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

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Basak Ozlem Perk

2013-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

NARCIS (Netherlands)

Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

2011-01-01

BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving

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

Directory of Open Access Journals (Sweden)

Assem Kalykova

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Kjeld Schmiegelow

2017-04-01

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

Acute toxicity and associated mechanisms of four strobilurins in algae.

Science.gov (United States)

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

2018-04-03

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

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

International Nuclear Information System (INIS)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m 3 for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m 3 (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

Energy Technology Data Exchange (ETDEWEB)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

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

OpenAIRE

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

2016-01-01

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

Ecological effects of various toxic agents on the aquatic microcosm in comparison with acute ionizing radiation

International Nuclear Information System (INIS)

Fuma, S.; Ishii, N.; Takeda, H.; Miyamoto, K.; Yanagisawa, K.; Ichimasa, Y.; Saito, M.; Kawabata, Z.; Polikarpov, G.G.

2003-01-01

The purpose of this study was an evaluation of the effect levels of various toxic agents compared with acute doses of ionizing radiation for the experimental model ecosystem, i.e., microcosm mimicking aquatic microbial communities. For this purpose, the authors used the microcosm consisting of populations of the flagellate alga Euglena gracilis as a producer, the ciliate protozoan Tetrahymena thermophila as a consumer and the bacterium Escherichia coli as a decomposer. Effects of aluminum and copper on the microcosm were investigated in this study, while effects of γ-rays, ultraviolet radiation, acidification, manganese, nickel and gadolinium were reported in previous studies. The microcosm could detect not only the direct effects of these agents but also the community-level effects due to the interspecies interactions or the interactions between organisms and toxic agents. The authors evaluated doses or concentrations of each toxic agent which had the following effects on the microcosm: (1) no effects; (2) recognizable effects, i.e., decrease or increase in the cell densities of at least one species; (3) severe effects, i.e., extinction of one or two species; and (4) destructive effects, i.e., extinction of all species. The resulting effects data will contribute to an ecological risk assessment of the toxic agents compared with acute doses of ionizing radiation

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

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Maria Cristina Collivignarelli

2017-09-01

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

Acute and subacute toxicity of Schinus terebinthifolius bark extract.

Science.gov (United States)

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

2009-12-10

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

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

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A.R. Fernandez-Alba

2002-01-01

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

Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

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Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxic Effects of Cannabis and Cannabinoids: Animal Data

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Pierre Beaulieu

2005-01-01

Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

Phytochemical screening, proximate analysis and acute toxicity ...

African Journals Online (AJOL)

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

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

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Liming Zhang

2011-03-01

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

Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

Science.gov (United States)

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

2018-03-01

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

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

African Journals Online (AJOL)

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

Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment

International Nuclear Information System (INIS)

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

2013-01-01

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

Acute oral toxicity test of chemical compounds in silkworms.

Science.gov (United States)

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

2016-02-01

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

[Acute toxicity effects of three red tide algae on Brachionus plicatilis].

Science.gov (United States)

Zhou, Wen-Li; Xiao, Hui; Wang, You; Zhai, Hong-Chang; Tang, Xue-Xi

2008-11-01

Acute toxicity testing method was used to study effects of different density of Prorocentrum donghaiense, Heterosigma akashiwo and Alexandrium tamarense on mortality rates and population growth parameter of Brachionus plicatilis under controlled experimental conditions. Results showed that 24 h LC50 values of Prorocentrum donghaiense, Heterosigma akashiwo and Alexandrium tamarense treatment to mortality rate of Brachionus plicatilis were 3.56, 1.21 and 0.49 (x 10(4) cells/mL) respectively. Marked density effects were presented when three species of red tide microalga showed their toxicity to Brachionus plicatilis. There were significant inhibitory effects on Brachionus plicatilis when it was exposed to cells of Prorocentrum donghaiense at the concentration of 10(4) cells/mL, filtrate and cell contents of Heterosigma akashiwo at the concentration of 10(5) cells/mL, and cells, filtrate and cell contents of Alexandrium tamarense at the concentration of 10(3) cells/mL respectively. Inhibitory effects of three species of microalga on Brachionus plicatilis were enhanced with increasing of microalgal density.

Comparative acute toxicity of shale and petroleum derived distillates.

Science.gov (United States)

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

1989-12-01

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

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

Science.gov (United States)

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

2011-08-01

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

Comparison of the therapeutic effect between sodium bicarbonate and insulin on acute propafenone toxicity.

Science.gov (United States)

Yi, Hwa Yeon; Lee, Jang Young; Lee, Won Suk; Sung, Won Young; Seo, Sang Won

2014-10-01

Unlike other sodium-channel-blocking antiarrhythmic agents, propafenone has β-blocking effects and calcium-channel-blocking effects. Yi et al recently studied insulin's treatment effect on acute propafenone toxicity in rats. However, because the degree of effectiveness of insulin compared to the previously known antidote sodium bicarbonate (NaHCO3) was not studied, the 2 treatment methods were compared for propafenone intoxication in rats. Rats received intravenous propafenone (36 mg/[kg h]) for 12 minutes. After the induction of toxicity, rats (n = 10 per group) received normal saline solution (NSS), NaHCO3, or insulin with glucose as treatment. Animals in the NSS, NaHCO3, and Insulin groups received an intravenous infusion of 36 mg/(kg h) propafenone until death occurred. For each animal, the mean arterial pressure (MAP, heart rate, PR interval, QRS duration, total hemoglobin, sodium, potassium, potential of hydrogen, bicarbonate, glucose, lactate, and central venous oxygen saturation (Scvo2) were measured and compared among the groups. Survival of the Insulin group was greater than that of the NSS group by log-rank test (P = .021). Sodium bicarbonate prevented the decline of MAP for 55 minutes. In comparison, insulin prevented the decline of MAP and heart rate, and the elongation of the PR interval and QRS duration for 55 minutes (P < .05). Propafenone toxicity led to decreased Ca(2+), potential of hydrogen, and Scvo2 and increased lactate levels. Insulin prevented the decrease of Ca(2+) and Scvo2, whereas NaHCO3 prevented the increase in lactate. Insulin treatment was more effective than NaHCO3 on acute propafenone toxicity in rat. Therefore, when propafenone-induced cardiotoxicity occurs, which is unresponsive to current treatment methods, glucose-insulin infusion may be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-03-15

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

Acute and chronic toxic effects of bisphenol A on Chlorella pyrenoidosa and Scenedesmus obliquus.

Science.gov (United States)

Zhang, Wei; Xiong, Bang; Sun, Wen-Fang; An, Shuai; Lin, Kuang-Fei; Guo, Mei-Jin; Cui, Xin-Hong

2014-06-01

The acute and chronic toxic effects of Bisphenol A (BPA) on Chlorella pyrenoidosa (C. pyrenoidosa) and Scenedesmus obliquus (S. obliquus) were not well understood. The indoor experiments were carried out to observe and analyze the BPA-induced changes. Results of the observations showed that in acute tests BPA could significantly inhibit the growth of both algae, whereas chronic exposure hardly displayed similar trend. Superoxide dismutase (SOD) and Catalase (CAT) activities of both algae were promoted in all the treatments. Chlorophyll a synthesis of the two algae exhibited similar inhibitory trend in short-term treatments, and in chronic tests C. pyrenoidosa hardly resulted in visible influence, whereas in contrast, dose-dependent inhibitory effects of S. obliquus could be clearly observed. The experimental results indicated that the growth and Chlorophyll a syntheses of S.obliquus were more sensitive in response to BPA than that of C. pyrenoidosa, whereas for SOD andCAT activities, C. pyrenoidosa was more susceptible. This research provides a basic understanding of BPA toxicity to aquatic organisms. Copyright © 2012 Wiley Periodicals, Inc.

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

Science.gov (United States)

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

2017-06-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-09-15

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

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

International Nuclear Information System (INIS)

Alsop, Derek; Wood, Chris M.

2013-01-01

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

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

Science.gov (United States)

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

Acute and subacute toxicity of 18F-FDG

International Nuclear Information System (INIS)

Dantas, Danielle Maia

2013-01-01

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

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

African Journals Online (AJOL)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-10-15

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

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

Science.gov (United States)

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

1997-01-01

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

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

OpenAIRE

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

1997-01-01

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

Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

Science.gov (United States)

Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

2009-07-01

The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L.

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

Science.gov (United States)

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

2016-12-24

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

Common toxicity criteria: version 2.0. an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy

International Nuclear Information System (INIS)

Trotti, Andy; Byhardt, Roger; Stetz, Joanne; Gwede, Clement; Corn, Benjamin; Fu, Karen; Gunderson, Leonard; McCormick, Beryl; Morris, Mitchell; Rich, Tyvin; Shipley, William; Curran, Walter

2000-01-01

In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v. 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system. A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v. 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities

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

Science.gov (United States)

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

2016-11-25

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

The effect of aerobic exercise on treatment-related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer.

Science.gov (United States)

Kapur, G; Windsor, P M; McCowan, C

2010-09-01

We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference in bladder toxicity scores between the two groups (P=0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.

Predictive acute toxicity tests with pesticides.

Science.gov (United States)

Brown, V K

1983-01-01

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

Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

Directory of Open Access Journals (Sweden)

Jiaying Xu

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

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

Science.gov (United States)

1982-09-10

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

Acute Toxic Myocarditis and Pulmonary Oedema Developing from Scorpion Sting

Directory of Open Access Journals (Sweden)

Cem Sahin

2015-03-01

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

Acute Toxicity Effect of the Leaf Extract of Leptadenia Hastata (Pers ...

African Journals Online (AJOL)

... the LD50 of the aqueous extract of the Leptadenia hastata was calculated using arithmetic method. The acute toxicity signs observed were inappetence, weakness, unsteady gait, polypnoea and asthenia in all the groups; having unsteady gait and polypnoea being more prominent in 800 to 3200mg/Kg bwt treated groups.

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-12-01

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

Antioxidant activity and acute toxicity of Neoglaziovia variegata ...

African Journals Online (AJOL)

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

ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ...

African Journals Online (AJOL)

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

Acute and sub-chronic toxicity studies of honokiol microemulsion.

Science.gov (United States)

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

2015-04-01

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

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

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Haonan Zhou

2016-11-01

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

Effects of Shuang Wuzhen Tong Capsule on acute toxicity of mice caused by swelling and auricular dimethylbenzene

Science.gov (United States)

Hao, Shaojun; Sun, Youshu; Guo, Junyi; Chen, Weiliang; Wang, Hongyu; Sun, Jianhua; Guan, Zhijiang; Zhang, Zhengchen; Wang, Fang

2018-04-01

To observe the effect of Shuang Wuzhen Tong Capsule on acute toxicity of mice caused by swelling and auricular dimethylbenzene. 40 rats, weighing 18 ˜ 22G, half male and half female. Shuang Wuzhen Tong Capsule maximum concentration maximum volume to mice for 1 days by gavage for 1 times, for 7 consecutive days, to observe the situation of animal death, the maximum tolerance; the other 50 mice, were divided into 5 groups, were fed with Shuang Wuzhen Tong capsule suspension, Jingfukang granule suspension and the same volume 0.5%CMC. No death in 7 days. After death animal autopsy, heart, liver, spleen, lung, kidney, brain, stomach, intestine and no important organ obvious bleeding, hyperemia and edema, exudation, ulcer, perforation, pleural, peritoneal, pericardial cavity without effusion. Shuang Wuzhen Tong Capsule group and Jingfukang granule group could obviously reduce the xylene induced swelling of mouse ear, ear swelling degree decreased significantly (P<0.01). Shuang Wuzhen Tong Capsule has no obvious acute toxicity, anti-inflammatory effects.

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

Science.gov (United States)

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

2018-02-05

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

Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

DEFF Research Database (Denmark)

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

2000-01-01

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

Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

International Nuclear Information System (INIS)

Lear, J.L.; Raff, U.; Jain, R.; Horgan, J.G.

1988-01-01

The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

Energy Technology Data Exchange (ETDEWEB)

Rauscher, J.D.

1988-01-01

Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects of Se and Cu on planarians.

Acute toxicity from baking soda ingestion.

Science.gov (United States)

Thomas, S H; Stone, C K

1994-01-01

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

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

Science.gov (United States)

2015-03-17

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

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

OpenAIRE

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

2017-01-01

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

Non-animal Replacements for Acute Toxicity Testing.

Science.gov (United States)

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

2015-07-01

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

The Study on Acute and Subacute Toxicity and Sarcoma-180 Anti-cancer Effects of Carthami Tinctor-Fructus Herbal-acupuncture(CF

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Chang-Suk An

2002-02-01

Full Text Available Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF for LD50 and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12 of mice with Sarcoma-180 cancer cell line. Results: 1. LD50 was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC of rats, compared to the nonnal group.(p<0.05 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell

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

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Eun Kyung Sohn

2015-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

Science.gov (United States)

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

2010-09-01

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

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

International Nuclear Information System (INIS)

Morris, Monica; Powell, Simon

1996-01-01

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

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

NARCIS (Netherlands)

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

2017-01-01

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

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

Science.gov (United States)

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

2016-02-17

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

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

Directory of Open Access Journals (Sweden)

Surender Singh

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Science.gov (United States)

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

2006-12-01

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

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

Science.gov (United States)

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

2014-08-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

African Journals Online (AJOL)

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

Acute toxicity of uranium hexafluoride, uranyl fluoride and hydrogen fluoride

International Nuclear Information System (INIS)

Just, R.A.

1988-01-01

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

Acute inhalation toxicity of carbonyl sulfide

Energy Technology Data Exchange (ETDEWEB)

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

1995-12-01

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

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

CSIR Research Space (South Africa)

Lukhele, LP

2015-01-01

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

Acute and chronic systemic chromium toxicity.

Science.gov (United States)

Gad, S C

1989-10-01

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

Acute Toxicity from Topical Cocaine for Epistaxis: Treatment with Labetalol.

Science.gov (United States)

Richards, John R; Laurin, Erik G; Tabish, Nabil; Lange, Richard A

2017-03-01

Topical cocaine is sometimes used for the treatment of epistaxis, as it has both potent anesthetic and vasoconstrictive properties. Cocaine has unpredictable cardiovascular effects, such as sudden hypertension, tachycardia, coronary arterial vasoconstriction, and dysrhythmia. We report a case of acute iatrogenic cardiovascular toxicity from the use of topical cocaine in a 56-year-old man presenting to the Emergency Department with profound epistaxis. To prepare for cauterization and nasal packing, the patient received 4% topical cocaine-soaked nasal pledgets. He became hypertensive, tachypneic, tachycardic, and dysphoric immediately after administration. To directly counter these adverse hyperadrenergic effects, the patient was given 10 mg intravenous labetalol, a mixed β- and α-blocker. This instantly normalized his vital signs and adverse subjective effects. His epistaxis was successfully treated, and he was discharged 1 h later. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We believe that emergency physicians should be aware of the unpredictable acute cardiovascular toxicity of topical cocaine. Labetalol represents an effective first-line treatment, which, unlike benzodiazepines, directly counters the pharmacologic effects of cocaine and has no respiratory or sedative side effects. Labetalol, with its mixed β/α-blocking properties, also mitigates the potential for "unopposed α-stimulation." Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Liver Failure Secondary to Niacin Toxicity

Directory of Open Access Journals (Sweden)

Marc A. Ellsworth

2014-01-01

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

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

Science.gov (United States)

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

2014-10-28

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

Acute toxicity tests using rotifers. 4. Effects of cyst age, temperature, and salinity on the sensitivity of Brachionus calyciflorus

Energy Technology Data Exchange (ETDEWEB)

Snell, T.W.; Moffat, B.D.; Janssen, C.; Persoone, G. (University of Tampa, Florida (USA))

1991-06-01

Several aspects of the response to toxicants using a standardized toxicity test with the freshwater rotifer Brachionus calyciflorus are described. Test animals are obtained by hatching cysts which produce animals of similar age and physiological condition. The acute toxicity of 28 compounds is described with 24-hr LC50's. The LC50's span five orders of magnitude, from silver at 0.008 mg.liter-1 to benzene at more than 1000 mg.liter-1. Control mortality in 84 tests averaged 2% with a standard deviation of 3%, indicating very consistent test sensitivity. Only once in 84 trials did a test fail because of excessive control mortality, yielding a failure rate of 1.2%. Cyst age from 0 to 18 months had no effect on the sensitivity of neonates to reference toxicants. Both high and low temperatures increased rotifer sensitivity to reference toxicants. Copper sensitivity was greater at 10, 25, and 30 degrees C compared with results at 20 degrees C. Likewise, sodium pentachlorophenol toxicity was greater at 10 and 30 degrees C compared with results at 20 degrees C. Survivorship curves at 25 degrees C of neonates under control conditions indicated that mortality begins at about 30 hr. This places a practical limit on toxicant exposure for the assay of 24 hr. B. calyciflorus cysts hatch at salinities up to 5 ppt and acute toxicity tests using pentachlorophenol at this salinity yielded LC50's about one-half those of standard freshwater. B. calyciflorus is preferred over Brachionus plicatilis for toxicity tests in salinities up to 5 ppt because it is consistently more sensitive.

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

OpenAIRE

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

2016-01-01

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

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

African Journals Online (AJOL)

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

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

Directory of Open Access Journals (Sweden)

Xie Shuyu

2011-11-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-10-01

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

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

International Nuclear Information System (INIS)

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

1995-01-01

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

Acute and subacute toxicity of 10B-paraboronophenylalanine

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Directory of Open Access Journals (Sweden)

Arin S. Jantz

2013-01-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

International Nuclear Information System (INIS)

Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea; Zapf, Antonia; Pradier, Olivier; Schmidberger, Heinz

2009-01-01

Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

Energy Technology Data Exchange (ETDEWEB)

Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

2009-09-15

Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

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

International Nuclear Information System (INIS)

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

1995-01-01

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

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

Science.gov (United States)

Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

2014-10-01

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

Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

Science.gov (United States)

Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

2011-05-01

From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

Acute and chronic arsenic toxicity

OpenAIRE

Ratnaike, R

2003-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Acute and subacute toxicity of 18F-FDG

International Nuclear Information System (INIS)

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

2013-01-01

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

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

African Journals Online (AJOL)

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

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

Science.gov (United States)

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

2016-04-01

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

Toxicity and antinociceptive effects of Hamelia patens

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Angel Josabad Alonso-Castro

Full Text Available Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae, a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg was evaluated in acute (14 days and subacute (28 days assays. In the subacute assay, a blood analysis (both hematology and chemistry was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg were evaluated using thermal-induced nociception (hot plate and the chemical-induced nociceptive tests (acid acetic and formalin. In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o. showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17% and 200 mg/kg (25% showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

Assessment of acute toxicity of water soluble fraction of diesel on ...

African Journals Online (AJOL)

Acute toxicity of water soluble fraction (WSF) of diesel fuel was assessed by evaluating its effects on growth of two marine microalgae, Isochrysis and Chaetoceros. Pure cultures of each of the two microalgae were exposed to concentrations of 0% (controls), 5%, 10%, 15% and 20% of diesel WSF (in triplicates) and allowed ...

An evaluation of acute toxicity of colloidal silver nanoparticles.

Science.gov (United States)

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

2011-11-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Study on acute toxicity of anti-vertigo granule on mice

Science.gov (United States)

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

2018-04-01

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

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

International Nuclear Information System (INIS)

Ermin Katrin; Winarti Andayani; Susanto; Hendig Winarno

2014-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

African Journals Online (AJOL)

Erah

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

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

Science.gov (United States)

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

2017-06-01

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

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

NARCIS (Netherlands)

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

2014-01-01

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

Determination of acute toxicity and the effects of sub-acute concentrations of CuO nanoparticles on blood parameters in Rutilus rutilus

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Abdolreza Jahanbakhshi

2015-07-01

Full Text Available Objective(s:Copper oxidenanoparticles have different industrial applications so it is inevitable that nanoparticulate products finally find their way into aquatic ecosystems. Nevertheless there is little information available about their effects on some of edible fish. The present study aims to determine the acute toxicity and evaluate the effect of two sub-acute concentrations (50 and 70% 96 h LC50 of CuO-NPs on some hematological and biochemical parameters of R. rutilus. Materials and Methods:225 healthy specimen of R. rutilus (mean weight 5.52±1.2 g; mean length 6.20±0.2 cm were transported to the laboratory. In order to prepare the stock solution, CuO-NPs was dispersed in pure water with ultrasonication (50-60 kHz for 15 min every day before dosing. At first, R. rutilus was exposed to CuO-NPs to determine the lethal concentration (LC50 value. Following acute test, fish were treated with sub-acute concentrations of CuO-NPs (50 and 70% 96 h-LC50 at with one control group (no CuO-NPs for a week to determine the changes in the level of some plasma hematological and biochemical parameters. Results:The 96 h-LC50 values of CuO-NPs was 2.19±0.003 mg/l. R. rutilus exhibited significantly lower RBC count, Hb and Hct values and a significant increase in the WBC numbers, MCH, MCHC and MCV indices (p

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

Science.gov (United States)

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

2016-11-01

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

Acute toxicity assessment of Osthol content in bio-pesticides using two aquatic organisms

Directory of Open Access Journals (Sweden)

Eun-Chae Yim

2014-12-01

Full Text Available Objectives This study focused on the assessment of acute toxicity caused by Osthol, a major component of environment-friendly biological pesticides, by using two aquatic organisms. Methods The assessment of acute toxicity caused by Osthol was conducted in Daphnia magna and by examining the morphological abnormalities in Danio rerio embryos. Results The median effective concentration value of Osthol in D. magna 48 hours after inoculation was 19.3 μM. The median lethal concentration of D. rerio embryo at 96 hours was 30.6 μM. No observed effect concentration and predicted no effect concentration values of Osthol in D. magna and D. rerio were calculated as 5.4 and 0.19 μM, respectively. There was an increase in the morphological abnormalities in D. rerio embryo due to Osthol over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation were observed in embryos at 24–48 hours. Symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects, and symptoms of collapse were observed in fertilized embryo tissue within 96 hours. Ocular defects and pigmentation were the additional symptoms observed in this study. Conclusions Because Osthol showed considerable toxicity levels continuous toxicity evaluation in agro-ecosystems is necessary when bio-pesticides containing Osthol are used.

Is the OECD acute worm toxicity test environmentally relevant? The effect of mineral form on calculated lead toxicity

International Nuclear Information System (INIS)

Davies, N.A.Nicola A.; Hodson, M.E.Mark E.; Black, S.Stuart

2003-01-01

The current OECD acute worm toxicity test does not relate well to ambient conditions. - In a series of experiments the toxicity of lead to worms in soil was determined following the draft OECD earthworm reproduction toxicity protocol except that lead was added as solid lead nitrate, carbonate and sulphide rather than as lead nitrate solution as would normally be the case. The compounds were added to the test soil to give lead concentrations of 625-12500 μg Pb g -1 of soil. Calculated toxicities of the lead decreased in the order nitrate>carbonate>sulphide, the same order as the decrease in the solubility of the metal compounds used. The 7-day LC 50 (lethal concentration when 50% of the population is killed) for the nitrate was 5321±275 μg Pb g -1 of soil and this did not change with time. The LC 50 values for carbonate and sulphide could not be determined at the concentration ranges used. The only parameter sensitive enough to distinguish the toxicities of the three compounds was cocoon (egg) production. The EC 50 s for cocoon production (the concentration to produce a 50% reduction in cocoon production) were 993, 8604 and 10246 μg Pb g -1 of soil for lead nitrate, carbonate and sulphide, respectively. Standard toxicity tests need to take into account the form in which the contaminant is present in the soil to be of environmental relevance

The acute toxicity of ethanol extract from irradiated Temulawak (curcuma xanthorrizha roxb.) which have anticancer activity

International Nuclear Information System (INIS)

Ermin Katrin; Susanto; Hendig Winarno

2011-01-01

Pasteurization of herbs and herbal medicinal products have been carried out by several herbal industries, but information about the safety of irradiated herbal medicine is still a little, even the influence of gamma irradiation for pasteurization purpose on the toxicity of crude Temulawak has never been investigated. The ethanol extract of Curcuma xanthorrizha Roxb. has cytotoxic activity which potential as an anticancer. In this research, the acute toxicity tests were carried out to the ethanol extract from Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy. The acute toxicity tests of ethanol extract were conducted in mice by observing the effect of extracts on animal behavior (pharmacologic profile) after a single dose of test material, the development of animal body weight and death every day for 14 days and observed several organ weights on day 14. Acute toxicity test results after administration of extracts on male and female mice a dose up to 7500 mg/kg body weight (BW) showed that no deaths and no significant toxic effect, so that the ethanol extract of Curcuma xanthorrizha without irradiation and irradiated with doses of 5 and 10 kGy can be declared safe. Thus LD 50 from ethanol extract of Curcuma xanthorrizha without irradiation and irradiated (5 and 10 kGY) in mice was greater than 7500 mg/kg body weight. (author)

Use of various acute, sublethal and early life-stage tests to evaluate the toxicity of refinery effluents

International Nuclear Information System (INIS)

Sherry, J.; Scott, B.; Dutka, B.

1997-01-01

The toxicities of effluents from three Ontario, Canada, refineries were assessed with microbes, plants, invertebrates, and fish. Acute toxicity was assessed by the Microtox test, an assay based on electron transport activity in submitochondrial particles, and Daphnia magna (water flea); growth of Selenastrum capricornutum (alga); growth of Lemna minor (aquatic plant); germination of Lactuca sativa (nonaquatic plant); survival, growth, and maturation of Panagrellus redivivus (nematode); and genotoxicity in the SOS-Chromotest. Only the Microtox test and the submitochondrial particle test detected acute toxicity in the effluent samples. Reduced survival and sublethal responses were caused by some effluents, but not all effluents were toxic, and none caused a response in all of the tests applied. The results suggest that the effluent treatment systems used at Ontario refineries have largely eliminated acute toxicity to the organisms in their test battery. Although reduced survival and sublethal effects were detected in some of the effluents, the effects were minor. Some of the tests provided evidence, albeit weak, of variations in the responses of the test organisms to a temporal series of effluent samples. Not unexpectedly, there were also minor differences in the responses of the tests to effluents from the three refineries. The fathead minnow test seems to be a sensitive indicator of the sublethal toxicity of Ontario refinery effluents

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

International Nuclear Information System (INIS)

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

1990-01-01

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

A Challenging Case of Acute Mercury Toxicity

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Ali Nayfeh

2018-01-01

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

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

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Swapnil Chavan

2014-10-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Acute toxicity of postoperative IMRT and chemotherapy for endometrial cancer

International Nuclear Information System (INIS)

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

2007-01-01

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

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

DEFF Research Database (Denmark)

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

2018-01-01

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

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

African Journals Online (AJOL)

OKEY

2014-01-29

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

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

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Akram Ghadirkhomi

2016-08-01

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

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

Science.gov (United States)

2012-07-23

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

Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

African Journals Online (AJOL)

fisiologia

2012-09-18

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

Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

Science.gov (United States)

Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

2013-06-01

In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

Copper, but not cadmium, is acutely toxic for trout hepatocytes: short-term effects on energetics and ion homeostasis

International Nuclear Information System (INIS)

Manzl, Claudia; Ebner, Hannes; Koeck, Guenter; Dallinger, Reinhard; Krumschnabel, Gerhard

2003-01-01

The toxic effects of cadmium (Cd) and copper (Cu) on cellular energy metabolism and ion homeostasis were investigated in hepatocytes from the rainbow trout, Oncorhynchus mykiss. The metal content of cells did not increase during incubation with Cu, whereas a dose-dependent increase was seen with Cd. Cell viability was unaffected in the presence of 100 μM Cd and 10 μM Cu but was significantly reduced after 30 min of exposure to 100 μM Cu, both in the presence and absence of extracellular calcium. Oxygen consumption (VO 2 ) was not affected by 100 μM Cd or 10 μM Cu, whereas 100 μM Cu caused a significant and calcium-dependent increase of VO 2 . Lactate production and basal glucose release were not altered by either of the metals. However, the epinephrine-stimulated rate of glucose release was significantly reduced after 2 h of incubation with 100 μM Cu. Hepatocytes exposed to Cd showed only a marginal increase of intracellular free calcium (Ca i 2+ ), whereas with Cu a pronounced and dose-dependent increase of Ca i 2+ was induced after a delay of 10 to 15 min, the calcium being of extracellular origin. Intracellular pH was not altered by Cd but decreased significantly in the presence of Cu. Overall our data demonstrate that Cu, but not Cd, is acutely toxic for trout hepatocytes. Since Cu does not enter the cells in the short term it appears to exert its acutely toxic effects at the cell membrane. Although Cu toxicity is associated with an uptake of calcium from extracellular space, leading to an elevation of cellular respiration, cytotoxicity does not appear to be dependent on the presence of extracellular calcium

Acute and chronic toxic effects of chloramphenicol on Scenedesmus obliquus and Chlorella pyrenoidosa.

Science.gov (United States)

Zhang, Wei; Sun, Wenfang; An, Shuai; Xiong, Bang; Lin, Kuangfei; Cui, Xinhong; Guo, Meijin

2013-08-01

The acute and chronic toxicological effects of Chloramphenicol (CAP) on Scenedesmus obliquus and Chlorella pyrenoidosa are not well understood. The indoor experiments were carried to observe and analyze the CAP induced changes. Results of the observations have showed that CAP exposure could significantly inhibit the growth of Scenedesmus obliquus in almost all the treated groups, while Chlorella pyrenoidosa exhibited less sensitivity. Chlorophyll-a syntheses of Scenedesmus obliquus were all inhibited by CAP exposure, while Chlorella pyrenoidosa displayed obvious stimulation effect. Catalase (CAT) and Superoxide dismutase (SOD) activities of both algae were promoted in all the treatments. The experimental results indicated that the growth and Chlorophyll-a syntheses of Scenedesmus obliquus were more sensitive in response to CAP exposure than that of Chlorella pyrenoidosa. While for CAT and SOD activities, Chlorella pyrenoidosa showed more susceptible. This research provides a basic understanding of CAP toxicity to aquatic organisms.

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

Science.gov (United States)

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

2016-11-01

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

Comparison of Acute Toxicity of Algal Metabolites Using Bioluminescence Inhibition Assay

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Hansa Jeswani

2015-01-01

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

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

Science.gov (United States)

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

Acute toxicity of injection of 153Sm-EDTMP

International Nuclear Information System (INIS)

Chen Baiwei; Chai Xuehong

2004-01-01

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

Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

International Nuclear Information System (INIS)

Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

2008-01-01

Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices

Studies of the ionizing radiation effects on the effluents acute toxicity due to anionic surfactants

International Nuclear Information System (INIS)

Moraes, Maria Cristina Franco de

2004-01-01

Several studies have shown the negative effects of surfactants, as detergents active substance, when discharged on biological sewage wastewater treatment plants. High toxicity may represent a lower efficiency for biological treatment. When surfactants are in aquatic environment they may induce a loss of grease revetment on birds (feather). Depending on the surfactant concentration, several damages to all biotic systems can happen. Looking for an alternative technology for wastewater treatment, efficient for surfactant removal, the present work applied ionizing radiation as an advanced oxidation process for affluents and effluents from Suzano Treatment Station. Such wastewater samples were submitted to radiation using an electron beam from a Dynamic Electron Beam Accelerator from Instituto de Pesquisas Energeticas e Nucleares. In order to assess this proposed treatment efficacy, it was performed acute toxicity evaluation with two test-organisms, the crustacean Daphnia similis and the luminescent bacteria Vibrio fischeri. The studied effluents were: one from a chemical industry (IND), three from sewage plant (affluents - GG, GM and Guaio) and the last biologically treated secondary effluent (EfF), discharged at Tiete river. The applied radiation doses varied from 3 kGy to 50 kGy, being 50 kGy enough for surfactant degradation contained at industrial effluent. For GG, GM and Guaio samples, doses of 6 kGy and 10 kGy were efficient for surfactant and toxicity reduction, representing an average removal that varied from 71.80% to 82.76% and toxicity from 30% to 91% for most the effluents. The final effluent was less toxic than the others and the radiation induced an average 11% removal for anionic surfactant. The industrial effluents were also submitted to an aeration process in order to quantify the contribution of surfactant to the whole sample toxicity, once it was partially removed as foam and several fractions were evaluated for toxicity. (author)

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

African Journals Online (AJOL)

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

Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer

International Nuclear Information System (INIS)

Peeters, Stephanie T.H.; Hoogeman, Mischa S.; Heemsbergen, Wilma D.; Slot, Annerie; Tabak, Hans; Koper, Peter C.M.; Lebesque, Joos V.

2005-01-01

Purpose: To identify dosimetric variables predictive of acute gastrointestinal (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy (HT) is independently associated with acute GI and GU toxicity in prostate cancer patients treated with conformal radiotherapy (RT). Methods and Materials: This analysis was performed on 336 patients participating in a multicenter (four hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume consisted of the prostate with or without the seminal vesicles, depending on the risk of seminal vesicle involvement. The margin from the clinical target volume to the planning target volume was 1 cm. For these patients, the treatment plan for a total dose of 68 Gy was used, because nearly all toxicity appeared before the onset of the 10-Gy boost. Acute toxicity ( 3 months before RT). Results: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients. Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT (50%). The volumes of the prostate and seminal vesicles were significantly smaller in both groups receiving neoadjuvant HT compared with those receiving no HT. In multivariate logistic regression analysis, including the two statistically significant clinical variables neoadjuvant HT and hospital, a volume effect was found for the relative, as well as absolute, rectal wall volumes exposed to intermediate and high doses. Of all the length parameters, the relative rectal length irradiated to doses of ≥5 Gy and ≥30 Gy and absolute lengths receiving ≥5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or worse was reported in 56% of cases. For patients with pretreatment GU symptoms, the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate analysis, containing the variables

Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

Science.gov (United States)

Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

2008-01-01

The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

Evaluation of acute toxicity of babassu mesocarp in mice

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Elizabeth S. B. Barroqueiro

2011-07-01

Full Text Available The safety of babassu mesocarp (Orbignya phalerata Mart., Arecaceae, which exhibited anti-inflammatory and antithrombotic activities, was evaluated by determining the potential acute toxicity in mice. A lyophilized ethanol extract of babassu mesocarp (BME was administered to C3H/HePas mice (10/group in a single dose of 1000, 3000 and 5000 mg/kg, by gavage. General behavior adverse effects and mortality were determined for up to fourteen days. Selected biochemical parameters including glucose, triacylglyceride, cholesterol, urea, alkaline phosphatase and creatinine were determined by colorimetric assay. The heart, liver, spleen, kidneys and brain were weighted and evaluated macro and microscopically. The median lethal dose (LD50 of BME was greater than 5000 mg/kg. No behavior or body weight alterations were detected after the treatment. The acute treatment with BME has no effect on macroscopic and microscopic aspect of examined organs. Instead, BME increased the alkaline phosphatase and reduced the urea concentration in all groups. A significant increase on triacylglyceride was detected in the group BME1000. In conclusion, the acute treatment with high doses of BME can affect some biochemical parameters with a long lasting effect, although any change was detected at tissue level or body and organ weight.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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

African Journals Online (AJOL)

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

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

DEFF Research Database (Denmark)

Da Silva, Emilie; Sørli, Jorid Birkelund

2018-01-01

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

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

Directory of Open Access Journals (Sweden)

Yalena Prado

2015-02-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-15

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

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

African Journals Online (AJOL)

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

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

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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.

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

African Journals Online (AJOL)

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

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

Science.gov (United States)

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

2017-04-01

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

Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

Science.gov (United States)

Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

2008-05-01

Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

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

Directory of Open Access Journals (Sweden)

Ramaswamy Ramaswamy

2012-10-01

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

Cumulative toxicity of neonicotinoid insecticide mixtures to Chironomus dilutus under acute exposure scenarios.

Science.gov (United States)

Maloney, Erin M; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-11-01

Extensive agricultural use of neonicotinoid insecticide products has resulted in the presence of neonicotinoid mixtures in surface waters worldwide. Although many aquatic insect species are known to be sensitive to neonicotinoids, the impact of neonicotinoid mixtures is poorly understood. In the present study, the cumulative toxicities of binary and ternary mixtures of select neonicotinoids (imidacloprid, clothianidin, and thiamethoxam) were characterized under acute (96-h) exposure scenarios using the larval midge Chironomus dilutus as a representative aquatic insect species. Using the MIXTOX approach, predictive parametric models were fitted and statistically compared with observed toxicity in subsequent mixture tests. Single-compound toxicity tests yielded median lethal concentration (LC50) values of 4.63, 5.93, and 55.34 μg/L for imidacloprid, clothianidin, and thiamethoxam, respectively. Because of the similar modes of action of neonicotinoids, concentration-additive cumulative mixture toxicity was the predicted model. However, we found that imidacloprid-clothianidin mixtures demonstrated response-additive dose-level-dependent synergism, clothianidin-thiamethoxam mixtures demonstrated concentration-additive synergism, and imidacloprid-thiamethoxam mixtures demonstrated response-additive dose-ratio-dependent synergism, with toxicity shifting from antagonism to synergism as the relative concentration of thiamethoxam increased. Imidacloprid-clothianidin-thiamethoxam ternary mixtures demonstrated response-additive synergism. These results indicate that, under acute exposure scenarios, the toxicity of neonicotinoid mixtures to C. dilutus cannot be predicted using the common assumption of additive joint activity. Indeed, the overarching trend of synergistic deviation emphasizes the need for further research into the ecotoxicological effects of neonicotinoid insecticide mixtures in field settings, the development of better toxicity models for neonicotinoid mixture

40 CFR 799.9130 - TSCA acute inhalation toxicity.

Science.gov (United States)

2010-07-01

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

Phytochemical composition and acute toxicity evaluation of aqueous ...

African Journals Online (AJOL)

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

Toxicity levels to humans during acute exposure to hydrogen fluoride

International Nuclear Information System (INIS)

Halton, D.M.; Dranitsaris, P.; Baynes, C.J.

1984-11-01

A literature review was conducted of the acute toxicity of hydrogen fluoride (HF) with emphasis on the effects of inhalation of gaseous HF. The data and findings of the relevant references were summarized under four categories: animal studies, controlled human studies, community exposure and industrial exposure. These were critically reviewed and then lethal concentration-time relationships were developed for humans, corresponding to LCsub(LO), LCsub(10) and LCsub(50) levels. The effects of age, health and other physiological variables on the sensitivity to HF were discussed, as well as antagonistic and synergistic effects with other substances

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

DEFF Research Database (Denmark)

Sanderson, Hans; Thomsen, Marianne

2009-01-01

data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

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

International Nuclear Information System (INIS)

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

2011-01-01

The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L -1 , 2.34 mg.L -1 , 2.35 mg.L -1 and 1.80 mg.L -1 , respectively, showing a notable reduction of the acute toxicity for this organism. (author)

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Toxic effects of formalin-treated cadaver on medical students, staff ...

African Journals Online (AJOL)

Background: Formaldehyde can be toxic, allergenic and carcinogenic. Evaporation of formaldehyde from formalin-treated cadavers in the anatomy dissection rooms can produce high exposure. This study was conducted to assess acute and chronic toxic effects of formalin-treated cadavers on medical students, staff ...

Acute toxicity of birch tar oil on aquatic organisms

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M. HAGNER

2008-12-01

Full Text Available Birch tar oil (BTO is a by-product of processing birch wood in a pyrolysis system. Accumulating evidence suggests the suitability of BTO as a biocide or repellent in terrestrial environments for the control of weeds, insects, molluscs and rodents. Once applied as biocide, BTO may end up, either through run-off or leaching, in aquatic systems and may have adverse effects on non-target organisms. As very little is known about the toxicity of BTO to aquatic organisms, the present study investigated acute toxicity (LC50/EC50 of BTO for eight aquatic organisms. Bioassays with the Asellus aquaticus (crustacean, Lumbriculus variegatus (oligochaeta worm, Daphnia magna (crustacean, Lymnea sp. (mollusc, Lemna minor (vascular plant, Danio rerio (fish, Scenedesmus gracilis (algae, and Vibrio fischeri (bacterium were performed according to ISO, OECD or USEPA-guidelines. The results indicated that BTO was practically nontoxic to most aquatic organisms as the median effective BTO concentrations against most organisms were >150 mg L-1. In conclusion, our toxicity tests showed that aquatic organisms are to some extent, invariably sensitive to birch tar oil, but suggest that BTO does not pose a severe hazard to aquatic biota. We deduce that, unless BTOs are not applied in the immediate vicinity of water bodies, no special precaution is required.;

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-05-01

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

Analysis of acute and late toxicity of adjuvant radiotherapy in women with cervical and endometrial cancer

International Nuclear Information System (INIS)

Warenczak-Florczak, Z.; Roszak, A.; Wlodarczyk, H.; Wojciechowska-Lacka, A.

2011-01-01

Background: In case of pure prognostic factors women with cervical and endometrial cancer after surgical operation need to be treated with radiotherapy . Every radiation treatment may be involved with toxicity, acute and late. Material and methods: Performed was detailed analysis of 173 patients with cervical (38) and endometrial (135) cancer. We evaluated early and late post radiation reactions in all patients. Results: Acute reactions were found in 48.5% and late toxicity was found in 9.8% of patients. Women with endometrial cancer were significantly older then patients with cervical cancer (p < 0.002). Higher percentage of acute and late toxicity was observed from the bowel tah urinary tract (26% and 22.5% - acute; 8.1% and 1.73% - late). Higher percentage of acute side effects was observed in patients with cervical than with endometrial cancer (60.5% and 33.7%). Late post radiation reaction predominate also in patient with cervical cancer (13.2% and 8.9%). The adverse effects were associated with prolonged time of treatment due to breaks in radiotherapy. Higher percentage of breaks was found in older patients, more frequent in patient with endometrial than in cervical cancer group (7.4% and 2.6%).To conclude early postradiation reaction appeared more frequently, than late post radiation reactions. It was stated that early and late post radiation reaction appear more frequently in women with cervical than in endometrial cancer. Interruption in radiation delivery was longer than seven days in group with endometrial cancer that leads to extension of complete radiation treatment. (authors)

Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

Science.gov (United States)

Johnson, W. Waynon; Finley, Mack T.

1980-01-01

Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

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

Directory of Open Access Journals (Sweden)

Petra Doleželová

2011-01-01

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

Comparative acute toxicity of neonicotinoid and pyrethroid insecticides to non-target crayfish (Procambarus clarkii) associated with rice-crayfish crop rotations.

Science.gov (United States)

Barbee, Gary C; Stout, Michael J

2009-11-01

Most insecticides used to control rice water weevil (Lissorhoptrus oryzophilus Kuscel) infestations are pyrethroids. However, pyrethroids are highly toxic to non-target crayfish associated with rice-crayfish crop rotations. One solution to the near-exclusive reliance on pyrethroids in a rice-crayfish pest management program is to incorporate neonicotinoid insecticides, which are insect specific and effective against weevils but not extremely toxic to crayfish. This study aimed to take the first step to assess neonicotinoids as alternatives to pyrethroids in rice-crayfish crop rotations by measuring the acute toxicities of three candidate neonicotinoid insecticides, clothianidin, dinotefuran and thiamethoxam, to juvenile Procambarus clarkii (Girard) crayfish and comparing them with the acute toxicities of two currently used pyrethroid insecticides, lambda-cyhalothrin and etofenprox. Neonicotinoid insecticides are at least 2-3 orders of magnitude less acutely toxic (96 h LC(50)) than pyrethroids to juvenile Procambarid crayfish: lambda-cyhalothrin (0.16 microg AI L(-1)) = etofenprox (0.29 microg AI L(-1)) > clothianidin (59 microg AI L(-1)) > thiamethoxam (967 microg AI L(-1)) > dinotefuran (2032 microg AI L(-1)). Neonicotinoid insecticides appear to be much less hazardous alternatives to pyrethroids in rice-crayfish crop rotations. Further field-level neonicotinoid acute and chronic toxicity testing with crayfish is needed. (c) 2009 Society of Chemical Industry.

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

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Gérard A. Toudji

2017-10-01

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

Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

International Nuclear Information System (INIS)

Ferrigno, Robson; Santos, Adriana; Martins, Lidiane C; Weltman, Eduardo; Chen, Michael J; Sakuraba, Roberto; Lopes, Cleverson P; Cruz, José C

2010-01-01

This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups

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

Science.gov (United States)

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

2018-05-15

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

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

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Patel Ajaykumar B

2012-02-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

[Acute onset pulmonary toxicity associated to amiodarone].

Science.gov (United States)

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

2012-01-01

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

Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

Science.gov (United States)

Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

2012-11-01

The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

Science.gov (United States)

Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

2014-09-01

Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

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

Science.gov (United States)

Sanderson, Hans; Thomsen, Marianne

2009-06-01

Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68% of the pharmaceuticals have a non-specific MOA. Additionally, the acute-to-chronic ratio (ACR) for 70% of the analyzed pharmaceuticals was below 25 further suggesting a non-specific MOA. Sub-lethal receptor-mediated effects may however have a more specific MOA.

Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

Science.gov (United States)

Popov, Dmitri; Maliev, Slava

. Radiation Toxins (SRD-1)had been isolated from Central Lymph of irradiated animals (cows, sheep, pigs). Experiments to study toxicity of Radiation Neurotoxins had been performed. Intravenous (IV) and intramuscular (IM) administration of RT SRD-1 to radiation naive animals had induced acute toxicity which referred to the harmful effects generated by high doses of radiation. In-jection of toxic doses of RT SRD-1 (Toxic doses: 0,1 mg/kg, 0,5mg/kg, 1 mg/kg, 10mg/kg,30 mg/kg, 50mg/kg,70 mg/kg,100 mg/kg, 110mg/kg)were compared to the similar effects caused by high doses of radiation. Results: Injection of SRD-1 ( Neurotoxin Cv ARS)of all ten tested toxic doses had caused a death of radiation naive animals within the first hours after admin-istration of toxins. For all animals in all experiments, a short period of extreme agitation was replaced by deep coma, and suppression of blood circulation and breathing. The results of postmortem section had showed characteristics of intra-cortical hemorrhage. Conclusions: Acute radiation injury induces a disorder of blood supply of the Central Nervous System (CNS). However, administration of SRD-1 Radiation Toxins to radiation naive animals produces crit-ically important inflammatory reactions with hemorrhagic stroke development. Neurotoxicity and Excitotoxicity are two stages of the pathological processes resulted in damaging and killing nerve cells thorough apoptotic necrosis. Excitotoxicity is well known as a pathological process that occurs when important excitatory neurotransmitters (glutamate, serotonin) over-activate the receptors -NMDA, AMPA, 5HT1, 5HT2, 5H3. Radiation Neurotoxins possibly act on the same receptors and activate the cell death mechanisms through direct or indirect excessive activation of same receptors.

AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

Science.gov (United States)

The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

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

Data.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Idania Rodeiro

2018-02-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Santos, Dymes R.A.; Garcia, Vanessa S.G.; Vilarrubia, Anna C.S.; Borrely, Sueli I., E-mail: vanessagarcia@usp.br, E-mail: sborrely@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

The constant use of pharmaceutical drugs by great part of the population and its continuous input into the environment creates a growing need of investigating its presence, behavior and the effects on aquatic biota, as well as new ways to treat wastewater containing such substances. The fluoxetine hydrochloride (FH) present in the drug Prozac is an active ingredient used in the treatment of depressive and anxiety disorders. Generally, these compounds enter the aquatic environment by sewage collectors systems after undergoing prior treatment in sewage treatment plants (STPs) or without any treatment. This study focused on evaluating the reduction of acute toxicity of the pharmaceutical FH, under its manipulated formula, for the marine bacterium Vibrio fischeri. It was also evaluated the acute toxicity of the aqueous solution containing the FH after its exposition to ionizing radiation from industrial electron accelerator. It was performed acute toxicity tests lasting 15 minutes, where the average EC (50) of the non-irradiated CF water solution was approximately 0.68 mg L-1. While the CF water solution irradiated with 1 kGy, 2.5 kGy, 7.5 kGy and 10 kGy, presented an average EC(50) 1.63 mg.L{sup -1}, 2.34 mg.L{sup -1}, 2.35 mg.L{sup -1} and 1.80 mg.L{sup -1}, respectively, showing a notable reduction of the acute toxicity for this organism. (author)

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

Directory of Open Access Journals (Sweden)

S. O. El Okle

2014-09-01

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

Methotrexate-induced acute toxic leukoencephalopathy

Directory of Open Access Journals (Sweden)

Parag R Salkade

2012-01-01

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

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

Science.gov (United States)

Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Asparaginase-Associated toxicity in children with acute lymphoblastic leukemia

NARCIS (Netherlands)

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

2016-01-01

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

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

Science.gov (United States)

Wei, Li; Shao, Wei-Wei; Ding, Guo-Hua; Fan, Xiao-Li; Yu, Miao-Ling; Lin, Zhi-Hua

2014-07-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

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

Science.gov (United States)

Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

2012-07-01

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

A proposal of classification for acute toxicity; Una scala di tossicita`

Energy Technology Data Exchange (ETDEWEB)

Oddo, N. [Ecotox srl, Pregnana Milanese (Italy)

1998-05-01

A classification for acute toxicity is proposed, including the effects to low level exposures (Hormesis). The criteria, the measurement units and the correlations to chronic and to genotoxicity of the proposed classification are discussed. [Italiano] Viene proposta una scala per la tossicita` acuta, comprendendovi gli effetti deboli (Ormesi). Vengono discussi i criteri di formulazione della scala, le unita` di misura adottate, e le relazioni con la tossicita` cronica e con la genotossicita`.

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

OpenAIRE

Adam D. Wilkinson; Catherine J. Collier; Florita Flores; Andrew P. Negri

2015-01-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ...

Acute toxicity tests with Daphnia magna, Americamysis bahia, Chironomus riparius and Gammarus pulex and implications of new EU requirenments for the aquatic effect assessment of insecticides

NARCIS (Netherlands)

Brock, T.C.M.; Wijngaarden, van R.P.A.

2012-01-01

Threshold concentrations for treatment related effects of 31 insecticides, as derived from aquatic micro-/mesocosm tests, were used to calibrate the predictive value of the European Tier-1 acute effect assessment on basis of laboratory toxicity tests with Daphnia magna, Chironomus spp., Americamysis

Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

Energy Technology Data Exchange (ETDEWEB)

Amsbaugh, Mark J. [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Grosshans, David R., E-mail: dgrossha@mdanderson.org [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2012-08-01

Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

International Nuclear Information System (INIS)

Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

2010-01-01

Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R 2 , 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

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

Science.gov (United States)

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

2015-03-15

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-03-15

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

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

Science.gov (United States)

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

Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

International Nuclear Information System (INIS)

Halton, D.M.

1995-09-01

In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC LO , LC 10 and LC 50 levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs

Toxicity levels to humans during acute exposure to hydrogen fluoride - An update

Energy Technology Data Exchange (ETDEWEB)

Halton, D M

1995-09-01

In March 1993, the Atomic Energy Control Board (AECB) commissioned and update of a 1984 review on the acute toxicity of hydrogen fluoride (HF). The study places particular emphasis on the effects of inhalation of gaseous HF and is divided into two main parts: a literature review and a lethal concentration (LC) estimation. The literature review summarizes data under four categories: animal studies, controlled human studies, community exposure, and industrial exposure. Data in these areas were critically reviewed for their relevance to lethal concentrations at LC{sub LO}, LC{sub 10} and LC{sub 50} levels that were derived in the 1984 report. In the last ten years, only one relevant animal study has been published. No new controlled human studies were found but a community exposure incident was reported. There were three new industrial/accidental exposures reported since 1984. Evaluation of new data does not change the lethal concentration estimates made in the 1984 report, but does indicate the absence of appropriate models to estimate the lethality of irritant and corrosive gases. In the last 10 years, much literature on the evaluation of major hazards has been published and suggests that such assessments are of growing political, economic and social importance. Numerous articles have been published on the acute toxicity of HF from skin contact and chronic toxicity from repeated airborne exposure. These publications offer important insights into the nature of HF toxicity. Several avenues of investigative research are suggested. (author). 55 refs., 4 tabs.

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

African Journals Online (AJOL)

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

Development of a standard acute dietary toxicity test for the silkworm (Bombyx mori L.)

NARCIS (Netherlands)

Sun, X.; Valk, H.; Jiang, H.; Wang, X.; Yuan, S.; Zhang, Y.; Roessink, I.; Gao, X.

2012-01-01

Larvae of the silkworm (Bombyx mod L.) may be exposed to pesticide residues on the leaves of their food plant, the mulberry tree (Morus spp.), which can lead to adverse effects on silk production. A new acute dietary toxicity test method was evaluated as the basis for pesticide risk assessment. A

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

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Letícia Flohr

2012-01-01

Full Text Available Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3 induced the highest toxicity level to Daphnia magna(CE50,48 h=2.21%. A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min=12.08%. All samples of pulp and paper wastes, and a textile waste (sample TX2 induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: Feasibility and acute toxicity

International Nuclear Information System (INIS)

Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean Marc; Lefloch, Olivier; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdin, Sylvain; Bachaud, Jean Marc; Maingon, Philippe; Lagrange, Jean-L.eon; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal M.D.; Hay, Men H.; Dubray, Bernard; Luporsi, Elisabeth; Bey, Pierre

2004-01-01

Purpose: To describe treatments and acute tolerance in a randomized trial comparing 70 Gy and 80 Gy to the prostate in patients with localized prostate cancer. Methods and materials: Between September 1999 and February 2002, 306 patients were randomized to receive 70 Gy (153 patients) or 80 Gy (153 patients) in 17 institutions. Patients exhibited intermediate-prognosis tumors. If the risk of node involvement was greater than 10%, surgical staging was required. Previous prostatectomy was excluded, and androgen deprivation was not admitted. The treatment was delivered in two steps. PTV1-including seminal vesicles, prostate, and a 1-0.5-cm margin-received 46 Gy given with a 4-field conformal technique. PTV2, reduced to prostate with the same margins, irradiated with at least 5 fields. Dose was prescribed according to ICRU recommendations in the 70 Gy group, but adapted at the 80 Gy level. Results: All patients but one in the 80 Gy arm completed the treatment. In the 70 Gy arm, the mean dose to the PTV2 was 69.5 Gy. In the 80 Gy arm, the mean dose in the PTV2 was 78.5 Gy. Acute toxicity according to Radiation Therapy Oncology Group scale during treatment was reported in 306 patients. There was no statistically significant difference between the two arms: 12% had no toxicity, 80% complained of bladder toxicity, and 70% complained of rectal symptoms. Two months after the end of treatment, 43% of the 70 Gy level and 48% of the 80 Gy level complained of side effects, including 24% and 20% of sexual disorders. There was 6% and 2% of Grade 3 urinary and rectal toxicity. Five patients required a 10-29-day suspension of the treatment. Acute Grade 2 and 3 side effects were related to PTV and CTV1 size, which was the only independent predictive factor in multivariate analysis. Toxicity was not related to the center, age, arm of treatment, or selected data from dose-volume histogram of organ at risk. Conclusion: Treatments were completed in respect to constraints. Acute toxicity

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

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Mustak Sayyad

2017-02-01

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

Moist skin care can diminish acute radiation-induced skin toxicity

International Nuclear Information System (INIS)

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

2003-01-01

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

Acute toxicity assessment of camphor in biopesticides by using and

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Eun-Chae Yim

2014-09-01

Full Text Available Objectives An ecofriendly alternative to chemical pesticides is bio-pesticides, which are derived from natural sources. The interest in bio-pesticides is based on the disadvantages associated with chemical pesticides. Methods We conducted acute toxicity assessments of camphor, a major component of bio-pesticides, by using Daphnia magna (D. magna as well as assessed the morphological abnormalities that occurred in Danio rerio (D. rerio embryos. Results The median effective concentration of camphor on D. magna after 48 hours was 395.0 μM, and the median lethal concentration on D. rerio embryos after 96 hours was 838.6 μM. The no observed effect concentration and predicted no effect concentration of camphor on D. magna, which was more sensitive than D. rerio, were calculated as 55.2 μM and 3.95 μM, respectively. Morphological abnormalities in D. rerio embryos exposed to camphor increased over time. Coagulation, delayed hatching, yolk sac edema, pericardial edema, and pigmentation of embryos mainly appeared between 24 and 48 hours. Further, symptoms of scoliosis and head edema occurred after 72 hours. In addition, bent tails, ocular defects and collapsed symptoms of fertilized embryonic tissue were observed after 96 hours. Conclusions The camphor toxicity results suggest that continuous observations on the ecosystem are necessary to monitor toxicity in areas where biological pesticides containing camphor are sprayed.

Acute and chronic toxicity and antimicrobial activity of the extract of Stryphnodendron adstringens (Mart. Coville

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Anna C. Almeida

Full Text Available ABSTRACT: This study evaluated the antimicrobial activity and acute or chronic toxicity of the extract of Stryphnodendron adstringens. The stem bark dry extract was obtained by static maceration with ethanol. Quantification of tannins was performed by the Folin-Denis method, which indicated a total tannin content of 32.7%. The antimicrobial activity of the dry extract of S. adstringens was evaluated by agar-based disk diffusion assay with Escherichia coli (ATCC 25922 and Staphylococcus aureus (ATCC 25923 in the concentration of 200, 400 and 600μL/mL. The results indicated that 600μL/mL inhibited microbial growth, i.e. had antimicrobial activity against these species. Acute and chronic toxic effects of S. adstringens was evaluated in Wistar rats treated with 200, 400, 600 and 800mg/kg of extract, administrated by gavage. Liver degeneration was observed in the group of rats receiving 800mg/kg in chronic exposure, what may indicate some degree of toxicity at this concentration. However, no systemic toxicity was observed at lower doses. Considering the broad use of S. adstringens as a phytotherapeutic agent for various human and animal diseases and the livertoxicity observed at high concentrations, attention should be paid to the possible adverse effect of using the extract from this plant at high concentration.

Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

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Marcella L.B. Carneiro

2015-01-01

Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

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

Czech Academy of Sciences Publication Activity Database

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

2009-01-01

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

Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

Science.gov (United States)

Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

2015-04-01

Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

The acute toxicity of the metaldehyde on the climbing perch

Science.gov (United States)

Wahida Mohamad Ismail, Syamimi; Aini Dahalan, Farrah; Zakaria, Ammar; Mad Shakaff, Ali Yeon; Aqlima Ahmad, Siti; Shukor, Mohd Yunus Abd; Khalizan Sabullah, Mohd; Khalil, Khalilah Abdul; Jalil, Mohd Faizal Ab

2018-03-01

In Asia, Climbing perch (Anabas testudineus) is commonly found in paddy fields and irrigation systems. Due to its habitat, Climbing perch is exposed to toxic pesticides used in paddy fields such as metaldehyde which is one of the most widely used molluscicide. This study aims to determine the acute toxicity Lethal Concentration50 (LC50) of metaldehyde and its effect on the behaviour and physical changes of the Climbing perch. The fish mortality responses to six different metaldehyde concentrations ranging from 180 to 330 mg/L were investigated. The 96-h LC50 values were determined and analysed using three different analysis methods which is arithmetic, logarithmic and probit graphic. The LC50 values obtained in this study were 239, 234 and 232 mg/L, respectively. After 96-h of exposure to metaldehyde, the fish showed a series of abnormal behavioural response in all cases: imbalance position, and restlessness of movement. The LC50 values show that metaldehyde is moderately toxic to the Climbing perch indicating that metaldehyde is not destructive to Climbing perch. However, long term exposure of aquatic organisms to the metaldehyde means a continuous health risk for the fish population as they are more vulnerable and it is on high risk for human to consume this toxicated fishes.

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

Energy Technology Data Exchange (ETDEWEB)

Kasprzak, Kazimierz S. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Diwan, Bhalchandra A. [Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Kaczmarek, Monika Z. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Logsdon, Daniel L. [Laboratory Animal Sciences Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Fivash, Mathew J. [Data Management Services, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Salnikow, Konstantin, E-mail: salnikok@mail.nih.gov [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States)

2011-11-15

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- < gamma > -lactone oxidase gene knock-out mice (Gulo-/- mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni{sub 3}S{sub 2}), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo-/- and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni{sub 3}S{sub 2} carcinogenesis: Gulo-/- mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo-/- mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni{sub 3}S{sub 2}. Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni{sub 3}S{sub 2} in Gulo-/- mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo-/- mice more susceptible to Ni{sub 3}S{sub 2} carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni{sub 3}S{sub 2} and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: Black-Right-Pointing-Pointer Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. Black-Right-Pointing-Pointer Gulo-/- mice unable to synthesize ascorbate were used in this study. Black

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

International Nuclear Information System (INIS)

Kasprzak, Kazimierz S.; Diwan, Bhalchandra A.; Kaczmarek, Monika Z.; Logsdon, Daniel L.; Fivash, Mathew J.; Salnikow, Konstantin

2011-01-01

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- -lactone oxidase gene knock-out mice (Gulo−/− mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni 3 S 2 ), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo−/− and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni 3 S 2 carcinogenesis: Gulo−/− mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo−/− mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni 3 S 2 . Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni 3 S 2 in Gulo−/− mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo−/− mice more susceptible to Ni 3 S 2 carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni 3 S 2 and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: ► Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. ► Gulo−/− mice unable to synthesize ascorbate were used in this study. ► The reduction in ascorbate levels in Gulo−/− mice increased acute toxicity induced by Ni 3 S 2 . �

Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

2012-04-01

Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

2012-01-01

Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Gregers, J; Gréen, H; Christensen, I J

2015-01-01

The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those e...

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

African Journals Online (AJOL)

STORAGESEVER

2008-07-18

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

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

African Journals Online (AJOL)

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

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

African Journals Online (AJOL)

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

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

DEFF Research Database (Denmark)

Sanderson, Hans; Thomsen, Marianne

2009-01-01

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

Effects of Treatment Intensification on Acute Local Toxicity During Radiotherapy for Head and Neck Cancer: Prospective Observational Study Validating CTCAE, Version 3.0, Scoring System

International Nuclear Information System (INIS)

Palazzi, Mauro; Tomatis, Stefano; Orlandi, Ester; Guzzo, Marco; Sangalli, Claudia; Potepan, Paolo; Fantini, Simona; Bergamini, Cristiana; Gavazzi, Cecilia; Licitra, Lisa; Scaramellini, Gabriele; Cantu', Giulio; Olmi, Patrizia

2008-01-01

Purpose: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. Methods and Materials: Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventional fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. Results: Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the 'low-burden' class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the 'high-burden' class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. Conclusions: The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant

Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san

Directory of Open Access Journals (Sweden)

Hwayong Park

2017-06-01

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

Comparison of toxicity of acute overdoses with citalopram and escitalopram.

Science.gov (United States)

Hayes, Bryan D; Klein-Schwartz, Wendy; Clark, Richard F; Muller, Allison A; Miloradovich, Jane E

2010-07-01

Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002-2005. There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68-70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p escitalopram (p = 0.011). In children escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs. Copyright 2010 Elsevier Inc. All rights reserved.

The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.

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Brown, Alastair; Thatje, Sven; Hauton, Chris

2017-09-05

Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.

Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats.

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Christapher, Parayil Varghese; Parasuraman, Subramani; Asmawi, Mohd Zaini; Murugaiyah, Vikneswaran

2017-06-01

Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg. Copyright © 2017 Elsevier Inc. All rights reserved.

N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells.

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Ramesh B Badisa

Full Text Available Cocaine has a short half-life of only about an hour but its effects, predominantly on the central nervous system (CNS, are fairly long-lasting. Of all cells within the CNS, astrocytes may be the first to display cocaine toxicity owing to their relative abundance in the brain. Cocaine entry could trigger several early response changes that adversely affect their survival, and inhibiting these changes could conversely increase their rate of survival. In order to identify these changes and the minimal concentrations of cocaine that can elicit them in vitro, rat C6 astroglia-like cells were treated with cocaine (2-4 mM for 1h and assayed for alterations in gross cell morphology, cytoplasmic vacuolation, viability, reactive oxygen species (ROS generation, glutathione (GSH levels, cell membrane integrity, F-actin cytoskeleton, and histone methylation. We report here that all of the above identified features are significantly altered by cocaine, and may collectively represent the key pathology underlying acute toxicity-mediated death of astroglia-like cells. Pretreatment of the cells with the clinically available antioxidant N-acetyl cysteine (NAC, 5 mM for 30 min inhibited these changes during subsequent application of cocaine and mitigated cocaine-induced toxicity. Despite repeated cocaine exposure, NAC pretreated cells remained highly viable and post NAC treatment also increased viability of cocaine treated cells to a smaller yet significant level. We show further that this alleviation by NAC is mediated through an increase in GSH levels in the cells. These findings, coupled with the fact that astrocytes maintain neuronal integrity, suggest that compounds which target and mitigate these early toxic changes in astrocytes could have a potentially broad therapeutic role in cocaine-induced CNS damage.

A toxicity reduction evaluation for an oily waste treatment plant exhibiting episodic effluent toxicity.

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Erten-Unal, M; Gelderloos, A B; Hughes, J S

1998-07-30

A Toxicity Reduction Evaluation (TRE) was conducted on the oily wastewater treatment plant (Plant) at a Naval Fuel Depot. The Plant treats ship and ballast wastes, berm water from fuel storage areas and wastes generated in the fuel reclamation plant utilizing physical/chemical treatment processes. In the first period of the project (Period I), the TRE included chemical characterization of the plant wastewaters, monitoring the final effluent for acute toxicity and a thorough evaluation of each treatment process and Plant operating procedures. Toxicity Identification Evaluation (TIE) procedures were performed as part of the overall TRE to characterize and identify possible sources of toxicity. Several difficulties were encountered because the effluent was saline, test organisms were marine species and toxicity was sporadic and unpredictable. The treatability approach utilizing enhancements, improved housekeeping, and operational changes produced substantial reductions in the acute toxicity of the final effluent. In the second period (Period II), additional acute toxicity testing and chemical characterization were performed through the Plant to assess the long-term effects of major unit process improvements for the removal of toxicity. The TIE procedures were also modified for saline wastewaters to focus on suspected class of toxicants such as surfactants. The TRE was successful in reducing acute toxicity of the final effluent through process improvements and operational modifications. The results indicated that the cause of toxicity was most likely due to combination of pollutants (matrix effect) rather than a single pollutant.

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

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

2017-08-01

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

Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

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Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

2014-01-01

The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

Identifying and designing chemicals with minimal acute aquatic toxicity.

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

2015-05-19

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

Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests

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Débora Rebechi

2014-09-01

Full Text Available Low malathion concentrations influence metabolism in Chironomus sancticaroli (Diptera, Chironomidae in acute and chronic toxicity tests. Organophosphate compounds are used in agro-systems, and in programs to control pathogen vectors. Because they are continuously applied, organophosphates often reach water sources and may have an impact on aquatic life. The effects of acute and chronic exposure to the organophosphate insecticide malathion on the midge Chironomus sancticaroli are evaluated. To that end, three biochemical biomarkers, acetylcholinesterase (AChE, alpha (EST-α and beta (EST-β esterase were used. Acute bioassays with five concentrations of malathion, and chronic bioassays with two concentrations of malathion were carried out. In the acute exposure test, AChE, EST-α and EST-β activities declined by 66, 40 and 37%, respectively, at 0.251 µg L-1 and more than 80% at 1.37, 1.96 and 2.51 µg L-1. In chronic exposure tests, AChE and EST-α activities declined by 28 and 15% at 0.251 µg L-1. Results of the present study show that low concentrations of malathion can influence larval metabolism, indicating high toxicity for Chironomus sancticaroli and environmental risk associated with the use of organophosphates.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

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

2016-08-18

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

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

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Talib Hussain

2012-04-01

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

Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

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Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

2010-06-01

Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

Stereotactic radiotherapy of meningiomas. Symptomatology, acute and late toxicity

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Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R. [Dept. of Radiation Oncology, Univ. of Gisssen (Germany); Dept. of Radiation Oncology, Marburg Univ. (Germany); Hamm, K.; Surber, G.; Kleinert, G. [Dept. of Stereotactic Neurosurgery and Radiosurgery, Helios Klinikum Erfurt (Germany)

2006-07-15

Background and purpose: stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. Patients and methods: between 1997-2003, 224 patients were treated with SRT (n= 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. Results: the median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III ) was rarely seen (2.5%). Clinically significant late morbidity (III -IV ) or new cranial nerve palsies did not occur. Conclusion: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended. (orig.)

Acute mucocutaneous and systemic adverse effects of Etretinate

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"Mortazavi H

2003-06-01

Full Text Available This cross sectional study was carried out between 1993 to 1998 at Razi Skin Hospital, the affiliated Dermatology Department of Tehran University of Medical Sciences. Eight hundred patients receiving etretinate for various skin diseases took part in this study. Among them, 457 patients with first admission to dermatologic clinic who had at least four regular sequential visits and responding to our questionnaire were selected to enter the study for evaluating acute toxicity of etretinate. Cheilitis with a frequency of 88 percent was the most frequent side effect. Hair loss (22.97%, dry mouth with thirst (15.09%, dryness of mucous membranes (13.12%, xerosis with pruritus (11.15%, nose bleeding (8.31%, paronychia (5.47%, facial dermatitis (3.06%, conjunctivitis (2.84% and in addition to mucocutaneous ones, chills (2.63%, headache (2.19%, mental depression (2.19%, urinary frequency (1.53% and papilledema (0.44% were among the other observed toxicities, The relationship between mucocutaneous side effect with dosage of etretinate, sex and, age of the patients was evaluated. The association between mucoctaneous toxicities and sex was significant, sex and, age of the patients was evaluated. The association between mucocutaneous toxicities and sex was significant (P<0.05. We observed four rare side effect in the patients including hair color lightening appering as whitening or blondness, hair waving, dyspareunia and gynecomastia. In conclusion, females were more to acute mucocutaneous toxicities of etretinate.

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

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

2017-02-01

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

Acute toxicity of Psilocybe cubensis (Ear. Sing., Strophariaceae, aqueous extract in mice

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Thiago Berti Kirsten

Full Text Available Psilocybe cubensis (Ear. Sing., Strophariaceae, is a hallucinogen mushroom that has been used since the old times by humans, causing several psychotic effects. P. cubensis contains two tryptamine derivates: psilocybin and psilocin, agonists of the 5-HT2 receptor (serotonin. The main objective of this study was to investigate the acute toxicity effects of P. cubensis aqueous extract (PCAE administration in mice. Male and female adult Swiss mice received PCAE 0.1 mL/10 g i.p., and were observed individually, directly in a glass box and in an open-field. In relation to the data of the control group, PCAE-treated animals presented: an increased gnawing, appearance of wet-dog shakes and a decreased locomotion and rearing frequencies after 29-38 min. Also a clear gender difference was detected, being female mice more sensible to the PCAE than males. It was suggested that PCAE administration produced specific effects on mice behaviors, characteristic of drugs which interfere on central serotonergic and dopaminergic systems. Finally, the observational methods here employed were efficient to evaluate the toxic effects of the extract.

Efficacy of Pistacia khinjuk Fruits on Viability of Hydatid Cyst Protoscoleces and Its Acute Toxicity in Mice Model

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Hossein MAHMOUDVAND

2016-10-01

Full Text Available Background: This investigation aimed to evaluate the in vitro scolicidal effects of Pistacia khinjuk methanolic extract against protoscoleces of hydatid cysts and its acute toxicity in mice NMRI model.Methods: Protoscoleces were aseptically extracted from sheep livers having hydatid cysts. Various concentrations of the essential oil (12.5- 100 mg/mL were used for 10 to 60 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1% eosin staining. Twenty-four male NMRI mice were used to assess the acute toxicity of P. khinjuk.Results: P. khinjuk extract at the concentrations of 100 mg/mL after 10 min of exposure killed 100% of protoscoleces. Similarly, the mean of mortality rate of protoscoleces after 20 min of exposure to the concentration of 50 mg/mL was 100%. The LD50 of the intraperitoneal injection of the P. khinjuk methanolic extract was 2.8 g/kg and the maximum non-fatal dose was 1.7 g/kg.Conclusion: The findings demonstrated effective scolicidal effects of P. khinjuk extract with no considerable toxicity that might be a natural source for the producing of new scolicidal agent.

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

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Wuen Yew Teoh

2013-01-01

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

Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

International Nuclear Information System (INIS)

Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

2007-01-01

Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

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

Science.gov (United States)

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

2016-08-01

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

Acute toxic neuropathy mimicking guillain barre syndrome

Directory of Open Access Journals (Sweden)

Muhammed Jasim Abdul Jalal

2015-01-01

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

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

Science.gov (United States)

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

2010-01-01

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

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

African Journals Online (AJOL)

STORAGESEVER

2008-05-16

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

Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

International Nuclear Information System (INIS)

Gao, Yongfei; Feng, Jianfeng; Zhu, Lin

2015-01-01

Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H"+. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10"−"6 M Cd and 10"−"6 M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H"+ in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

Energy Technology Data Exchange (ETDEWEB)

Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

2015-12-15

Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

Acute toxicity of chemoradiation for rectal cancer

International Nuclear Information System (INIS)

Roedel, C.; Fietkau, R.; Keilholz, L.; Grabenbauer, G.G.; Kessler, H.; Martus, P.; Sauer, R.

1997-01-01

Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) ± 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m 2 /d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [de

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

Science.gov (United States)

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

2011-04-01

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

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

Science.gov (United States)

Tyagi, Ritu; Rana, Poonam; Khan, Ahmad Raza; Bhatnagar, Deepak; Devi, M Memita; Chaturvedi, Shubhra; Tripathi, Rajendra P; Khushu, Subash

2011-10-01

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity. Copyright © 2011 John Wiley & Sons, Ltd.

Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPARα deterioration

International Nuclear Information System (INIS)

Takahashi, Kyoko; Kamijo, Yuji; Hora, Kazuhiko; Hashimoto, Koji; Higuchi, Makoto; Nakajima, Takero; Ehara, Takashi; Shigematsu, Hidekazu; Gonzalez, Frank J.; Aoyama, Toshifumi

2011-01-01

Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPARα), suggesting the benefit of PPARα activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPARα agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPARα agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPARα deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NFκB activation. These effects are common to other fibrates and dependent on PPARα function. Interestingly, however, clofibrate pretreatment also exerted PPARα-independent tubular toxicities in PPARα-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPARα activator that has a steady serum concentration regardless of

Acute Toxicity of the Antifouling Compound Butenolide in Non-Target Organisms

KAUST Repository

Zhang, Yi-Fan

2011-08-29

Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD\\'s guideline, the predicted no effect concentration (PNEC) was 0.168 µg l^(−1), which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-06-15

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

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

African Journals Online (AJOL)

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

Acute toxicity of chemoradiation therapy (CRT) for rectal cancer: Impact of irradiated volume, type of surgery, sex and sequence of treatment modalities

International Nuclear Information System (INIS)

Fietkau, R.; Roedel, C.; Grabenbauer, G.G.; Kessler, H.; Martus, P.; Sauer, R.

1996-01-01

Purpose: In an attempt to reduce acute toxicity of CRT for rectal cancer we retrospectively evaluated potential factors that influence the severity of toxic side-effects. Materials and Methods: Between 1987 and 1995, 120 patients (pts, 73 with primary tumor, 47 with recurrent disease) received CRT for rectal cancer. RT was given by 3-4 field box technique with 6-10 MV-photons. Daily fraction size was 180 cGy, total dose 5040 cGy including 540 cGy local boost. Dose was specified to the ICRU reference point. During the first and fifth week of RT 5-FU (1000 mg/m 2 /24 h) was administered by continuous infusion for 120 hours. 56 pts received preoperative CRT, 64 pts were treated postoperatively. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 4 toxicity was limited to 3 pts (leukopenia, sepsis, arrhythmia). Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (9%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3 diarrhea (68% vs. 25%, p = 0,0003) and grade 3 leukopenia (18% vs. 8%, p = 0,03). After abdominoperineal resection less pts suffered from grade 3 diarrhea (8% vs. 47% after sphincter-preserving procedures, p = 0,0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0,02). Women had significantly more toxic side effects (grade 3 diarrhea: 39% vs. 16% in men, p = 0.04; grade 2 to 3 nausea/emesis: 21% vs. 8% in men, p = 0.018; grade 2 to 3 leukopenia: 53% vs. 31% in men, p = 0, 02). After preoperative CRT a significant reduction of grade 3 diarrhea (11% vs. 29%, p = 0.03) and grade 3 erythema (16% vs. 41%, p = 0.04) was noted. Conclusion: In order to reduce acute treatment related toxicity preoperative CRT deserves further evaluation. Careful attention should be paid to the extension of treatment volume to the paraaortic region. Individual adjustment of 5-FU dosage by monitoring its systemic

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

International Nuclear Information System (INIS)

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

2005-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

The Promise of Pharmacogenomics in Reducing Toxicity During Acute Lymphoblastic Leukemia Maintenance Treatment

Directory of Open Access Journals (Sweden)

Shoshana Rudin

2017-04-01

Full Text Available Pediatric acute lymphoblastic leukemia (ALL affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP and methotrexate (MTX, are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT, nudix hydrolase 15 (NUDT15, and potentially inosine triphosphatase (ITPA, which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1 and dihydrofolate reductase (DHFR. Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1 and thymidylate synthetase (TYMS, but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

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

Science.gov (United States)

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

2015-07-01

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

Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse.

Science.gov (United States)

Saldaña-Ruíz, Sandra; Soler-Martín, Carla; Llorens, Jordi

2012-01-25

Allylnitrile, cis-crotononitrile, and 3,3'-iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute toxicity test protocol was developed to facilitate evaluation of the vestibular toxicity by a specific behavioral test battery at doses up to sub-lethal levels while using a limited number of animals. A mean number of 8.5±0.3 animals per nitrile, strain and sex was necessary to obtain evidence of vestibular toxicity and optionally an estimation of the lethal dose. For several but not all nitriles, lethal doses significantly increased in CYP2E1-null mice. The protocol revealed the vestibular toxicity of five nitriles, including previously identified ototoxic compounds and one nitrile (trans-crotononitrile) known to have a different profile of neurotoxic effects in the rat. In all five cases, both sexes were affected and no decrease in susceptibility was apparent in CYP2E1-null mice respect to 129S1 mice. Fourteen nitriles caused no vestibular toxicity, including six nitriles tested in CYP2E1-null mice at doses significantly larger than the maximal doses that can be tested in wild type animals. We conclude that only a subset of low molecular weight nitriles is toxic to the vestibular system, that species-dependent differences exist in this vestibular toxicity, and that CYP2E1-mediated metabolism is not involved in this effect of nitriles although it has a role in the acute lethality of some of these compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-10-01

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

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

Directory of Open Access Journals (Sweden)

Ong YS

2016-11-01

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

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

Science.gov (United States)

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

2014-10-29

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

Studying the effect of CO2-induced acidification on sediment toxicity using acute amphipod toxicity test.

Science.gov (United States)

Basallote, M Dolores; De Orte, Manoela R; DelValls, T Ángel; Riba, Inmaculada

2014-01-01

Carbon capture and storage is increasingly being considered one of the most efficient approaches to mitigate the increase of CO2 in the atmosphere associated with anthropogenic emissions. However, the environmental effects of potential CO2 leaks remain largely unknown. The amphipod Ampelisca brevicornis was exposed to environmental sediments collected in different areas of the Gulf of Cádiz and subjected to several pH treatments to study the effects of CO2-induced acidification on sediment toxicity. After 10 days of exposure, the results obtained indicated that high lethal effects were associated with the lowest pH treatments, except for the Ría of Huelva sediment test. The mobility of metals from sediment to the overlying seawater was correlated to a pH decrease. The data obtained revealed that CO2-related acidification would lead to lethal effects on amphipods as well as the mobility of metals, which could increase sediment toxicity.

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

Science.gov (United States)

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

2016-09-01

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

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

Directory of Open Access Journals (Sweden)

DAYANE K.D. NASCIMENTO

2016-01-01

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

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

Science.gov (United States)

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

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

NARCIS (Netherlands)

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

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

Acute toxicity effects of perfluorooctane sulfonate on sperm vitality, kinematics and fertilization success in zebrafish

Science.gov (United States)

Xia, Jigang; Niu, Cuijuan

2017-07-01

Perfluorooctane sulfonate (PFOS) has emerged as one of the most concerning contaminants in recent years. This study aimed to investigate the acute toxicity effect of PFOS on sperm viability, kinematics and fertilization success in zebrafish ( Danio rerio). Sperm were activated in aqueous media containing a range of PFOS concentrations (0, 0.09, 0.9 and 9 mg/L). Viabilities and kinematics of the sperm exposed to different PFOS treatments were assessed via computer-assisted sperm analysis (CASA) at 20, 40, 60, and 80 s after activation. PFOS exposure decreased the percentage of motile sperm, the curvilinear velocity (VCL), and the mean angular displacement (MAD) of spermatozoa, but showed no influence on the straight-line velocity (VSL) or the angular path velocity (VAP). Furthermore, a significant decrease in fertilization success was observed in spermatozoa that were exposed to 0.9 mg/L PFOS or more. These findings indicate that PFOS pollution in natural aquatic environment may be a potential threaten to successful reproduction of fish.

ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

Science.gov (United States)

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

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

Science.gov (United States)

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

2011-11-01

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

Acute toxic effects of endosulfan sulfate on three life stages of grass shrimp, Palaemonetes pugio.

Science.gov (United States)

Key, Peter B; Chung, Katy W; Venturella, John J; Shaddrick, Brian; Fulton, Michael H

2010-01-01

In this study, the toxicity of endosulfan sulfate, the primary degradation product of the insecticide endosulfan, was determined in three life stages of the grass shrimp (Palaemonetes pugio). After 96 h exposure to endosulfan sulfate, the grass shrimp adult LC50 was 0.86 microg/L (95% CI 0.56-1.31), the grass shrimp larvae LC50 was 1.64 microg/L (95% CI 1.09-2.47) and the grass shrimp embryo LC50 was 45.85 microg/L (95% CI 23.72-88.61 microg/L). This was compared to the previously published grass shrimp 96-h LC50s for endosulfan. The toxicity of the two compounds was similar for the grass shrimp life stages with adults more sensitive than larvae and embryos. The presence of sediment in 24h endosulfan sulfate-exposures raised LC50s for both adult and larval grass shrimp but not significantly. The USEPA expected environmental concentrations (EEC) for total endosulfan and endosulfan sulfate and the calculations of risk quotients (RQ) based on the more sensitive adult grass shrimp 96-h LC50 clearly show that environmental concentrations equal to acute EECs would prove detrimental to grass shrimp or other similarly sensitive aquatic organisms. These results indicate that given the persistence and toxicity of endosulfan sulfate, future risk assessments should consider the toxicity potential of the parent compound as well as this degradation product.

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

Science.gov (United States)

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

2016-01-01

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

Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

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Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

2007-09-25

Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

Acute and additive toxicity of ten photosystem-II herbicides to seagrass.

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Wilkinson, Adam D; Collier, Catherine J; Flores, Florita; Negri, Andrew P

2015-11-30

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.

Acute and additive toxicity of ten photosystem-II herbicides to seagrass

Science.gov (United States)

Wilkinson, Adam D.; Collier, Catherine J.; Flores, Florita; Negri, Andrew P.

2015-11-01

Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/Fm‧) by 50% at concentrations ranging from 3.5 μg l-1 (ametryn) to 132 μg l-1 (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/Fm‧.

A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients

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Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.

2013-01-01

Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306

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

Science.gov (United States)

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

2018-01-01

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

Acute toxicity of ammonia to blue tilapia, Oreochromis aureus in ...

African Journals Online (AJOL)

The acute toxicity of blue tilapia, Oreochromis aureus (3.28 ± 0.36 g in body weight, 61.84 ± 2.08 mm in body length) exposed to environmental un-ionized ammonia at different salinities (1, 8, 12, 16 and 20 ppt) was assessed via a series of static exposure trials. Median lethal concentrations of 24 h of exposure were ...

Acute Toxicity of Delsate® Herbicide (Glyphosate) On Albumin and ...

African Journals Online (AJOL)

Some biochemical metabolism [albumin and blood urea nitrogen (BUN)] were monitored in the serum of fresh water adult African Catfish, Clarias gariepinus exposed to acute concentrations of Delsate herbicide for 96 hours. The concentrations of the toxicant tested were 0.5 mgL-1, 1.0 mgL-1, 1.5 mgL-1, 2.0 mgL-1 and 2.5 ...

Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

Energy Technology Data Exchange (ETDEWEB)

Vukov, Oliver, E-mail: vuko3930@mylaurier.ca [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); Smith, D. Scott [Chemistry Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); McGeer, James C. [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada)

2016-01-15

The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO{sub 3} mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy{sup 3+} toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific

Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

International Nuclear Information System (INIS)

Vukov, Oliver; Smith, D. Scott; McGeer, James C.

2016-01-01

The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO 3 mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy 3+ toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific water quality

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

Science.gov (United States)

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

2017-07-01

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

Anti-diabetic effects of Inonotus obliquus polysaccharides-chromium (III) complex in type 2 diabetic mice and its sub-acute toxicity evaluation in normal mice.

Science.gov (United States)

Wang, Cong; Chen, Zhongqin; Pan, Yuxiang; Gao, Xudong; Chen, Haixia

2017-10-01

Polysaccharides are important bioactive ingredients from Inonotus obliquus. This study aimed to synthesize and characterize a novel I. obliquus polysaccharides-chromium (III) complex (UIOPC) and investigate the anti-diabetic effects in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) mice and sub-acute toxicity in normal mice. The molecular weight of UIOPC was about 11.5 × 10 4  Da with the chromium content was 13.01% and the chromium was linked with polysaccharides through coordination bond. After treatment of UIOPC for four weeks, the body weight, fasting blood glucose (FBG) levels, plasma insulin levels of the diabetic mice were significantly reduced when compared with those of the diabetic mice (p < 0.05). The results on serum profiles and antioxidant enzymes activities revealed that UIOPC had a positive effect on hypoglycemic and antioxidant ability. Histopathology results showed that UIOPC could effectively alleviate the STZ-lesioned tissues in diabetic mice. Furthermore, high dose administration of UIOPC had no obviously influence on serum profiles levels and antioxidant ability of the normal mice and the organ tissues maintained organized and integrity in the sub-acute toxicity study. These results suggested that UIOPC might be a good candidate for the functional food or pharmaceuticals in the treatment of T2DM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models--a systematic review and meta-analysis.

Science.gov (United States)

Heard, Kennon; Cleveland, Nathan R; Krier, Shay

2011-11-01

There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%-38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%-60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models.

Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum oxide nanoparticle toxicity in fresh water environment.

Directory of Open Access Journals (Sweden)

Sunandan Pakrashi

Full Text Available Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h in conjunction with the effects from the nano-sized particles in the initial phases (24 h puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake as substantiated through the transmission electron microscopy (TEM and inductively coupled plasma optical emission spectral (ICP-OES analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system.

Acute Oncology Care: A narrative review of the acute management of neutropenic sepsis and immune-related toxicities of checkpoint inhibitors.

Science.gov (United States)

Knight, Thomas; Ahn, Shin; Rice, Terry W; Cooksley, Tim

2017-11-01

Cancer care has become increasingly specialized and advances in therapy have resulted in a larger number of patients receiving care. There has been a significant increase in the number of patients presenting with cancer related emergencies including treatment toxicities and those directly related to the malignancy. Suspected neutropenic sepsis is an acute medical emergency and empirical antibiotic therapy should be administered immediately. The goal of empirical therapy is to cover the most likely pathogens that will cause life-threatening infections in neutropenic patients. Patients with febrile neutropenia are a heterogeneous group with only a minority of treated patients developing significant medical complications. Outpatient management of low risk febrile neutropenia patients identified by the MASCC score is a safe and effective strategy. Immunotherapy with "checkpoint inhibitors" has significantly improved outcomes for patients with metastatic melanoma and evidence of benefit in a wide range of malignancies is developing. Despite these clinical benefits a number of immune related adverse events have been recognised which can affect virtually all organ systems and are potentially fatal. The timing of the onset of the adverse events is dependent on the organ system affected and unlike anti-neoplastic therapy can be delayed significantly after initiation or completion of therapy. The field of Acute Oncology is changing rapidly. Alongside, the traditional challenge of neutropenic sepsis there are many emerging toxicities. Further research into the optimal management, strategies and pathways of acutely unwell patients with cancer is required. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Functional nature of the spasmolytic effect, phytochemical composition and acute toxicity studies on Sauromatum guttatum

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Nabi Shah

2014-06-01

Full Text Available The aim of the present work was to study the functional nature of the potential spasmolytic effect of the crude extract of Sauromatum guttaum. It was found positive for the presence of alkaloid and tannins. In isolated rabbit jejunum preparation, S. guttaum caused inhibition of spontaneous and high K+ (80 mM-induced contractions, with respective EC50 values (95% confidence intervals of 1.50 mg/mL (0.69-3.02 and 1.17 mg/mL (0.81-1.61, similar to verapamil. Inhibition of high K+ -induced contractions suggests Ca++ antagonistic effect. The Ca++channel blocker activity of S. guttaum was confirmed when pre-treatment of the tissues with extract (0.3-3 mg/mL caused a rightward displacement in the Ca++ concentration-response curves. Moreover, in the acute toxicity test, S. guttaum was found safe up to the dose of 3 g/kg. The findings of the current study suggest that the S. guttaum exhibited spasmolytic activity, possibly mediated through inhibitory effect on Ca++ entry and was found safe and this current study provides first evidence to the potential use of this plant as antispasmodic and can play a possible role as antidiarrheal.

In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae).

Science.gov (United States)

Assam, Assam J P; Dzoyem, J P; Pieme, C A; Penlap, V B

2010-07-27

Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of Sida rhombifolia Linn (Malvaceae) against seven pathogenic bacteria involved in diarrhoea. Acute toxicity of the most active extract was determined and major bioactive components were screened. The agar disc diffusion and the agar dilution method were used for the determination of inhibition diameters and the Minimum Inhibitory Concentration (MICs) respectively. The acute toxicity study was performed according WHO protocol. The aqueous-methanol extract (1v:4v) was the most active with diameters of inhibition zones ranging from 8.7 - 23.6 mm, however at 200 microg/dic this activity was relatively weak compared to gentamycin. The MICs of the aqueous-methanol extract (1v:4v) varied from 49.40 to 78.30 microg/ml. Salmonella dysenteriae was the most sensitive (49.40 microg/ml). For the acute toxicity study, no deaths of rats were recorded. However, significant increase of some biochemical parameters such as aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine (CRT) were found. The phytochemical analysis of the aqueous methanol extract indicated the presence of tannins, polyphenols, alkaloids, glycosides, flavonoids and saponins The results showed that the aqueous-methanol extract of S. rhombifolia exhibited moderate antibacterial activity. Some toxic effects were found when rats received more than 8 g/kg bw of extract.

Small Microbial Three-Electrode Cell Based Biosensor for Online Detection of Acute Water Toxicity.

Science.gov (United States)

Yu, Dengbin; Zhai, Junfeng; Liu, Changyu; Zhang, Xueping; Bai, Lu; Wang, Yizhe; Dong, Shaojun

2017-11-22

The monitoring of toxicity of water is very important to estimate the safety of drinking water and the level of water pollution. Herein, a small microbial three-electrode cell (M3C) biosensor filled with polystyrene particles was proposed for online monitoring of the acute water toxicity. The peak current of the biosensor related with the performance of the bioanode was regarded as the toxicity indicator, and thus the acute water toxicity could be determined in terms of inhibition ratio by comparing the peak current obtained with water sample to that obtained with nontoxic standard water. The incorporation of polystyrene particles in the electrochemical cell not only reduced the volume of the samples used, but also improved the sensitivity of the biosensor. Experimental conditions including washing time with PBS and the concentration of sodium acetate solution were optimized. The stability of the M3C biosensor under optimal conditions was also investigated. The M3C biosensor was further examined by formaldehyde at the concentration of 0.01%, 0.03%, and 0.05% (v/v), and the corresponding inhibition ratios were 14.6%, 21.6%, and 36.4%, respectively. This work provides a new insight into the development of an online toxicity detector based on M3C biosensor.

Acute Toxicity of Castor Oil Bean Extract and Tolerance Level of ...

African Journals Online (AJOL)

The experiment was carried out to determine the acute toxicity of raw castor oil bean (Ricinus communis) extract and the tolerance level of raw castor oil bean by broilers. The seeds were ground, defatted with petroleum ether and the residue was subjected to extraction with phosphate-buffered saline. The extract volume ...

Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity

Energy Technology Data Exchange (ETDEWEB)

Gamelli, R.L.; Foster, R.S. Jr.

1983-10-01

Mice were used to study the effects of protein-calorie malnutrition and its reversal on granulocyte-macrophage production and fluorouracil's toxic effect on bone marrow. An in vitro quantitative clonal culture technique for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used. Animals on a protein-free but otherwise complete diet for ten days had a significant contraction in total marrow cellularity and GM-CFC numbers paralleling the animal's weight loss. The acute toxic effect of fluorouracil on bone marrow was not increased in protein-deprived animals. On refeeding, there was a biphasic response in the degree of toxic effect on marrow. Animals refed for one day had significantly increased fluorouracil-related marrow abnormalities. However, animals refed for four days, when marrows were repleted, were partially protected from the drug's cytotoxic effects. The increased sensitivity in mice refed for one day was related to more GM-CFC in active DNA synthesis.

Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

International Nuclear Information System (INIS)

Rebagay, T.V.; Dodd, D.A.; Lockrem, L.L.; Voogd, J.A.

1993-01-01

Liquid wastes containing radioactive, hazardous, and regulated chemicals have been generated throughout the 50 years operation of the Hanford Site of the US Department of Energy near Richland, Washington. The current strategy for the disposal of the low-level radioactive portion of these wastes involves immobilization of the waste in the form of grout. Because the potential risk of animal and plant exposure to grouts is unknown, acute toxicity screening of grouts is needed. Grouts were prepared by mixing a surrogate nonradioactive liquid waste with a blend consisting of cement, fly ash, and clay. Aqueous extracts of the grout were then screened for acute toxicity using aquatic invertebrates as test organisms and a fluorogenic substrate as the toxic stress indicator. After a 1-hour exposure of juvenile daphnids (D, magna, D. pulex, and C. dubia) to the grout extracts followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The EC50 values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The slight difference in the responses may be attributed to the subjective pass-fail scoring of the fluorescence criterion. The results indicated that the grout studied is nonhazardous and nondangerous

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

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

2006-10-01

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

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

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

2013-01-01

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

Acute toxicity of dichloroacetonitrile (DCAN), a typical nitrogenous disinfection by-product (N-DBP), on zebrafish (Danio rerio).

Science.gov (United States)

Lin, Tao; Zhou, Dongju; Dong, Jian; Jiang, Fuchun; Chen, Wei

2016-11-01

Dichloroacetonitrile (DCAN) is a typical nitrogenous disinfection by-product (N-DBP) and its toxicity on aquatic animals is investigated for the first time. The present study was designed to investigate the potential adverse effects of DCAN on zebrafish. DCAN could induce developmental toxicity to zebrafish embryos. A significant decrease in hatchability and an increase in malformation and mortality occurred when DCAN concentration was above 100µg/L. Heart function alteration and neuronal function disturbance occurred at concentration higher than 500 and 100µg/L, respectively. Further, DCAN was easily accumulated in adult zebrafish. The rank order of declining bioconcentration factor (BCF) was liver (1240-1670)> gill (1210-1430)> muscle (644-877). DCAN caused acute metabolism damage to adult zebrafish especially at 8 days exposure, at which time the "Integrated Biomarker Response" (IBR) index value reached 798 at 1mg/L DCAN dose. Acute DNA damage was induced to adult zebrafish by DCAN even at 10µg/L dose. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Toxicity of Justicia gendarussa Burm. Leaves

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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.

Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients

International Nuclear Information System (INIS)

Tanimoto, Ryuta; Bekku, Kensuke; Katayama, Norihisa

2013-01-01

The objectives of this study were to describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On multivariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100. (author)

Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

Energy Technology Data Exchange (ETDEWEB)

1986-09-01

Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity

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Beltrán César

2011-08-01

Full Text Available Abstract Background Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. Methods In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. Results The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%, abdomen (17% and thorax (6%. The most prevalent histological types were: medulloblastoma (16 patients, neuroblastoma (9 patients and rhabdomyosarcoma (7 patients. A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72% were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy. In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6% of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6% had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases were significantly associated with severe toxicity (grade 3 or more, whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. Conclusion HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of

Helical tomotherapy in the treatment of pediatric malignancies: a preliminary report of feasibility and acute toxicity

International Nuclear Information System (INIS)

Mesbah, Latifa; Marsiglia, Hugo; Matute, Raúl; Usychkin, Sergey; Marrone, Immacolata; Puebla, Fernando; Mínguez, Cristina; García, Rafael; García, Graciela; Beltrán, César

2011-01-01

Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly

Investigation of a Brazilian tannery effluent by means of zebra fish (Danio rerio) embryo acute toxicity (FET) test.

Science.gov (United States)

Rocha, Otávio Pelegrino; De Oliveira, Danielle Palma

2017-01-01

Tannery effluents consist of a complex chemical composition not only limited to primary pollutants, which also require biological detection as these compounds may produce adverse effects. The fish embryo toxicity (FET) test with Danio rerio is an alternative method in hazard and risk assessment for determination of chemical-mediated effects. The aim of this investigation was to use the FET test to detect compounds and consequent effects in Brazilian tannery effluents. Samples were collected from the inlet and outlet of the effluent treatment plant at a tannery located in Restinga, São Paulo, Brazil. The toxicological effects were assessed using FET assay for a period of 144 hr using indices such as (1) coagulation of fertilized eggs, (2) lack of detachment of tail-bud from yolk sac, (3) absence of spontaneous movement, (4) yolk sack edema, (5) malformation of the tail, (6) scoliosis, and (7) deformation of swim bladder in the embryos. Data showed that effluent treatment plant exposure produced acute toxicity in D. rerio embryos as evidenced by coagulation of fertilized eggs in up to 5% of all diluted samples 24 hr post fertilization for inlet effluent samples compared to 100% coagulation for outlet samples. Results demonstrated that these effects may not be attributed to metals, but to other non-detected components, such as dyes, pigments, biocides, carriers, surfactants, or other organic compounds that might be present in these complex mixtures. The use of D. rerio embryos was found to be useful as an additional tool for ecotoxicity testing to assess the potential environmental acute toxicity influence of tannery effluents.

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

Science.gov (United States)

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

1990-02-01

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

Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

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George Yang

2015-06-01

Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

Energy Technology Data Exchange (ETDEWEB)

Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

2015-05-15

Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

Guidance on health effects of toxic chemicals. Safety Analysis Report Update Program

Energy Technology Data Exchange (ETDEWEB)

Foust, C.B.; Griffin, G.D.; Munro, N.B.; Socolof, M.L.

1994-02-01

Martin Marietta Energy Systems, Inc. (MMES), and Martin Marietta Utility Services, Inc. (MMUS), are engaged in phased programs to update the safety documentation for the existing US Department of Energy (DOE)-owned facilities. The safety analysis of potential toxic hazards requires a methodology for evaluating human health effects of predicted toxic exposures. This report provides a consistent set of health effects and documents toxicity estimates corresponding to these health effects for some of the more important chemicals found within MMES and MMUS. The estimates are based on published toxicity information and apply to acute exposures for an ``average`` individual. The health effects (toxicological endpoints) used in this report are (1) the detection threshold; (2) the no-observed adverse effect level; (3) the onset of irritation/reversible effects; (4) the onset of irreversible effects; and (5) a lethal exposure, defined to be the 50% lethal level. An irreversible effect is defined as a significant effect on a person`s quality of life, e.g., serious injury. Predicted consequences are evaluated on the basis of concentration and exposure time.

Acute and chronic toxicity of copper to the euryhaline rotifer, Brachionus plicatilis ("L" strain).

Science.gov (United States)

Arnold, W R; Diamond, R L; Smith, D S

2011-02-01

This article presents data from original research, intended for the use in the development of copper (Cu) criteria for the protection of estuarine and marine organisms and their uses in the United States. Two 48-h static-acute toxicity tests-one with and one without added food-and a 96-h static multigeneration life-cycle test (P1-F2 generations) were performed concurrently using the euryhaline rotifer Brachionus plicatilis ("L" strain) to develop a Cu acute-to-chronic ratio (ACR) for this species. Tests were performed at 15 g/L salinity, at 25°C, and the exposure concentrations of dissolved Cu were verified. Supplemental chemical analyses were performed and reported for the development of a Cu-saltwater biotic ligand model (BLM). Supplemental analyses included alkalinity, calcium, chloride, dissolved organic carbon (DOC), hardness, magnesium, potassium, sodium, and temperature. The acute toxicity test measurement end points were the dissolved Cu median lethal concentration (LC₅₀) values based on rotifer survival. The chronic measurement end points were the dissolved Cu no-observed-effect concentration (NOEC), lowest-observed-effect concentration (LOEC), EC₂₅, EC₂₀, and EC₁₀ based on the intrinsic rate of rotifer population increase (r). The 48-h LC₅₀(Fed), 48-h LC₅₀(Unfed), 96-h NOEC, 96-h LOEC, EC₂₅, EC₂₀, and EC₁₀ were 20.8, 13.4, 6.1, 10.3, 11.7, 10.9, and 8.8 μg Cu/L, respectively. The ACRs were calculated as ratios of each 48-h LC₅₀ value [fed and unfed) and each of the 96-h chronic values (ChV; geometric mean of NOEC and LOEC)], EC₁₀, EC₂₀, and EC₂₅. The ACRs ranged from 1.15 to 2.63.

Acute and subacute toxicity of {sup 18}F-FDG; Toxicidade aguda e subaguda do radiofarmaco {sup 18}F-FDG

Energy Technology Data Exchange (ETDEWEB)

Dantas, Danielle Maia

2013-07-01

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

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

Directory of Open Access Journals (Sweden)

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.

A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma. A report on acute toxicity

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Norkus, Darius; Miller, Albert; Kurtinaitis, Juozas; Valuckas, Konstantinas Povilas [Dept. of Radiotherapy, Inst. of Oncology, Vilnius Univ. (Lithuania); Haverkamp, Uwe [Dept. of Radiology, Clemenshospital, Muenster (Germany); Popov, Sergey [Dept. of Radiotherapy, Riga Eastern Hospital, Latvian Oncology Center, Riga (Latvia); Prott, Franz-Josef [Inst. of Radiology and Radiotherapy (RNS), St. Josefs Hospital, Wiesbaden (Germany)

2009-11-15

Purpose: to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). Patients and methods: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8-10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. Results: no acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% ({chi}{sup 2}-test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). Conclusion: in this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule's safety in the long term. (orig.)

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

International Nuclear Information System (INIS)

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio; Fellin, Gianni; Magli, Alessandro; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Greco, Carlo; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Vavassori, Vittorio

2008-01-01

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

Directory of Open Access Journals (Sweden)

Williams Scott

2011-10-01

Full Text Available Abstract Background Image-guided radiotherapy (IGRT increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically. Methods Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment. Results In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188. Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174. Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271. The median number of days with a toxicity was higher for ≥G2 (p = 0.0179 and ≥G3 frequency (p = 0.0027, ≥G2 diarrhoea (p = 0.0033 and ≥G2 fatigue (p = 0.0088 in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference. Conclusions In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

International Nuclear Information System (INIS)

Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

2011-01-01

Highlights: → Toxicological implications associated with the use of NaNO 2 therapy to treat systemic cell-free Hb exposure are not well-defined. → Systemic Hb exposure followed by NaNO 2 infusion induces acute CNS toxicities in guinea pigs. → These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO 2 alone. → NaNO 2 -mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO 2 ) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO 2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO 2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO 2 , at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO 2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Acute Toxicity of Opuntia Ficus Indica and Pistacia Lentiscus Seed Oils in Mice

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

2012-01-01

Opuntia ficus indica and Pistacia lentiscus L. seeds are used in traditional medicine. The objective of this study was to investigate the toxicity of the fixed oil of Opuntia ficus indica and Pistacia lentiscus L. seeds in mice through determination of LD50 values, and also the physicochemical characteristics of the fixed oil of these oils. The acute toxicity of their fixed oil were also investigated in mice using the method of Kabba and Berhens. The fixed oil of Pistacia lentiscus and Opunti...

Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

International Nuclear Information System (INIS)

Romanelli, Maria Fernanda

2004-01-01

Surfactants are synthetic organic compounds widely used in cosmetic, food, textile, dyers and paper production industries and in particular detergents and others cleaning products industries. The world consumption is nearly 8 million tons per year. One of the main environmental issues coming from the use of these compounds is their toxicity that compromises the biological treatment of effluents and the quality of receiving waters. The objective of this work was the application of ionizing radiation by electron beam in the degradation and reduction of acute and chronic toxicities of surfactants sodium dodecylsulfate (SDS), dodecyl p-benzenesulfonate acid (LAS) and sodium dodecyl p-benzenesulfonate (LAS). This treatment technology has been studied as a pre-treatment for effluents containing toxic and non-biodegradable compounds, before the biological treatment. Two acute toxicity assays were employed, one with the micro-crustacean Daphnia similis and the other with the luminescent bacterium Vibrio fischeri along with a chronic toxicity assay with the micro-crustacean Ceriodaphnia dubia (just for SDS and acid LAS) for the non-irradiated and irradiated samples and radiation doses 3.0 kGy, 6.0 kGy, 9.0 kGy and 12.0 kGy. Physical-chemical parameters were evaluated for the following up the degradation of the surfactant molecules. The reductions of acute toxicity varied between 72.49% and 90.98% for SDS, 18.22% and 78.98% for acid LAS and 82.66% and 94.26% for sodium LAS. For the chronic toxicity, the reduction percentages varied between 64.03% and 83.01% for SDS and 47.48% and 64.91% for acid LAS. When one considers the application of the electron beam as a pre-treatment of effluents containing high concentrations of surfactants, the toxicity is an essential parameter allowing the further biological treatment of these effluents. (author)

Acute toxicity assessment of perfluorinated carboxylic acids towards the Baltic microalgae.

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Latała, Adam; Nędzi, Marcin; Stepnowski, Piotr

2009-09-01

The presence of high-energy carbon-fluorine bonds in perfluoro compounds lends them great stability and causes them to be environmentally persistent. Relatively little is known about the acute toxicity of perfluorinated carboxylic acids (PFCAs) to ecotoxicological markers such as aquatic plants and animals. This study tested the toxicity of these compounds to the green alga Chlorella vulgaris, the diatom Skeletonema marinoi and the blue-green alga Geitlerinema amphibium, which are species representative of the algal flora of the Baltic Sea. The EC(50) values obtained range from 0.28 mM to 12.84 mM. A distinct relationship between hydrophobicity and toxicity is demonstrated. For every extra perfluoromethylene group in the alkyl chain, the toxicity increases twofold. LogEC(50) values are very well correlated linearly with both the number of carbon atoms in the perfluoroalkyl chain and the partition coefficients. The results also indicate that there are clear differences between the responses of particular taxonomic groups of algae: blue-green algae and diatoms are far more sensitive to PFCAs than green algae, probably because of differences in cell wall structure.

Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: Topical intrarectal versus subcutaneous application

International Nuclear Information System (INIS)

Kouloulias, Vassilis E.; Kouvaris, John R.; Pissakas, George; Mallas, Elias; Antypas, Christos; Kokakis, John D.; Matsopoulos, George; Michopoulos, Spyros; Mystakidou, Kyriaki; Vlahos, Lambros J.

2005-01-01

Purpose: To investigate the cytoprotective effect of subcutaneous vs. intrarectal administration of amifostine against acute radiation toxicity. Methods and materials: Patients were randomized to receive amifostine either intrarectally (Group A, n = 27) or a 500-mg flat dose subcutaneously (Group B, n = 26) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In Group A, 1,500 mg of amifostine was administered intrarectally as an aqueous solution in 40 mL of enema. Two different toxicity scales were used: the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (RTOG) rectal and urologic toxicity criteria and the Subjective-RectoSigmoid scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after radiotherapy completion. The area under the curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index. Results: Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, Group A had superior results with a significantly lower incidence of Grades I-II rectal radiation morbidity (11% vs. 42%, p 0.04) but inferior results concerning urinary toxicity (48% vs. 15%, p 0.03). The mean rectal mucositis index and Subjective-RectoSigmoid score were significantly lower in Group A (0.44 vs. 2.45 [p = 0.015] and 3.9 vs. 6.0 [p = 0.01], respectively), and the mean urinary mucositis index was lower in Group B (2.39 vs. 0.34, p < 0.028). Conclusions: Intrarectal administration of amifostine (1,500 mg) seemed to have a cytoprotective efficacy in acute radiation rectal mucositis but was inferior to subcutaneous administration in terms of urinary toxicity. Additional randomized studies are needed for definitive decisions concerning the

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

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

2018-01-02

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

Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

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Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

2010-01-01

Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 ± 3mm (mean ± SD) and 10 ± 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 ± 13cGy with Hylaform vs. 106 ± 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

Ecotoxicological evaluation of leachate from the Limeira sanitary landfill with a view to identifying acute toxicity

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José Euclides Stipp Paterniani; Ronaldo Teixeira Pelegrini; Núbia Natália de Brito Pelegrini

2007-01-01

Final disposal of solid waste is still a cause for serious impacts on the environment. In sanitary landfills, waste undergoes physical, chemical, and biological decomposition, generating biogas and leachate. Leachate is a highly toxic liquid with a very high pollution potential. The purpose of this work is to evaluate toxicity of in natura leachate samples collected from Limeira Sanitary Landfill, in Limeira, SP. The ecotoxicological evaluation comprised acute toxicity assays using as test or...

High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

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Wolff, Hendrik Andreas; Bosch, Jan; Hennies, Steffen; Hess, Clemens F.; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Overbeck, Tobias [Dept. of Haematology and Oncology, Univ. Medicine Goettingen (Germany); Matthias, Christoph; Roedel, Ralph M. [Dept. of Otorhinolaryngology, Univ. Medicine Goettingen (Germany)

2010-05-15

Purpose: to test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and methods: from 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC {>=} 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis. Results: a statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC {>=} 3 acute organ toxicity had a 5-year overall survival rate of 4% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure. Conclusion: these data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials. (orig.)

The toxic effects of chlorophenols and associated mechanisms in fish

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Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun

2017-01-01

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

The toxic effects of chlorophenols and associated mechanisms in fish

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Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun, E-mail: huangdj@lzu.edu.cn

2017-03-15

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

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Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Acute Lidocaine Toxicity: a Case Series

Directory of Open Access Journals (Sweden)

Mitra Rahimi

2018-06-01

Full Text Available Introduction: Parenteral form of lidocaine is the best-known source of lidocaine poisoning. This study aimed to evaluate the characteristics of acute lidocaine toxicity.Methods: In this retrospective cross-sectional study, demographics, clinical presentation, laboratory findings, and outcome of patients intoxicated with lidocaine (based on  ICD10 codes admitted to Loghman Hakim Hospital, during April 2007 to March 2014 were analyzed.Results: 30 cases with the mean age of 21.83 ± 6.57 year were studied (60% male. All subjects had used either 6.5% lidocaine spray or 2% topical formulations of lidocaine. The mean consumed dose of lidocaine was 465 ± 318.17 milligrams. The most frequent clinical presentations were nausea and vomiting (50%, seizure (33.3%, and loss of consciousness (16.7%. 22 (73.3% cases had normal sinus rhythm, 4 (13.3% bradycardia, 2 (6.7% ventricular tachycardia, and 2 (6.7% had left axis deviation. 11 (36.6% cases were intubated and admitted to intensive care unit (ICU for 6.91 ± 7.16 days. Three patients experienced status epilepticus that led to cardiac arrest, and death (all cases with suicidal intention.Conclusion: Based on the results of this study, most cases of topical lidocaine toxicity were among < 40-year-old patients with a male to female ratio of 1.2, with suicidal attempt in 90%, need for intensive care in 36.6%, and  mortality rate of 10%.

Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

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Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

2014-07-01

Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy

International Nuclear Information System (INIS)

Ragab, Omar; Park, Sang-June; Zhang, Mingle; Wang, Jason; Velez, Maria; Demanes, David J.; Banerjee, Robyn; Patel, Shyamal; Kamrave, Mitchell

2018-01-01

To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

Acute skin toxicity-related, out-of-pocket expenses in patients with breast cancer treated with external beam radiotherapy: a descriptive, exploratory study.

Science.gov (United States)

Schnur, Julie B; Graff Zivin, Joshua; Mattson, David M K; Green, Sheryl; Jandorf, Lina H; Wernicke, A Gabriella; Montgomery, Guy H

2012-12-01

Acute skin toxicity is one of the most common side effects of breast cancer radiotherapy. To date, no one has estimated the nonmedical out-of-pocket expenses associated with this side effect. The primary aim of the present descriptive, exploratory study was to assess the feasibility of a newly developed skin toxicity costs questionnaire. The secondary aims were to: (1) estimate nonmedical out-of-pocket costs, (2) examine the nature of the costs, (3) explore potential background predictors of costs, and (4) explore the relationship between patient-reported dermatologic quality of life and expenditures. A total of 50 patients (mean age = 54.88, Stage 0-III) undergoing external beam radiotherapy completed a demographics/medical history questionnaire as well as a seven-item Skin Toxicity Costs (STC) questionnaire and the Skindex-16 in week 5 of treatment. Mean skin toxicity costs were $131.64 (standard error [SE] = $23.68). Most frequently incurred expenditures were new undergarments and products to manage toxicity. Education was a significant unique predictor of spending, with more educated women spending more money. Greater functioning impairment was associated with greater costs. The STC proved to be a practical, brief measure which successfully indicated specific areas of patient expenditures and need. Results reveal the nonmedical, out-of-pocket costs associated with acute skin toxicity in the context of breast cancer radiotherapy. To our knowledge, this study is the first to quantify individual costs associated with this treatment side effect, as well as the first to present a scale specifically designed to assess such costs. In future research, the STC could be used as an outcome variable in skin toxicity prevention and control research, as a behavioral indicator of symptom burden, or as part of a needs assessment.

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

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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.

ACUTE TOXICITY OF FIVE SEDIMENT-ASSOCIATED METALS, INDIVIDUALLY AND IN A MIXTURE, TO THE ESTUARINE MEIOBENTHIC HARPACTICOID COPEPOD AMPHIASCUS TENUIREMIS. (R825279)

Science.gov (United States)

AbstractThe acute effects of many individual, seawater-solubilized metals on meiobenthic copepods and nematodes are well known. In sediments, however, metals most often occur as mixtures, and it is not known whether such mixtures exhibit simple additive toxicity to me...

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

International Nuclear Information System (INIS)

Lips, Irene M; Dehnad, Homan; Gils, Carla H van; Boeken Kruger, Arto E; Heide, Uulke A van der; Vulpen, Marco van

2008-01-01

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

Directory of Open Access Journals (Sweden)

Boeken Kruger Arto E

2008-05-01

Full Text Available Abstract We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment and weekly during treatment (acute toxicity were scored using the Common Toxicity Criteria (CTC. The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU complaints and 2% experienced grade 2 gastrointestinal (GI complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4. In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

International Nuclear Information System (INIS)

Haj Mohammad, Nadia; Hulshof, Maarten CCM; Bergman, Jacques JGHM; Geijsen, Debby; Wilmink, Johanna W; Berge Henegouwen, Mark I van; Laarhoven, Hanneke WM van

2014-01-01

Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Haj Mohammad, Nadia [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hulshof, Maarten CCM [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Bergman, Jacques JGHM [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Geijsen, Debby [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Wilmink, Johanna W [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Berge Henegouwen, Mark I van [Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Laarhoven, Hanneke WM van [Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2014-01-31

Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy/1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

Acute silver toxicity in aquatic animals is a function of sodium uptake rate

DEFF Research Database (Denmark)

Bianchini, A.; Grosell, Martin Hautopp; Gregory, S.

2002-01-01

-specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from...... toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarus diogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above...... hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity...

Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial

International Nuclear Information System (INIS)

Pollack, Alan; Hanlon, Alexandra L.; Horwitz, Eric M.; Feigenberg, Steven J.; Konski, Andre A.; Movsas, Benjamin; Greenberg, Richard E.; Uzzo, Robert G.; Ma, C.-M. Charlie; McNeeley, Shawn W.; Buyyounouski, Mark K.; Price, Robert A.

2006-01-01

Purpose: The α/β ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. Patients and Methods: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. Results: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. Conclusion: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described

Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

Energy Technology Data Exchange (ETDEWEB)

Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Paumen, M.L.; Dmytrasz, B.

2011-12-15

This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

Acute aquatic toxicity of heavy fuel oils. Summary of relevant test data

International Nuclear Information System (INIS)

Comber, M.I.H.; Den Haan, K.; Djemel, N.; Eadsforth, C.V.; King, D.; Parkerton, T.; Paumen, M.L.; Dmytrasz, B.

2011-12-01

This report describes the experimental procedures and results obtained in acute ecotoxicity tests on several heavy fuel oil (HFO) samples. Water accommodated fractions (WAFs) of these samples were tested for toxicity to the rainbow trout (Oncorhynchus mykiss), the crustacean zooplankter (Daphnia magna) and green algae (Selenastrum capricornutum). These results assist in determining the environmental hazard from heavy fuel oil.

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

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Mildred García-González

2006-12-01

Full Text Available We tested the effects of the aqueous extract of Petiveria alliacea leaves on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice of 20 to 25 g mean weight. Treatments were in all cases doses of 1 000 and 2 000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week. Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1 000 mg/kg dose but not for the higher 2 000 mg/kg dose. After administering the doses once after a starving period of six hours, no significant differences in intestinal motility could be found. Rev. Biol. Trop. 54 (4: 1323-1326. Epub 2006 Dec. 15Se evaluaron los efectos del estracto acuoso de las hojas de Petiveria alliacea, en la toxicidad aguda y toxicidad subcrónica, hematocritos, niveles de glucosa en la sangre y motilidad intestinal del ratón macho albino NGP, con un peso promedio de 20 a 25g. En todos los casos los tratamientos fueron dosis de 1 000 y 2 000 mg/kg de peso del animal y un tratamiento control con 0.5 ml de agua destilada, usando 10 animales por tratamiento y administrado oralmente cinco días por semana. Los períodos experimentales fueron de 18 y 70 días para toxicidad aguda y toxicidad subcrónica, respectivamente. No se observaron signos de mortalidad ni de toxidad en ambas pruebas. Con la dosis de 1 000 mg/kg hubo un leve pero significativo incremento en los niveles de glucosa durante las primeras tres semanas, pero no con la dosis más alta de 2 000 mg/kg. Después de administrar las dosis luego de un período de hambre de seis horas, no se encontraron diferencias significativas en la motilidad intestinal

Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model

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Charles A. Easley, IV

2015-05-01

Full Text Available Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP and 1,2,dibromo-3-chloropropane (DBCP on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.

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

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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.

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

Science.gov (United States)

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

2015-05-01

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

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

2011-06-10

Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

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

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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.

Comprehensive characterization of the acute and chronic toxicity of the neonicotinoid insecticide thiamethoxam to a suite of aquatic primary producers, invertebrates, and fish.

Science.gov (United States)

Finnegan, Meaghean C; Baxter, Leilan R; Maul, Jonathan D; Hanson, Mark L; Hoekstra, Paul F

2017-10-01

Thiamethoxam is a neonicotinoid insecticide used widely in agriculture to control a broad spectrum of chewing and sucking insect pests. Recent detection of thiamethoxam in surface waters has raised interest in characterizing the potential impacts of this insecticide to aquatic organisms. We report the results of toxicity testing (acute and chronic) conducted under good laboratory practices for more than 30 freshwater species (insects, molluscs, crustaceans, algae, macrophytes, and fish) and 4 marine species (an alga, a mollusc, a crustacean, and a fish). As would be anticipated for a neonicotinoid, aquatic primary producers and fish were the least sensitive organisms tested, with acute median lethal and effect concentrations (LC50/EC50) observed to be ≥80 mg/L in all cases, which far exceeds surface water exposure concentrations. Tested molluscs, worms, and rotifers were similarly insensitive (EC50 ≥ 100 mg/L), except for Lumbriculus sp., with an EC50 of 7.7 mg/L. In general, insects were the most sensitive group in the study, with most acute EC50 values insects (acute EC50 insects (EC50 > 5.5 mg/L). The most sensitive chronic response was for Chironomus riparius, with a 30-d no-observed-effect concentration (NOEC; emergence) of 0.01 mg/L. Observed toxicity to the tested marine organisms was comparable to that of freshwater species. We used the reported data to construct species sensitivity distributions for thiamethoxam, to calculate 5% hazard concentrations (HC5s) for acute data (freshwater invertebrates), and compared these with measured concentrations from relevant North American surface waters. Overall, based on acute toxicity endpoints, the potential acute risk to freshwater organisms was found to be minimal (likelihood of exceeding HC5s < 1%). Environ Toxicol Chem 2017;36:2838-2848. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental

Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

Science.gov (United States)

Nam, I. F.; Zhuk, V. V.

2015-04-01

Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

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Ying-Mei Niu

2016-01-01

Full Text Available We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n=60. Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P<0.05 at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P<0.05 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P<0.05 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity.

The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer

International Nuclear Information System (INIS)

Baglan, Kathy L.; Frazier, Robert C.; Yan Di; Huang, Raywin R.; Martinez, Alvaro A.; Robertson, John M.

2002-01-01

Purpose: A direct relationship between the volume of small bowel irradiated and the degree of acute small bowel toxicity experienced during concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy for rectal carcinoma is well recognized but poorly quantified. This study uses three-dimensional treatment-planning tools to more precisely quantify this dose-volume relationship. Methods and Materials: Forty patients receiving concurrent 5-FU-based chemotherapy and pelvic irradiation for rectal carcinoma had treatment-planning CT scans with small bowel contrast. A median isocentric dose of 50.4 Gy was delivered using a posterior-anterior and opposed lateral field arrangement. Bowel exclusion techniques were routinely used, including prone treatment position on a vacuum bag cradle to allow anterior displacement of the abdominal contents and bladder distension. Individual loops of small bowel were contoured on each slice of the planning CT scan, and a small bowel dose-volume histogram was generated for the initial pelvis field receiving 45 Gy. The volume of small bowel receiving each dose between 5 and 40 Gy was recorded at 5-Gy intervals. Results: Ten patients (25%) experienced Common Toxicity Criteria Grade 3+ acute small bowel toxicity. A highly statistically significant association between the development of Grade 3+ acute small bowel toxicity and the volume of small bowel irradiated was found at each dose level. Specific dose-volume threshold levels were found, below which no Grade 3+ toxicity occurred and above which 50-60% of patients developed Grade 3+ toxicity. The volume of small bowel receiving at least 15 Gy (V 15 ) was strongly associated with the degree of toxicity. Univariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicity. Conclusions: A strong dose-volume relationship exists for the development of Grade 3+ acute small bowel toxicity in patients receiving concurrent 5-FU-based chemoradiotherapy

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

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Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull. 2007; 6(4: 227-232

Investigation of Acute Toxicity of a Chemical Warfare Agent in Kidneys

Directory of Open Access Journals (Sweden)

Turgut Topal

2007-08-01

Full Text Available One of the most important chemical warfare agents, sulfur mustard (SM causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO and peroxynitrite are involved in nitrogen mustard (NM induced kidney damage. In this experimen, aminoguanidine (AG as inducible nitric oxide synthase (iNOS inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM. [TAF Prev Med Bull 2007; 6(4.000: 227-232

Effects of Malathion Acute Toxicity on Behavioral and Haematological Parameters in Capoeta damascina (Cypriniformes: Cyprinidae

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Saeed Shahbazi

2015-07-01

Full Text Available   The present study investigated the effects of acute toxicity of malathion on behavioral and haematological parameters in the cyprinid Capoeta damascina. The specimens were collected from the Kordan River, Karaj, Iran in August, 2014 and were exposed to different concentrations of malathion at the laboratory (24, 48, 72 mg L‑1 based on 96h-LC (10; 30; 50; 90 which was 6.08 (5.22-7.18 mg L-1. The animals were then exposed to 0.76, 1.00 and 1.52 mg L-1 of malathion for 10 days. Blood samples were collected in days 1, 5 and 10. Red blood cell (RBC, white blood cell (WBC, hemoglobin (Hb, hematocrit (PVC, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, and mean corpuscular hemoglobin concentration (MCHC were measured. Behavioral abnormalities were observed in fishes exposed to high levels of malathion. The specimens exposed to malathion had significantly lower RBC, WBC, Hb, PVC but higher MCV and MCH than those of the control group. No significant difference was detected in MCHC the exposed and control specimens. Hematological parameters (except MCHC were significantly correlated with exposure time. In conclusion, malathion showed extensive haematological effects on C. damascina that might be used as bioindicator of this pesticide in flowing waters.  

Combined anaerobic–ozonation process for treatment of textile wastewater: Removal of acute toxicity and mutagenicity

Energy Technology Data Exchange (ETDEWEB)

Punzi, Marisa, E-mail: marisa.punzi@biotek.lu.se [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Nilsson, Filip [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Anbalagan, Anbarasan [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Svensson, Britt-Marie [School of Education and Environment, Kristianstad University, SE-291 88 Kristianstad (Sweden); Jönsson, Karin [Water and Environmental Engineering at the Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); Mattiasson, Bo; Jonstrup, Maria [Department of Biotechnology, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden)

2015-07-15

Highlights: • COD and UV absorbance were effectively reduced. • The treated effluents were non-toxic to Artemia salina and Vibrio fischeri. • The real textile wastewater was mutagenic. • Mutagenicity persisted after bio treatment and even more after a short ozonation. • Higher ozone doses completely remove mutagenicity. - Abstract: A novel set up composed of an anaerobic biofilm reactor followed by ozonation was used for treatment of artificial and real textile effluents containing azo dyes. The biological treatment efficiently removed chemical oxygen demand and color. Ozonation further reduced the organic content of the effluents and was very important for the degradation of aromatic compounds, as shown by the reduction of UV absorbance. The acute toxicity toward Vibrio fischeri and the shrimp Artemia salina increased after the biological treatment. No toxicity was detected after ozonation with the exception of the synthetic effluent containing the highest concentration, 1 g/l, of the azo dye Remazol Red. Both untreated and biologically treated textile effluents were found to have mutagenic effects. The mutagenicity increased even further after 1 min of ozonation. No mutagenicity was however detected in the effluents subjected to longer exposure to ozone. The results of this study suggest that the use of ozonation as short post-treatment after a biological process can be beneficial for the degradation of recalcitrant compounds and the removal of toxicity of textile wastewater. However, monitoring of toxicity and especially mutagenicity is crucial and should always be used to assess the success of a treatment strategy.

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

Science.gov (United States)

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

2018-01-23

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

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

Science.gov (United States)

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

2015-03-27

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

Directory of Open Access Journals (Sweden)

Olga Zhuk

2015-03-01

Full Text Available The pharmacological activities and acute toxicity of the psilocin (PC and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS, indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR, was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP induced spontaneous head-twitching in mice (100% effect, as a result of the formation of 5-hydroxytryptamine (5-HT in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Development of thresholds of excess toxicity for environmental species and their application to identification of modes of acute toxic action.