    Nor Zaini Johari

    2015-01-01

    Full Text Available Summary. The oral acute toxicity of the aqueous peppermint extract (APE was assessed and the bio and/or chemo markers for hypocholesterolemic activity of APE were identified through metabolomics approach. No mortality resulted from the present oral acute toxicity study in which the histological changes observed in the selected organs and the biochemical deviation of blood compared to the normal range level were minimal. This study also explored the effect of 290 mg-1 kg body weight of APE against 5% cholesterol-enriched diet within 14 days treatment. Whereby after the treatment, there were reductions exhibited in plasma total cholesterol (44.32%, LDL-cholesterol (69.19% and total triglycerides (55.77%. 1H NMR-metabolomics approach was, employed for better sensitivity and accuracy in evaluating the  potential plasma biomarkers of hyper-and hypo-cholesterolemic properties. β-Hydroxybutarate and α-D-glucose have been identified as the possible hypercholesterolemic markers, whereas taurine, betaine, alanine, glycine and L-leucine were suggested to be the hypocholesterolemic markers of APE.  Industrial relevance. Due to various reports on the side effects of conventional drug-lowering cholesterol available in the market, aqueous peppermint extract at its recommended consumption dosage has been investigated over its toxicity of oral consumption and its efficacy against elevation of cholesterol level in blood. The evaluation of hypocholesterolemic activity of aqueous peppermint extract (APE, from which the potential biomarkers could be established, might be useful in the  development of new anti-cholesterol drug and also for quality control of peppermint-based products. Keywords. Mentha piperita; peppermint; hypercholesterolemia; metabolomics; 1H NMR; multivariate data analysis

  9. Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

    Wik, Anna; Dave, Göran

    2006-09-01

    Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment. PMID:16466775

  10. Evaluation of acute toxicity potential of water hyacinth leaves.

    Wu, Wenbiao; Guo, Xiaoguang; Huang, Mingliang

    2014-06-01

    Although higher protein yield per hectare of water hyacinth than that of soy, high protein content of its leaves and good essential amino acid pattern have been proven, its dietary toxicity for human or animal consumption has not yet been evaluated. Therefore, the acute toxicity of water hyacinth leaves has been evaluated by an animal feeding test. The concentrations of common toxic metals including cadmium, lead, platinum, palladium, tin, mercury, barium, silver, stibium and aluminum in the water hyacinth leaf powder (WHLP) used for the animal feeding test were within their maximum limits in food additives as reported by the World Health Organization. The median lethal dose (LD50) of WHLP was more than 16 g kg(-1) body weight. In the study, after feeding for 7 and 28 days, the body weight of all the mice increased. The results of hematological analysis, clinical biochemical analysis, histopathological evaluation, general dissection or investigations of internal organs, appearance and behavior observations did not indicate any adverse effects from the diet containing WHLP. It is therefore concluded that water hyacinth leaves are not acutely toxic. PMID:22933551

  11. Acute Toxicity and Efficacy of Psidium guajava Leaves Water Extract on Salmonella Typhi Infected Wistar Rats

    E.U. Etuk

    2003-01-01

    Full Text Available The acute toxicity and efficacy of Psidium guajava leaves water extract on Salmonella typhi infected wistar rats had been studied. Oral administration of 10–50 mg/100 g of the extract showed no significant harmful effect in the animals after 72 h. The administration of 10-30 mg/100 g of the extract 12 h through the same route to rats infected with Salmonella typhi produced a recovery within seven days. The Salmonella infection equally responded to chloramphenicol, a conventional antibiotic used in the treatment of this infection. These results suggested that the water extract of Psidium guajava leave was non toxic at the tested doses and effective against Salmonella infection in wistar rats.

  12. Acute and delayed toxicities of total body irradiation

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  13. Acute and delayed toxicities of total body irradiation

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation

  14. Cholinesterase inhibition and alterations of hepatic metabolism by oral acute and repeated chlorpyrifos administration to mice.

    Cometa, Maria Francesca; Buratti, Franca Maria; Fortuna, Stefano; Lorenzini, Paola; Volpe, Maria Teresa; Parisi, Laura; Testai, Emanuela; Meneguz, Annarita

    2007-05-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphorus insecticide bioactivated in vivo to chlorpyrifos-oxon (CPFO), a very potent anticholinesterase. A great majority of available animal studies on CPF and CPFO toxicity are performed in rats. The use of mice in developmental neurobehavioural studies and the availability of transgenic mice warrant a better characterization of CPF-induced toxicity in this species. CD1 mice were exposed to a broad range of acute (12.5-100.0mg/kg) and subacute (1.56-25mg/kg/day from 5 to 30 days) CPF oral doses. Functional and biochemical parameters such as brain and serum cholinesterase (ChE) and liver xenobiotic metabolizing system, including the biotransformation of CPF itself, have been studied and the no observed effect levels (NOELs) identified. Mice seem to be more susceptible than rats at least to acute CPF treatment (oral LD(50) 4.5-fold lower). The species-related differences were not so evident after repeated exposures. In mice a good correlation was observed between brain ChE inhibition and classical cholinergic signs of toxicity. After CPF-repeated treatment, mice seemed to develop some tolerance to CPF-induced effects, which could not be attributed to an alteration of P450-mediated CPF hepatic metabolism. CPF-induced effects on hepatic microsomal carboxylesterase (CE) activity and reduced glutathione (GSH) levels observed at an early stage of treatment and then recovered after 30 days, suggest that the detoxifying mechanisms are actively involved in the protection of CPF-induced effects and possibly in the induction of tolerance in long term exposure. The mouse could be considered a suitable experimental model for future studies on the toxic action of organophosphorus pesticides focused on mechanisms, long term and age-related effects. PMID:17382447

  15. Evaluation of the acute toxicity, phytochemical constituents and anti - ulcer properties of methanolic leaf extract of Annona muricata in mice

    Valentine Uneojo Omoja; Thelma Ebele Ihedioha; Gabriel Ifeanyi Eke; Iheanyi K Peter-Ajuzie; Samuel Ekere Okezie

    2014-01-01

    This study investigated the acute toxicity, phytochemical constituents and anti - ulcer properties of methanolic leaf extract of Annona muricata in mice. The anti - ulcer activity was evaluated using absolute ethanol-induced ulcer and aspirin-induced ulcer models in mice. An LD50 of 354.8 +/- 8 mg/kg body weight, bw of the extract was obtained on oral administration. Investigation of the phytochemical constituents of the plant extract revealed the presence of saponins, alkaloids and traces of...

  16. Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

    2013-08-01

    The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. PMID:23606235

  17. Microbial transformation from normal oral microbiota to acute endodontic infections

    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.

  18. Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia chebula Rezt. in rats

    W Panunto

    2010-12-01

    Full Text Available Summary: Terminalia chebula Retz. has been extensively used in traditional medicine for laxative, carminative, astringent, expectorant, and tonic. The chronic toxicity of water extract has not yet been studied. To evaluate its safety, the water extract from the dried fruits of T. chebula was orally administrated in rats. For acute toxicity, a single oral administration was performed at a dose of 5,000 mg/kg body weight (five females, five males. The study of chronic toxicity was determined by oral feeding both female and male rats (ten females, ten males daily with the test substance at the dose of 300, 600 and 1,200 mg/kg body weight continuously for 270 days. The results of acute toxicity showed no signs of toxicity such as general behavior changes, mortality, changes on gross appearance or histophatological changes of the internal organs of rats. The examinations of signs of chronic toxicity showed no abnormalities in the test groups as compared to the controls. Hematological and blood chemical values in treated groups were normal in comparison with the control group. Non-toxicity effect of T. chebula was present as no changes in body weight, internal organ weight, and general behaviors. Macroscopic or microscopic of internal organs or tissues in treated rats showed no changes. Therefore, the water extract of T. chebula given orally to female and male rats did not produce both acute and chronic toxicities in rats. Industrial relevance: The use of medicinal plants and preparations derived from them as dietary supplements, nutraceuticals, functional foods and herbal medicinal products has become more widely accepted in developing countries. Therefore, it is important to evaluate the adverse effects of these plants and their preparations. Among them, T. chebula has received high attention because decoction of its fresh and dried fruits is used in traditional medicine for the treatment of several illnesses such as laxative, carminative

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

    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.

  20. Radiation therapy in prostate cancer: evaluation of acute toxicity

    Goals: The present work documents the increasing demand of curative intent radiation therapy (CIRT) for localized prostate cancer and assesses acute reactions caused by ionizing radiation to intrapelvic organs. Patients and methods: From January 1995 to December 2001, 166 patients with prostatic cancer received radiation therapy, 70% of them (n=116) with curative intent. Treatment was completed as planned in 108 patients: 55 with pelvic irradiation and prostatic boost (PRT), 42 with three-dimensional conformal radiotherapy (3DCRT), 10 with a permanent 125 I implant (IPI) and 1 with combined radiotherapy. Patients were classified as at high- or low-risk according to tumor volume, Gleason score, regional lymph node status and pretreatment specific prostatic antigen level. High-risk patients were assigned to PRT and low-risk patients to local treatment only (either 3DCRT or IPI). Mean doses were 46 Gy for pelvis and 73 Gy for prostate with PRT; 75 Gy with 3DCRT and 127 Gy with IPI and combined radiation therapy. Acute rectal toxicity (ART) and acute urinary toxicity (AUT) were assessed according to the RTOG scale. Statistical analysis was performed with Fischer's exact test. Results: The proportion of patients receiving CIRT increased from 46% (n=28) in 1995-1998 to 84% (n=88) in 1999-2001; p < 0.0001. No patient developed ART or AUT beyond degree 2. ART was lower with 3DCRT (71% degree 0 or 1) than with PRT (45% degree 0 or 1); p= 0.0134. No significant difference was found in AUT. Conclusions: In recent years the demand for CIRT has almost doubled, with a concomitant decrease in palliative radiotherapy. In high-risk patients, pelvic irradiation increased mild and moderate ART, without compromising their life quality. None of the techniques employed was associated with severe acute toxicity. (author)

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

    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)

  2. Acute Toxicity Studies of Brucea javanica Merril Leaves Extract on Mice

    Marissa Angelina

    2012-05-01

    Full Text Available The objective of the study was to evaluate the oral acute toxicity of Brucea javanica Merril extract on both Male and Female DDY-Mice. Brucea javanica leaves have activity as a cytotoxic, anti-diarhhea, etc. Brucea javanica leaves extract was administered orally for first 24 hours at various dose levels (562.5mg/kg bw, 1125 mg/kg bw, 2250 mg/kg bw, and 4500 mg/kg bw to determine the toxicity effects. The treatment groups were compared to the normal control. Vital organs (liver, heart, lymph, lungs, etc and body weight were analyzed to study the toxicity. LD50 determined using Reed and Munich formula. Vital organs average weight showed no difference between control group and treatment groups from the lowest dose until the highest dose. In addition, the body weight data showed no difference between control group and treatment groups. LD50 for Brucea javanica extract using Reed and Munich formula was 1003.65 mg/kg bw. The result of the study showed that extract were categorized as “slightly toxic”.

  3. Acute toxicity study and antipyretic effect of the brown alga Turbinaria conoides (J. Agardh) Kuetz.

    Kumar, S Sadish; Kumar, Y; Khan, M S Y; Anbu, J; Sam, K G

    2009-01-01

    The active principles of brown alga, Turbinaria conoides (J.Agardh) Kuetz. (Sargassaceae) was extracted with n-hexane, cyclohexane, methanol and ethanol-water (1:1) and investigated for acute toxicity and antipyretic activity. Phytochemical analysis of the extracts revealed the presence of steroids, flavonoids and reducing sugars. Acute toxicity study was performed in Wistar rats after administration of extracts orally. No mortality was observed up to the dose of 5 g/kg for methanol and ethanol-water (1:1) extracts whereas n-hexane and cyclohexane extracts were found to be toxic at the dose levels of 1 g/kg and 2 g/kg respectively. In biochemical analysis, n-hexane, cyclohexane and ethanol-water (1:1) extracts caused a significant (P<0.01) increase in serum cholesterol, protein and alkaline phosphatase levels. In haematological studies, a significant difference was observed for cyclohexane and ethanol-water (1:1) extracts in polymorphs, lymphocytes and eosinophils when compared to the control. Antipyretic activity of extracts (100-400 mg/kg doses) was carried out on yeast-induced pyrexia in rats. Cyclohexane extract exhibited more significant antipyretic activity (P<0.01) than the other extracts at a dose of 200 mg/kg (54.43%), which was comparable to that of paracetamol at a dose of 33 mg/kg. The findings validated the use of this brown alga in traditional cure of children's fever. PMID:20448848

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

    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)

  5. 微囊藻毒素-LR对SD大鼠的短期毒效应研究%The Acute Toxic Effects of Oral Aministration of Microcystin LR in SD Rats

    李秀娣; 毛光明

    2013-01-01

      To explore the damage and possible toxicological mechanisms of microcystin-LR (MC-LR) in SD rats. Low and high toxic dose pure MC-LR were added to the drinking water of SD rats. Body weight ,organ index,liver and renal function and oxidative stress indicators were examined at 1,7 and 14 d after feeding. The body weights of high toxic group were significantly lower than low toxic group and control group. In high toxic group,a significant increase in liver and renal index,aspartate aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),Creatinine (Cr) and blood urea nitrogen (BUN) were observed 7 and 14 days after feeding. A significant increase in blood catalase (CAT) and superoxide dismutase (SOD) at 1,7d and a significantly decrease in CAT and SOD at 14d were observed. The malonaldehyde (MDA) significantly increased at 7 and 14 d compared to low toxic group and control group. In low toxic group ,a significant increase of CAT and SOD were observed at 7 d compared to control group ,and maintain this level. The MDA significantly increased at 7 and 14 d compared to control group. After short-term continuous drinking water with 80μg/L MC-LR,the antioxidant systems of SD rats were inhibited,the cells were attacked followed with liver damage and kidney insufficiency. After short-term continuous drinking water with 8μg/L MC-LR,the antioxidant systems of SD rats were impaired but there were no significant liver damage or kidney insufficiency. MC-LR can accumulate in the body.%  探讨微囊藻毒素-LR污染饮用水后,对大鼠机体的损伤和可能的作用机制。通过对大鼠的饮用的蒸馏水中添加低毒和高毒剂量的纯MC-LR,测定其在饲养1、7、14 d的体重、脏器系数、肝肾功能和氧化应激相关指标。高毒组饲养后体重显著低于对照组和低毒组。第7天和第14天肝脏系数、肾脏系数、ALT、AST、ALP、Cr、BUN均显著升高。CAT和SOD先显著升高再显著下

  6. Treatment of recurrent toxic shock syndrome with oral contraceptive agents.

    McIvor, M E; Levin, M L

    1982-09-01

    The case of a 20-year old woman who was hospitalized for toxic shock syndrome (TSS) for 4 consecutive months despite use of conventional therapy for prevention of recurrence is described. Following discharge after the 4th episode she was started on oral contraceptives (OCs), and her next 8 menstrual cycles were uneventful despite continued use of tampons. She since discontinued use of tampons and remains asymptomatic. TSS recurrences occur in 30-64% of patients and can follow the initial episode by up to 41 months. The experience of this patient demonstrates the limitations of using antistaphyloccal antibiotics at the end of each menstrual cycle but suggests that hormonal manipulation may be an effective alternative therapy for TSS recurrences. Epidemiological studies show TSS patients use OCs less frequently than controls. Whether OCs suppress the vaginal flora, as some evidence suggests, or make conditions less favorable for the development of TSS in some other way is unknown. OC therapy for recurrences of TSS should receive further study. PMID:7144265

  7. Intestinal toxicity of oral warfarin intake in rats.

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Zolotarevski, Lidija; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2016-08-01

    Though warfarin is extensively used in the prevention and treatment of thromboembolic processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and 3.5 mg/l) intake on rat's gut were examined. Both doses resulted in prolongation of prothrombin time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria, changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells, suggests commitment of MLN to the suppression of all inflammatory activities and creation of the microenvironment which is non-permissive for induction of potentially harmful immune response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin therapy. PMID:27181730

  8. Toxicidad Oral Aguda de un Fertilizante Foliar (Sharp Oral toxicity of a Fertilizer to Foliate

    Jiménez Parada, Graciela

    2006-04-01

    Full Text Available Se evaluó la Toxicidad Oral Aguda por el método de las Clases de Toxicidad (CTA, de un fertilizante foliar que se identifica como un fertilizante líquido de acción rápida, se aplica en el suelo o por aspersión foliar de acuerdo con el tipo de planta, de su estado fisiológico y uso. Los resultados se analizaron como indica la metodología de la Organización para la Cooperación y Desarrollo Económico (OECD # 423. Para este estudio se emplearon como modelo animal ratas Sprague Dawley. Se detectaron signos de toxicidad evidentes y muerte de animales experimentales en el nivel de dosis de 2000 mg/Kg, no siendo así en el nivel inmediato inferior, 200mg/Kg, por lo que se considera que estos signos de toxicidad observados son inherentes al producto aplicado. Se clasifica a la sustancia en estudio como Peligrosa, en la especie animal utilizada y los niveles de dosis empleados. ABSTRACT.- The Sharp Oral Toxicity was evaluated by the method of the Classes of Toxicity (CTA, of a fertilizer to foliate that it is identified as a liquid fertilizer of quick action, it is applied in the floor or for aspersion to foliate of agreement with the plant type and its physiologic state. The results were analyzed like it indicates the methodology of the Organization for the Cooperation and Economic Development (OECD #423. For this study they were used like model animal rats Sprague Dawley. Evident toxicity signs and death of experimental animals were detected in the level of dose of 2000 mg/Kg, not being this way in the inferior immediate level, 200mg/Kg, for what is considered that these observed toxicity signs are inherent to the applied product. It is classified to the substance in study as Dangerous, in the used animal species and the used dose levels.

  9. Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia.

    Jacoby, Meagan A; Martin, Michael G; Uy, Geoffrey L; Westervelt, Peter; Dipersio, John F; Cashen, Amanda; Stockerl-Goldstein, Keith; Vij, Ravi; Luo, Jingqin; Reineck, Teresa; Bernabe, Noel; Abboud, Camille N

    2014-05-01

    Clofarabine has shown activity and tolerability in older patients with acute myeloid leukemia (AML). We investigated the safety and tolerability of an oral formulation of clofarabine for consolidation therapy of patients aged 60 and older with AML. In this phase I study, twenty-two patients older than 60 years with AML in first complete remission were treated once daily with oral clofarabine for 14 or 21 days of a 28-day cycle, for up to five cycles. Dose escalation from 1 mg to 6 mg daily using a 3 + 3 design was used to determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and tolerability of oral clofarabine. No DLTs or Grade 3-4 nonhematologic toxicities were observed. The primary toxicities were hematologic, including uncomplicated grade 3-4 neutropenia (50%) and thrombocytopenia (50%). Given that myelosuppression necessitating dose delays/reductions was observed more commonly at higher doses, the recommended phase II dose is 2 mg daily for 21 of 28 days. At doses equal to or greater than 2 mg, the median relapse-free survival was 28.35 months. Oral clofarabine was well-tolerated with encouraging activity in patients older than 60 years. Further investigation of oral clofarabine as a consolidation and/or maintenance therapy in AML for older individuals is warranted. (ClinicalTrials.gov:NCT00727766). PMID:24415560

  10. Assessing acute toxicities of pre- and post-treatment industrial wastewaters with Hydra attenuata: A comparative study of acute toxicity with the fathead minnow, Pimephales promelas

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. (E.I. DuPont de Nemours and Co., Newark, DE (United States). Haskell Lab. for Toxicology and Industrial Medicine)

    1994-04-01

    This study was undertaken to (a) determine wastewater treatment effectiveness using two freshwater organisms, (b) compare acute toxicity results from the two species exposed to the wastewaters, and (c) link acute and potential developmental toxicity of wastewaters in one organism. The acute toxicities of several pretreatment and post-treatment industrial waste-water samples wee evaluated with adult Hydra attenuata and fathead minnows. The acute LC50s agreed closely when results in Hydra attenuata were compared with those from fathead minnow tests. Acute LC50s ranged from 3 to >100% of samples with hydra, and from 1.0 to >100% of sample with fathead minnows. The results provided strong evidence of treatment effectiveness because toxicity decreased with progressive stages of treatment. Previously the Hydra Developmental Toxicity Assay was used as a prescreen mainly for in vitro assessment of developmental toxicity with pure compounds and to prioritized toxicants according to selective toxicity to the developing embryo. Recently the authors modified the assay for testing natural waters and wastewaters; hence, some of the wastewater samples also were tested for their developmental toxicity. In this case, the relative selective toxicity of these wastewater samples ranged from 0.7 to 2.1, indicating that no sample was uniquely toxic to the developing embryo, although acute toxicity was manifested. Overall, their results indicate the Hydra Assay functions appropriately in assessments of acute and developmental toxicity of industrial wastewaters and may be a simple and useful tool in a battery of tests for broader scale detection of environmental hazards.

  11. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

    Elham Farsi

    2013-06-01

    Full Text Available OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg.

  12. Non-animal Replacements for Acute Toxicity Testing.

    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. PMID:26256397

  13. Oral microbiota species in acute apical endodontic abscesses

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

    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 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 were not commonly

  14. Toxicity levels to humans during acute exposure to hydrogen fluoride

    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

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

    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)

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

    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)

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

    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...

  18. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão in Rodents

    Marco Antonio Costa

    2013-01-01

    Full Text Available Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2 from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg·kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg·kg−1. In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

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

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

    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....

  20. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to ...

  1. Acute and repeated dose (28 days) oral safety studies of ALIBIRD in rats.

    Anadón, Arturo; Martínez, María A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo, Nieves; Olano, Agustin; Montilla, Antonia; Recio, Isidra; Martínez-Maqueda, Daniel; Miralles, Beatriz; Fornari, Tiziana; García-Risco, Mónica R; Gonzalez, Monserrat; Reglero, Guillermo

    2013-07-01

    ALIBIRD, a test substance composed of oligosaccharides derived from lactulose, a hydrolysate of a whey protein concentrate, and a supercritical extract of rosemary (1:0.5:0.05), was prepared in the laboratory and evaluated for its safety as a multifunctional food additive. In oral toxicity studies (acute and 28 days repeated dose) using Wistar rats, ALIBIRD was administered in a single oral gavage dose of 2,000 mg/kg of body weight and resulted in no adverse events or mortality; a daily dose of 2,000 mg/kg of body weight for 28 days by gavage also resulted in no adverse effects or mortality. No abnormal clinical signs, behavioral changes, body weight changes, or changes in food and water consumption occurred in either study. There were no changes in hematological and serum chemistry values, organ weights, or gross or histological characteristics. Based on test results, it is concluded that ALIBIRD is well tolerated in rats at an acute and subchronic (28 days) dose of 2,000 mg/kg of body weight. PMID:23834798

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

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit;

    2016-01-01

    toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall......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...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis...

  3. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%

  4. Effect of Oral Ondansetron on Decreasing the Vomiting Associated with Acute Gastroenteritis in Iranian Children

    Haniyeh Mohammadpour; Saman Rezaieian; Hamidreza Badeli; Kioomars Golshekan; Afagh Hassanzadehrad

    2013-01-01

    Objective: The aim of this study was to determine the effect of oral ondansetron in decreasing the vomiting due to acute gastroenteritis in children.Methods: In a single center, randomized, double blind, controlled trial, the effect of oral ondansetron was compared with placebo on 176 patients between 1 and 10 years old with acute gastroenteritis. 30 minutes after drug administration, oral rehydration therapy (ORT) was initiated. Severity of vomiting was evaluated during emergency department ...

  5. The Impact of Oral Health on Taste Ability in Acutely Hospitalized Elderly

    Solemdal, Kirsten; Sandvik, Leiv; Willumsen, Tiril; Mowe, Morten; Hummel, Thomas

    2012-01-01

    Objective To investigate to what extent various oral health variables are associated with taste ability in acutely hospitalized elderly. Background Impaired taste may contribute to weight loss in elderly. Many frail elderly have poor oral health characterized by caries, poor oral hygiene, and dry mouth. However, the possible influence of such factors on taste ability in acutely hospitalized elderly has not been investigated. Materials and Methods The study was cross-sectional. A total of 174 ...

  6. Sub-acute Toxicity of Aqueous Fruit Pulp Extract of Hunteria umbellata in Albino Wistar Rats.

    Igbe, Ighodaro; Eze, Gerald Ikechi; Ojameruaye, Oghenekevwe

    2013-01-01

    Hunteria umbellata K. Schum (Apocynaceae) is used in herbal medicine for the treatment of diabetes, peptic ulcers, piles, yaws, dysmenorrhea, fevers, infertility, and helminthic infections. The present study investigated the in vivo sub-acute toxicity of the aqueous fruit pulp extract of Hunteria umbellata (H. umbellata). Sub-acute toxicity was evaluated after administering daily oral doses of 200, 400 and 800 mg/kg of H. umbellata extract, for 28 days to the rats. Anthropometric, biochemical, hematological and histopathological parameters were assessed using standard procedures. There were significant reductions (p<0.01) in the pattern of weight gain in 200 and 400 mg/kg H. umbellata -treated rats but no significant differences in the organ weight index between control and treated animals. Hematological and biochemical analysis showed no marked differences in any of the parameters examined in either the control or treated groups but there was significant (p<0.05) thrombocytosis. Pathologically, neither gross abnormalities nor histopathological changes were observed. H. umbellata led to activation of the reticulo endothelial tissue of the spleen as evidenced by proliferation of the sinus histocytes and activation of the lymphoid aggregates in the lungs, indicating activation of the local immune system of the lungs. H. umbellata fruit pulp is relatively nontoxic in animals but there is increased tendency to cause thrombocytosis on prolonged use. PMID:23955412

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

    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.

  8. Acute toxicity and the effect of andrographolide on Porphyromonas gingivalis-induced hyperlipidemia in rats.

    Al Batran, Rami; 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 ×10(12) 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 < 0.05). 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. PMID:23844365

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

    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.

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

    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.

  11. Antihyperglycaemic effect and acute toxicity of Securigera Securidaca L. seed extracts in mice.

    Hosseinzadeh, H; Ramezani, M; Danaei, A R

    2002-12-01

    The antihyperglycaemic activity of a Securigera securidaca aqueous infusion and an ethanol maceration extract of seeds was studied in normoglycaemic, glucose-induced hyperglycaemic and alloxan-induced diabetic mice. The acute toxicity of the ethanol extract was more than that of the aqueous one. The phytochemical analysis showed that the seed extracts were rich in flavonoids. The intraperitoneal and oral administration of the aqueous and ethanol extracts significantly reduced blood glucose in alloxan-induced diabetic mice. In normoglycaemic and glucose-induced hyperglycaemic mice, the blood glucose levels were not significantly different from the control. Glibenclamide was not able to lower blood glucose in alloxan-induced diabetic mice, while it significantly lowered the blood sugar in normoglycaemic mice. The results indicate that S. securidaca seed extracts significantly reduce blood glucose in alloxan-induced diabetic mice by a mechanism different from that of sulfonylurea agents. PMID:12458478

  12. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R.

    2014-01-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary test...

  13. Oral Zinc Supplementation for the Treatment of Acute Diarrhea

    Sh Gheibi

    2014-04-01

    Full Text Available Introduction: Diarrheal diseases are a serious health problem and important causes of growth retardation and death in the developing world, especially those of prolonged duration. Since diarrhea is constantly found in children with zinc deficiency, very studies supported zinc supplements beneficial on the duration and severity of diarrhea among children. We review the impact of zinc effects on diarrhea in South-West Asia to update the evidences and to assess its effect on the global burden of diarrhea.   Materials and Methods: We conduct a systematic review through January 2014, for randomized controlled trials relevant to effect of zinc on diarrhea in children. We searched the MeSH terms zinc, acute gastroenteritis and children from various databases of Cochrane Library and PubMed, then clinical trials done in South-West Asia, selected for making written. Results: In recent years, several studies have reported the therapeutic effect of zinc supplementation on diarrheal diseases that was beneficial on decreased episode duration, stool output, stool frequency, hospitalization duration. In some countries in West Asia such as Lebanon, Israel, Saudi Arabia and Iran in clinical trials showed a faster improvement in acute gastroenteritis in children less than five years. But in some countries, such as Turkey, this effect was not significant.   Conclusions: Oral zinc supplementation significantly decreases diarrhea duration and has a greater effect on malnourished children. Zinc supplementation seems to be an appropriate public health strategy, mainly in areas of endemic deficiencies. Global attempts should is increased to support recommended regimen of therapeutic zinc by WHO in all areas. Keywords: Acute Gastroenteritis, Children, Zinc, South-West Asia.  

  14. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

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

    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 14th. 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)

  16. Acute toxicity profile of radiotherapy in 690 children and adolescents: RiSK data

    Background and purpose: The 'Registry for the evaluation of side effects after radiation in childhood and adolescence' (risk) was introduced to characterize adverse effects of radiotherapy in childhood and adolescence prospectively. The aim of this analysis was to characterize the pattern of acute side effects. Materials and methods: Since 2001, patients receiving radiotherapy in one of the German pediatric therapy trials have been registered in RiSK with detailed information regarding radiation doses to organs at risk and characterization of acute toxicities. Results: From 2001 to May 2009, 690 patients have been characterized for acute toxicity in primary therapy. Acute toxicity ≥ grade 1 was observed in 506 patients. In patients irradiated in their lung and liver, patients with grade 1 or 2 acute toxicities showed higher organ volumes exposed to radiation doses <20 Gray (Gy) compared to patients without toxicities. For the salivary glands, there was a positive correlation between the acute toxicity grade and the maximum radiation dose to the organ; the lower GI tract showed a similar trend. The impact of different chemotherapy regimens on these acute side effects remains unclear. Age did not have any impact on side effects. Conclusion: This analysis gives a comprehensive overview of the acute toxicities of radiotherapy in children and adolescents. With prolongation of follow-up, detailed analyses regarding late toxicities will be possible with the characterization of dose-volume-effect relationships.

  17. Acute toxicity and practical value of extended field radiotherapy

    The course of supradiaphragmatic and/or infradiaphragmatic irradiation, which was carried out using the extended field technique in 198 patients diagnosed with non-hodgkin lymphomas or hodgkins disease, was investigated for side-effect levels and required interruptions and withdrawals of treatment. Further studies had the aim to elucidate the acute toxicity of field-integrated dose modification as compared to that associated with the conventional diaphragmatic technique. The available body of evidence appears to suggest that dose-modified irradiation, rather than giving rise to a greater number of acute side-effects, permitted a stricter adherence to treatment plans and reduced the need for interruptions and withdrawals, even though the individual dose and, thus, the oncolytic effect of irradiation was increased. Using field-integrated dose modification, more stringent therapeutic strategies could be followed even in complicated cases. As fas as radiobiology is concerned, it is to be expected for dose-modified irradiation that the frequency of delayed effects will be reduced. (orig./Vhe)

  18. Feasibility and acute toxicities of radioimmunoguided prostate brachytherapy

    Purpose: We present a technique that fuses pelvic CT scans and ProstaScint images to localize areas of disease within the prostate gland to customize prostate implants. Additionally, the acute toxicity results from the first 43 patients treated with this technique are reviewed. Methods and Materials: Between 2/97 and 8/98, 43 patients with clinical stage II prostate adenocarcinoma received ultrasound-guided transperineal implantation of I-125 or Pd-103 seeds. The median patient age was 70 years (range 49-79). Prior to treatment, the median Gleason score and prostate-specific antigen (PSA) were 6 (range 3-8) and 7.5 (range 1.8-16.6 ng/mL), respectively. The median follow-up was 10 months (range 2.9-20.4 months). Results: The median PSA value at 10 months is 0.7 ng/mL. Significant acute complications within the first month following implantation included 13 Grade I urinary symptoms, 24 Grade II urinary symptoms, 6 Grade III symptoms, and no Grade IV complications. Beyond 4 months, complications included 12 Grade I urinary symptoms, 17 Grade II urinary symptoms, 1 Grade III, and 1 Grade IV complications. Conclusions: The image fusion of the pelvic CT scan and ProstaScint scans helped identify regions within the prostate at high risk of local failure, which were targeted with additional seeds during implantation

  19. CT and MR manifestations of acute methyl alcohol toxic encephalopathy

    Objective: To analyze the CT and MR manifestations of methyl alcohol toxic encephalopathy and to improve the diagnosing value of CT and MRI. Methods: 40 patients with methyl alcohol intoxication were collected in this study, in which CT scan was performed on 40 cases and MRI on 4 cases. All CT and MRI radiological data of brain were retrospectively studied. Results: 13 of 40 cases showed abnormal findings on brain CT and MRI. The most common manifestation (6/13, 46%)was hypodensity in frontal parietal white matter and external capsule-putamen on CT, which showed long or short T1 and long T2 on MR. Hemorrhage in right putamen was found only in 1 patient (1/13,7%). CT showed low density inbilateral external capsule in 4 cases (4/13,31%), in which MR showed long or short T1 and long T2. Low density lesions in subcortical white matter of bilateral frontal and parietal lobes, cingulate gyms and insular lobes were found in 2 patients (2/13,15%). The more severe clinic manifestation, the more obvious brain lesion CT and MRI showed. Conclusion: Brain CT and MR manifestations have great diagnostic value of acute methyl alcohol toxic encephalopathy. MRI was more sensitive and better than CT in finding early brain damage caused by methanol intoxication. (authors)

  20. Acute toxicity of heavy metals towards freshwater ciliated protists

    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 LC5 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, LC5) and lead (0.12 mg l-1, LC5), whilst E. aediculatus showed the highest sensitivity for nickel (0.03 mg l-1, LC5). 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

  1. Acute toxicity study of stone-breaker (Phyllanthus tenellus Roxb.

    Tássia Campos de Lima e Silva

    2012-04-01

    Full Text Available Phyllanthus tenellus Roxb. is a herbaceous plant native to Brazil and appears frequently in humid environments. This plant is used to treat urolithiasis, inflammatory bowel disease, diabetes and hepatitis B. The acute toxicity and LD50 of an aqueous extract of P. tenellus were determined in laboratory mice and their behavior was analyzed. The intraperitoneal LD50 was calculated by the Karber & Behrens (1964 method, for which a 96% alcoholic extract was concentrated in a rotary evaporator. Male albino mice (Mus musculus were divided into three batches of six animals and observed for 24 hours after administration of the extract, diluted in 0.9% saline, at doses of 500, 1000, 1500, 2000 and 2500 mg / kg. Short-term studies have demonstrated this plant to be non-toxic; however, we found that this species induced agitation in animals, with stereotyped movements, spasms and increased respiratory frequency, as well as signs of depression, such as sleepiness, prostration, dyspnea and a reduction in respiratory frequency.

  2. 40 CFR 799.9110 - TSCA acute oral toxicity.

    2010-07-01

    ..., testing in animals of the other sex may be dispensed with. An acceptable option would be to test at least... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING...

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

    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 LC50, one third of the LC01) to all copper treatments decreased the copper 96 h LC50 by 58%, while sublethal copper exposure (6% of the copper LC50, 13% of the LC01) decreased the cadmium 96 h LC50 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 ion homeostasis

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

    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)

  5. Oral cadmium chloride intoxication in mice

    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 effec...

  6. Evaluation of acute and subacute toxicity induced by methanol extract ofTerminalia citrina leaves in Sprague Dawley rats

    Narhari Das; Durajan Goshwami; Md. Sharif Hasan; Sheikh Zahir Raihan

    2015-01-01

    Objective: To evaluate acute and subacute toxicity of methanol extract ofTerminalia citrina leaves (family: Combretaceae) in Sprague Dawley rats. Methods: The acute toxicity studies were conducted where the limit test dose of 3 200 mg/kg body weight used. Observations were made and recorded systemically on 1, 2, 4, 24 and 48 h after dose administration for behavior, breathing, cutaneous effects, sensory nervous system response or gastrointestinal effects. For the subacute toxicity, four groups of 10 female rats were received; distilled water (control), 250, 500 and 1 000 mg/kg of extracts respectively every 24 h orally for 28 days. Results: No significant variation in the body and organ weights between the control and the treated group was observed after 28 days of treatment. Haematological analysis and biochemical parameters revealed no toxic effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed. No mortality was recorded in 28 days. Conclusions: It was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

  7. Effects of oral montelukast on airway function in acute asthma.

    Cýllý, A; Kara, A; Ozdemir, T; Oğüş, C; Gülkesen, K H

    2003-05-01

    Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within 1 h of ingestion. This study was undertaken to compare the effects on peak expiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration. Seventy asthmatic patients (FEV1 40-80% predicted and > or = 15% improvement after inhaled beta agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1 mg/kg), intravenous prednisolone (1 mg/kg) or placebo in a randomised fashion. The patients received one ofthe above three groups of medication before any other treatments. This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during 1 h as described in the consensus statement. Thereafter, patients were observed for 24 h to document the effects on PEFR, Borg dyspnoea score and need for rescue medication. The primary end point was percentage change at different time points. Secondary end points were Borg dyspnoea score and use of rescue medication. Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (P<0.05). The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance. Furthermore, montelukast plus prednisolone group required less inhaled short-acting beta agonistthan other two groups. The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions. PMID:12735671

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

    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.

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

    Dutok, Carlos M. S.; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M. C.

    2015-01-01

    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. PMID:26273696

  10. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    Matthew Sean Peach

    2015-01-01

    Full Text Available A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.

  11. The impact of oral health on taste ability in acutely hospitalized elderly.

    Kirsten Solemdal

    Full Text Available OBJECTIVE: To investigate to what extent various oral health variables are associated with taste ability in acutely hospitalized elderly. BACKGROUND: Impaired taste may contribute to weight loss in elderly. Many frail elderly have poor oral health characterized by caries, poor oral hygiene, and dry mouth. However, the possible influence of such factors on taste ability in acutely hospitalized elderly has not been investigated. MATERIALS AND METHODS: The study was cross-sectional. A total of 174 (55 men acutely hospitalized elderly, coming from their own homes and with adequate cognitive function, were included. Dental status, decayed teeth, oral bacteria, oral hygiene, dry mouth and tongue changes were recorded. Growth of oral bacteria was assessed with CRT® Bacteria Kit. Taste ability was evaluated with 16 taste strips impregnated with sweet, sour, salty and bitter taste solutions in 4 concentrations each. Correct identification was given score 1, and maximum total taste score was 16. RESULTS: Mean age was 84 yrs. (range 70-103 yrs.. Total taste score was significantly and markedly reduced in patients with decayed teeth, poor oral hygiene, high growth of oral bacteria and dry mouth. Sweet and salty taste were particularly impaired in patients with dry mouth. Sour taste was impaired in patients with high growth of oral bacteria. CONCLUSION: This study shows that taste ability was reduced in acutely hospitalized elderly with caries activity, high growth of oral bacteria, poor oral hygiene, and dry mouth. Our findings indicate that good oral health is important for adequate gustatory function. Maintaining proper oral hygiene in hospitalized elderly should therefore get high priority among hospital staff.

  12. Rosette nanotubes show low acute pulmonary toxicity in vivo

    W Shane Journeay

    2008-10-01

    Full Text Available W Shane Journeay1, Sarabjeet S Suri1, Jesus G Moralez2, Hicham Fenniri2, Baljit Singh11Immunology Research Group, Toxicology Graduate Program and Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada; 2National Institute of Nanotechnology, National Research Council (NINT-NRC and Department of Chemistry, University of Alberta, 11421 Saskatchewan Drive, Edmonton, AB, T6G 2M9, CanadaAbstract: Nanotubes are being developed for a large variety of applications ranging from electronics to drug delivery. Common carbon nanotubes such as single-walled and multi-walled carbon nanotubes have been studied in the greatest detail but require solubilization and removal of catalytic contaminants such as metals prior to being introduced to biological systems for medical application. The present in vivo study characterizes the degree and nature of inflammation caused by a novel class of self-assembling rosette nanotubes, which are biologically inspired, naturally water-soluble and free of metal content upon synthesis. Upon pulmonary administration of this material we examined responses at 24 h and 7d post-exposure. An acute inflammatory response is triggered at 50 and 25 μg doses by 24 h post-exposure but an inflammatory response is not triggered by a 5 μg dose. Lung inflammation observed at a 50 μg dose at 24 h was resolving by 7d. This work suggests that novel nanostructures with biological design may negate toxicity concerns for biomedical applications of nanotubes. This study also demonstrates that water-soluble rosette nanotube structures represent low pulmonary toxicity, likely due to their biologically inspired design, and their self-assembled architecture.Keywords: nanotoxicology, biocompatibility, nanomedicine, pulmonary drug delivery, lung inflammation

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

    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.

  14. A Comparative Efficacy of Oral Prednisone with Intramuscular Triamcinolone in Acute Exacerbation of Asthma

    Ebrahim Razi Gholam Abbass Moosavi

    2006-03-01

    We conclude that in adults with acute asthma, oral prednisone is more effective than intramuscular triamcinolone LA in improvement of FEV1, but although efficacy of oral prednisone in improvement of FVC is more than intramuscular triamcinolone LA group, this effect is not significant.

  15. THE IMPORTANCE TO RECOGNIZE ORAL MANIFESTATIONS OF ACUTE LEUKEMIA (CASE REPORT)

    Anandina Irmagita; Siti Aliyah Pradono

    2015-01-01

    Dentists could be the first health providers who detect the oral manifestation of early symptoms of leukemia. The management of three cases of acute leukemia, which had intra oral manifestations that were unnoticed by the dentists, are discussed. Before being referred to the Oral Medicine Department, these patients had undergone invasive dental treatment by their dentist, which had caused complication such as bleeding. After being referred, the patients had undergone non-invasive dental exami...

  16. Medical image of the week: acute amiodarone pulmonary toxicity

    Mazursky K

    2015-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 71 year old man with a medical history significant for chronic obstructive pulmonary disease, coronary artery disease with post-operative status coronary artery bypass grafting, heart failure with reduced ejection fraction (25% and atrial fibrillation/flutter underwent an elective ablation of the tachyarrhythmia at another facility and was prescribed amiodarone post procedure. He started complaining of cough and dyspnea one day post procedure and was empirically treated with 2 weeks of broad spectrum antibiotics. He subsequently was transferred to our facility due to worsening symptoms. He also complained of nausea, anorexia with resultant weight loss since starting amiodarone, which was stopped 5 days prior to transfer. Infectious work up was negative. On arrival to our facility, he was diagnosed with small sub-segmental pulmonary emboli, pulmonary edema and possible acute amiodarone toxicity. His was profoundly hypoxic requiring high flow nasal cannula or 100% non-rebreather mask at all times. His symptoms persisted despite ...

  17. ProTox: a web server for the in silico prediction of rodent oral toxicity

    Drwal, Malgorzata N.; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R.; Preissner, Robert

    2014-01-01

    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 me...

  18. Sub-acute toxicity of a hydro-ethanolic whole plant extract of Synedrella nodiflora (L Gaertn in rats

    Samuel Adjei

    2014-01-01

    Full Text Available Objectives: Synedrella nodiflora (L Gaertn (family Asteraceae is traditionally used in Ghana for the management of epilepsy, hiccup and threatened abortion. The anticonvulsant and other related neuro-pharmacological effects of a hydro-ethanolic extract in murine models have been established. To this end, we evaluated a sub-acute toxicity of the hydro-ethanolic whole plant extract in rats. Materials and Methods: The effects of a continuous 14-day oral administration of the extract (100, 300 and 1000 mg/kg on haematological and serum biochemical parameters were measured. Results: The extract produced no mortality in the rats treated during the study period. The extract also did not significantly affect any of the haematological and serum biochemical indices measured. Conclusion: This result suggests that a 14-day oral administration of the hydro-ethanolic extract of Synedrella nodiflora is relatively safe in Sprague-Dawley male rats under the present laboratory conditions.

  19. Importance of structural information in predicting human acute toxicity from in vitro cytotoxicity data

    In this study, we tried to assess the utility of the structural information of drugs for predicting human acute toxicity from in vitro basal cytotoxicity, and to interpret the informative quality and the pharmacokinetic meaning of each structural descriptor. For this, human acute toxicity data of 67 drugs were taken from literature with their basal cytotoxicity data, and used to develop predictive models. A series of multiple linear regression analyses were performed to construct feasible regression models by combining molecular descriptors and cytotoxicity data. We found that although the molecular descriptors alone had only moderate correlation with human acute toxicity, they were highly useful for explaining the discrepancy between in vitro cytotoxicity and human acute toxicity. Among many possible models, we selected the most explanatory models by changing the number and the type of combined molecular descriptors. The results showed that our selected models had high predictive power (R2: between 0.7 and 0.87). Our analysis indicated that those successful models increased the prediction accuracies by providing the information on human pharmacokinetic parameters which are the major reason for the difference between human acute toxicity and cytotoxicity. In addition, we performed a clustering analysis on selected molecular descriptors to assess their informative qualities. The results indicated that the number of single bonds, the number of hydrogen bond donors and valence connectivity indices are closely related to linking cytotoxicity to acute toxicity, which provides insightful explanation about human toxicity beyond cytotoxicity.

  20. Bacterial Diversity in Oral Samples of Children in Niger with Acute Noma, Acute Necrotizing Gingivitis, and Healthy Controls

    Bolivar, Ignacio; Whiteson, Katrine; Stadelmann, Benoît Yves; Baratti, Denise; Gizard, Yann; Mombelli, Andrea; Pittet, Didier; Schrenzel, Jacques

    2012-01-01

    Background Noma is a gangrenous disease that leads to severe disfigurement of the face with high morbidity and mortality, but its etiology remains unknown. Young children in developing countries are almost exclusively affected. The purpose of the study was to record and compare bacterial diversity in oral samples from children with or without acute noma or acute necrotizing gingivitis from a defined geographical region in Niger by culture-independent molecular methods. Methods and Principal F...

  1. Impaired homeostatic mechanism of potassium handling after acute oral potassium load in diabetes mellitus.

    H.J. Kim; Ahn, Y. H.; Park, C H; Kang, C M; Park, H C; Bae, H. Y.; Choi, S. D.

    1993-01-01

    Chronic stable diabetic patients (n = 6) were compared with healthy control subjects (n = 5) after acute oral intake of 50 mEq of potassium chloride (KCl) to investigate for possible derangements of homeostatic responses for acute term (3 hrs) to acute potassium load. Plasma renin activity (PRA), plasma aldosterone (PA), and transtubular potassium concentration gradient (TTKG) known as a useful semiquantative index of distal nephron potassium secretion were measured. All the baseline paramete...

  2. Acute Toxicity-Supported Chronic Toxicity Prediction : A k-Nearest Neighbor Coupled Read-Across Strategy

    Swapnil Chavan; Ran Friedman; Ian A. Nicholls

    2015-01-01

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 7...

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

    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.

  4. Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats

    Hadrup, Niels; Löschner, Katrin; Bergström, Anders;

    2012-01-01

    Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 $, 6 #); Ag-NP at doses: 2...

  5. Transcytosis, Antitumor Activity and Toxicity of Staphylococcal Enterotoxin C2 as an Oral Administration Protein Drug

    Zhao, Wenbin; Li, Yangyang; Liu, Wenhui; Ding, Ding; Xu, Yingchun; Pan, Liqiang; Chen, Shuqing

    2016-01-01

    Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

  6. FISH ACUTE TOXICITY SYNDROMES IN THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS.

    The focus of this report is to summarize the development and status of the fish acute toxicity syndrome (FATS) research effort. hus far, FATS associated with nonpolar narcotics, oxidative phosphorylation uncouplers, respiratory membrane irritants, acetylcholinesterase (AChE) inhi...

  7. Acute toxicity and effect of some petroleum hydrocarbon on the metabolic index in Etroplus suratensis

    Ansari, Z.A.; Farshchi, P.

    Acute toxicity (LC sub(50)) and effect of some petroleum hydrocarbons (Toluene, Quinoline, Pyridine and Naphthalene) on the metabolic index (oxygen consumption rate) of an estuarine fish. Etroplus suratensis is reported. The LC sub(50) values were...

  8. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    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 vin

  9. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  10. ACUTE TOXICITY, PHYTOCHEMISTRY AND ANTIBACTERIAL ACTIVITY OF AQUEOUS AND ETHANOLIC LEAF EXTRACTS OF CASSIA ALATA LINN

    Timothy SY; Lamu FW; Rhoda AS; Adati RG; Maspalma ID; Askira M

    2012-01-01

    Cassia alata Linn is an important medicinal plant as well as an ornamental flowering plant that has diverse reported medicinal values. This study focused on the evaluation of the phytochemical components, antibacterial as well as acute toxicity studies. The leaves of the plant were collected, dried, ground and extracted using 95% ethanol and water. The extracts were used for acute toxicity study, phytochemical screening and antibacterial assay using cup-plate method. The result from this stud...