Science.gov

Sample records for chronic toxicity studies

  1. ACUTE AND CHRONIC TOXICITY STUDIES WITH MONOCHLOROBENZENE IN RAINBOW TROUT

    EPA Science Inventory

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity was monitored...

  2. Chronic toxicity study of neosaxitoxin in rats.

    PubMed

    Zepeda, Ramiro J; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F

    2014-09-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  3. Chronic Toxicity Study of Neosaxitoxin in Rats

    PubMed Central

    Zepeda, Ramiro J.; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F.

    2014-01-01

    Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. PMID:25257789

  4. Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

    USGS Publications Warehouse

    Dahlich, G.M.; Larson, R.E.; Gingerich, W.H.

    1982-01-01

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity. Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish. The LC50 of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.

  5. Critical appraisal of the duration of chronic animal toxicity studies

    SciTech Connect

    Lumley, C.E.; Walker, S.R.

    1986-03-01

    One method of assessing the contribution of studies of longer than 6 months to a safety evaluation program is to compare retrospectively the findings in toxicity tests carried out for 6 months or less with those observed after 6 months. The Center for Medicines Research has therefore established a databank comprising animal toxicological data obtained from pharmaceutical companies in Europe. Twenty-one companies have provided data for 124 compounds (214 studies), including 88 studies of 65 compounds where comparable short-term (less than or equal to 6 months) and long-term (greater than 6 months) data are available. The results from the 88 studies show that, excluding the possibility of identifying carcinogens, tests of longer than 6 months have not added to the overall safety evaluation of these compounds.

  6. Chronic toxicity, reproductive, and teratogenic studies of hexazinone.

    PubMed

    Kennedy, G L; Kaplan, A M

    1984-12-01

    Hexazinone [3-cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-triazine 2,4(1H,3H)-dione; CAS 51235-04-2] was tested for oral toxicity in rats (both 90-day and 2-year feeding studies), mice (8-week and 2-year feeding studies), and dogs (90-day feeding study). The teratogenic potential was evaluated in rabbits and rats and functional reproductive capacity was studied in rats. Ninety-day feeding of up to 1000 ppm produced no signs of a toxic response in rats. Rats fed 5000 ppm had growth curves slightly inferior to those of the controls as the only detectable difference. Extending the feeding period to 2 years produced decreased body weights in males fed 2500 ppm (top level tested) and in females fed either 1000 or 2500 ppm. All other indices of response, including the type and distribution of tumors, were similar in the test and control rats with the no-effect level being 200 ppm. Eight-week feeding of up to 10,000 ppm in mice produced increased liver weight only at the highest level without any other changes. Two-year feeding of either 200, 2500, or 10,000 ppm resulted in sloughing of the distal tip of the tail and increased liver weights among mice fed 10,000 ppm. Hypertrophy of centrilobular hepatocytes and hyperplasic nodules were increased in mice fed either 2500 or 10,000 ppm. No evidence of a tumorigenic response was evident. The no-effect level was 200 ppm. Dogs fed 5000 ppm for 90 days had decreased rate of body weight gain with clinical enzyme changes suggestive of liver damage. Microscopic examination of the liver failed to reveal any alterations and dogs fed either 200 or 1000 ppm were indistinguishable from controls. The no-effect level in the dog was 1000 ppm. No evidence of a teratogenic response was seen in either rats or rabbits and reproduction capacity in rats fed up to 2500 ppm for three generations was unaffected. PMID:6519376

  7. Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations.

    PubMed

    Case, M T; Smith, J K; Nelson, R A

    Because of an apparent typographic error in a US patent, there has been some confusion as to the acute oral toxicity of danthron and danthron in combination with dioctyl sodium sulfosuccinate (DSS). Acute oral toxicity studies in mice revealed LD50 values of greater than 7 gm/kg for danthron, 2.64 gm/kg for DSS and 3.42 gm/kg for danthron/DSS mixture (1:2 ratio). These results indicate that the lethality of these compounds is in the gm/kg range and not in the mg/kg range. A one year chronic toxicity study of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations in dogs failed to reveal any toxic effects. In particular, there was no evidence of hepatotoxicity or of any changes in the myenteric plexuses in the chronically treated dogs. PMID:90594

  8. Challenging the requirement for chronic fish toxicity studies on formulated plant protection products.

    PubMed

    Creton, Stuart; Douglas, Mark; Wheeler, James R; Hutchinson, Thomas H

    2010-11-30

    Ecotoxicity testing of pesticide active ingredients and formulated plant protection products (PPPs) prior to their commercial use is required by authorities around the world. Such studies are important for the conduct of risk assessments to protect wildlife and the environment, but they should only be conducted when their use is scientifically justified. One test of questionable scientific merit is the chronic fish toxicity test when conducted with formulated PPPs, which is a potential requirement under European legislation: chronic exposure to the formulated product per se rarely occurs in the environment and therefore it is generally not possible to use the data from chronic formulation studies in a meaningful risk assessment. A recent survey of European crop protection companies to explore the scientific merits and regulatory drivers for chronic fish toxicity studies has shown that current practice in deciding on the need for chronic fish toxicity testing of formulated PPPs varies substantially between companies. The most commonly cited reason for conducting such studies was solely to meet regulatory requirements. We conclude that chronic formulation testing is rarely if ever scientifically justified, and recommend that the forthcoming revision of the EU Aquatic Toxicology Guidance Document takes account of this by including a requirement that justification must be provided for conducting the test, rather than the current situation where the onus is on the registrant to provide a justification for not conducting the test. PMID:20832457

  9. Toxicity Studies.

    PubMed

    2016-01-01

    Toxicity studies in the animal models are done to determine the dose level recommended for the treatment of disease as drug. This guideline enables the characterization of adverse effects following repeated daily inhalation exposure to a test. This chapter includes oral and dermal toxicity studies which are discussed as per OECD guidelines. Both acute and subacute toxicity studies are given special emphasis. PMID:26939270

  10. An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program.

    PubMed Central

    Chhabra, R S; Huff, J E; Schwetz, B S; Selkirk, J

    1990-01-01

    Since the establishment of the National Toxicology Program (NTP), there have been gradual changes in strategies to evaluate the overall toxicity of chemicals as well as their carcinogenic potential. The spectrum of toxicologic information sought on selected chemicals has been broadened by the multidisciplinary approach to evaluating chemicals. This paper describes the scientific rationale and experimental processes used by NTP in designing studies. Also, an outline of current NTP protocols are given for prechronic and chronic toxicity/carcinogenicity studies. PMID:2205492

  11. Chronic dietary toxicity and carcinogenicity study with ammonium perfluorooctanoate in Sprague-Dawley rats.

    PubMed

    Butenhoff, John L; Kennedy, Gerald L; Chang, Shu-Ching; Olsen, Geary W

    2012-08-16

    In order to assess the potential chronic toxicity and tumorigenicity of ammonium perfluorooctanoate (APFO), a 2-year dietary study was conducted with male and female rats fed 30 ppm or 300 ppm (approximately 1.5 and 15 mg/kg). In males fed 300 ppm, mean body weights were lower across most of the test period and survival in these rats was greater than that seen either in the 30 ppm or the control group. Non-neoplastic effects were observed in liver in rats fed 300 ppm and included elevated liver weight, an increase in the incidence of diffuse hepatocellular hypertrophy, portal mononuclear cell infiltration, and mild hepatocellular vacuolation without an increase in hepatocellular necrosis. Mean serum activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were elevated up to three times the control means, primarily at the 300 ppm dose. A significant increase in Leydig cell tumors of the testes was seen in the males fed 300 ppm, and tumors of the liver and acinar pancreas, which are often observed in rats from chronic exposure to peroxisome proliferating agents, were not observed in this study. All other tumor types were those seen spontaneously in rats of this stock and age and were not associated with feeding of APFO. PMID:22531602

  12. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Chronic toxicity. 798.3260 Section 798.3260 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Chronic Exposure § 798.3260 Chronic toxicity. (a) Purpose. The objective of a chronic...

  13. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  14. Issues in the Design and Interpretation of Chronic Toxicity and Carcinogenicity Studies in Rodents: Approaches to Dose Selection

    EPA Science Inventory

    For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has ...

  15. Acute, sub-chronic oral toxicity studies and evaluation of antiulcer activity of Sooktyn in experimental animals

    PubMed Central

    Chandra, Phool; Sachan, Neetu; Kishore, Kamal; Ghosh, Ashoke Kumar

    2012-01-01

    Sooktyn (SKN), mineralo-herbal drug which is being used largely by the patients for its extremely good therapeutic value to treat the gastric ulcers. The present study was undertaken to evaluate the toxicity studies and antiulcer activity of SKN. Acute and sub-chronic toxicities were studied in male and female Wistar rats. A single acute SKN of 2 000 mg/kg was administered by oral gavage for acute toxicity. Sub-chronic doses were 400 and 800 mg/kg/day. The major toxicological end points examined included animal body weight and food intake, selected tissue weights, and detailed gross necropsy. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total leukocyte count and MCH, MCHC and platelets as well as biochemical parameters: urea, sugar, alanine transaminase, aspartate transaminase, alkaline phosphatase, total proteins, and creatinine. Also, anti-ulcer activity was carried out by employing indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models. LD50 may be greater than 2 000 mg/kg (orally) for SKN and there were no signs of toxicity on 28 days sub-chronic oral administration of 400 and 800 mg/kg of SKN in rats on the basis of blood elements and biochemical parameters. The ulcer indices decrease in all ulcer models with 66.62%, 61.24%, 80.18%, and 74.76% in indomethacin, ethanol, pylorus ligation, and hypothermic-stress-induced ulcer models, respectively. The results suggest that SKN has no signs of toxicity at 2 000 mg/kg body weight of rats orally; sub-chronically. The drug is safe and has antiulcer activity. PMID:22837960

  16. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

    PubMed

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder

  17. Acute and chronic toxicity of chromium and cadmium to the tropical cladoceran pseudosida ramosa and the implications for ecotoxicological studies.

    PubMed

    Freitas, Emanuela Cristina; Rocha, Odete

    2014-02-01

    In this study, the acute and chronic toxicity of the metals chromium and cadmium were tested against the tropical freshwater cladoceran Pseudosida ramosa. Acute tests showed that the 48-h LC50 of chromium was 29 μg L(-1) , while that of cadmium was 12 μg L(-1) . P. ramosa had a similar sensitivity to those of other cladoceran species cultured in the same conditions as in this study, or a higher sensitivity when water hardness was raised. Long-term chronic exposure of P. ramosa to chromium decreased maternal survival, fecundity, and fertility at a concentration of 10 μg L(-1) . For cadmium, reductions in the same endpoints were observed at a concentration of 3 μg L(-1) . Moreover, the degree of toxicity of the chromium and cadmium to P. ramosa after release of the first brood was similar to the result obtained after 21 days, using reproduction as the endpoint. Brazilian water bodies located near industrial areas already show concentrations of chromium and cadmium higher than levels causing acute and chronic toxicity to P. ramosa in our study. Many water quality criteria in tropical regions are based on ecotoxicological tests with non-native species and, consequently, this may lead to errors of interpretation when the permitted maximum levels of for each toxic substance are established. Therefore, we reinforce the idea of using native species to establish the maximum concentrations of toxic substances in water quality criteria, especially for metals, since their effects are related to water hardness, pH, and temperature specific to each region. PMID:22038926

  18. Sub-chronic toxicity study in rats orally exposed to nanostructured silica

    PubMed Central

    2014-01-01

    Background Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5 – 200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica. Methods Rats were orally exposed to 100, 1000 or 2500 mg/kg bw/day of SAS, or to 100, 500 or 1000 mg/kg bw/day of NM-202 (a representative nanostructured silica for OECD testing) for 28 days, or to the highest dose of SAS or NM-202 for 84 days. Results SAS and NM-202 were extensively characterized as pristine materials, but also in the feed matrix and gut content of the animals, and after in vitro digestion. The latter indicated that the intestinal content of the mid/high-dose groups had stronger gel-like properties than the low-dose groups, implying low gelation and high bioaccessibility of silica in the human intestine at realistic consumer exposure levels. Exposure to SAS or NM-202 did not result in clearly elevated tissue silica levels after 28-days of exposure. However, after 84-days of exposure to SAS, but not to NM-202, silica accumulated in the spleen. Biochemical and immunological markers in blood and isolated cells did not indicate toxicity, but histopathological analysis, showed an increased incidence of liver fibrosis after 84-days of exposure, which only reached significance in the NM-202 treated animals. This observation was accompanied by a moderate, but significant increase in the expression of fibrosis-related genes in liver samples. Conclusions Although only few adverse effects were observed, additional studies are warranted to further evaluate the biological relevance of observed fibrosis in liver and possible accumulation of silica in the spleen in the NM-202

  19. Chronic toxicity of biphenyl to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Bartlett, E.A.; Murphy, P.G.; Milazzo, D.P. )

    1989-09-01

    The US Environmental Protection Agency (EPA) issued a final test rule (1985) for biphenyl on the authority of Section 4(a) of the Toxic Substances Control Act (TSCA). Contained within this rule was the requirement for generating chronic daphnid toxicity data for biphenyl. Biphenyl is used primarily to produce dye carriers, heat-transfer fluids and alkylated biphenyls. The acute toxicity of biphenyl to Daphnia magna has been reported. The 48-hr LC50 values were 4.7 and 2.1 mg/L, respectively. To date, the chronic toxicity of biphenyl to fish and aquatic invertebrates has not been investigated. The objective of this study was to determine the chronic toxicity of biphenyl to D. magna. The daphnid chronic toxicity test is designed to estimate the maximum acceptable toxicant concentration (MATC). The MATC is defined as the concentration falling between the highest concentration showing no effect and the next higher concentration showing a toxic effect when compared to the controls.

  20. NMR-based metabolomics approach to study the chronic toxicity of crude ricin from castor bean kernels on rats.

    PubMed

    Guo, Pingping; Wang, Junsong; Dong, Ge; Wei, Dandan; Li, Minghui; Yang, Minghua; Kong, Lingyi

    2014-07-29

    Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM. PMID:24992468

  1. Ranking chemicals based on chronic toxicity data.

    PubMed

    De Rosa, C T; Stara, J F; Durkin, P R

    1985-12-01

    During the past 3 years, EPA's ECAO/Cincinnati has developed a method to rank chemicals based on chronic toxicity data. This ranking system reflects two primary attributes of every chemical: the minimum effective dose and the type of effect elicited at that dose. The purpose for developing this chronic toxicity ranking system was to provide the EPA with the technical background required to adjust the RQs of hazardous substances designated in Section 101(14) of CERCLA or "Superfund." This approach may have applications to other areas of interest to the EPA and other regulatory agencies where ranking of chemicals based on chronic toxicity is desired. PMID:3843499

  2. A chronic toxicity study of the ground root bark of Capparis erythrocarpus (Cappareceae) in male Sprague-Dawley rats.

    PubMed

    Martey, O N K; Armah, G E; Sittie, A A; Okine, L K N

    2013-12-01

    The safety evaluation of Capparis erythrocarpus (CE) on chronic administration at 18 and 180 mg kg(-1) body weight for 6 months was investigated in male Sprague-Dawley rats. The effects of CE on certain serum biochemical, haematological, urine and histopathological determinations were used as indices of organ specific toxicity. Also the effects of CE on rat blood clotting time and pentobarbital-induced sleeping time were determined. Results indicate that CE had no effect on urine, haematological and serum biochemical indices at termination of treatment with the exception of serum ALT level which was significantly (p < 0.05) attenuated in a dose-dependent fashion (21-35%). There were also no differences in blood clotting time and pentobarbital-induced sleeping time between CE-treated and control animals. Histopathological studies showed that CE did not adversely affect the morphology of the liver, kidney and heart tissues. However, lungs of CE-treated animals showed slight but insignificant inflammatory response in alveolar areas and Clara cell hyperplasia without the thickening of alveolar septa and bronchiolar epithelial wall. Organ weights were not adversely affected by CE treatment. There were significant (p < 0.05) changes in weight of CE-treated animals with duration of treatment compared to control. These results suggest that there is no organ specific toxicity associated with chronic administration of CE in rats and its ability to reduce body weight may be useful for slimming in obese persons. PMID:24506037

  3. Application of metabolomics to toxicology of drugs of abuse: A mini review of metabolomics approach to acute and chronic toxicity studies.

    PubMed

    Zaitsu, Kei; Hayashi, Yumi; Kusano, Maiko; Tsuchihashi, Hitoshi; Ishii, Akira

    2016-02-01

    Metabolomics has been widely applied to toxicological fields, especially to elucidate the mechanism of action of toxicity. In this review, metabolomics application with focus on the studies of chronic and acute toxicities of drugs of abuse like stimulants, opioids and the recently-distributed designer drugs will be presented in addition to an outline of basic analytical techniques used in metabolomics. Limitation of metabolomics studies and future perspectives will be also provided. PMID:26613805

  4. Measuring chronic toxicity using luminescent bacteria

    SciTech Connect

    Huynh, H.; Bulich, A.

    1994-12-31

    Bioassays using luminescent bacteria are routinely used to assess the acute toxicity of environmental samples. Two physiological characteristics of these test organisms, a short division cycle and the inducible luciferase pathway, provide functional attributes for measuring chronic toxicity. Freeze-dried luminescent bacteria, following inoculation into appropriate growth medium, initiate a series of reproductive cycles while inducing a complex series of metabolic pathways resulting in production of bioluminescence. Toxic chemicals or samples which inhibit any aspect of this reproductive cycle or induction of light production are detected in low concentrations. The development of this bioassay is based upon a detailed understanding of the growth requirements and biochemistry of this organism and the genetics of luciferase induction. A defined growth medium was developed which supports the necessary cell growth and luciferase induction, yet which does not mask the presence of toxic substances. To perform the assay, the test organisms are inoculated into a series of cuvettes containing growth medium and dilutions of the sample. After 18 hrs incubation at 27 C, control cuvettes show high light levels while sample dilutions containing toxic materials show decreasing light levels. Details of the test protocol and reproducibility are presented. Sensitivity data from this chronic toxicity test are summarized and compared with the Microtox{reg_sign} acute test and the Ceriodaphnia dubia chronic toxicity test method. This test method is about 20 times more sensitive than Microtox and exhibits sensitivity similar to C. dubia for tested metals and organic compounds.

  5. Anti-atherogenic and anti-ischemic potentials of Croton membranaceus observed during sub-chronic toxicity studies

    PubMed Central

    Afriyie, Dan K.; Asare, George A.; Bugyei, Kwasi; Asiedu-Gyekye, Isaac; Gyan, Ben A.; Adjei, Samuel; Addo, Phyllis; Sittie, Archibald; Nyarko, Alexander K.

    2013-01-01

    Background: Croton membranaceus (CM) is used for benign prostate hyperplasia treatment. Objective: Sub-chronic toxicity studies are non-existent and provided the basis for this study. Materials and Methods: 90 days oral administration of a low dose (LD) (30 mg/kg b. wt.), medium dose (MD) (150 mg/kg b. wt.), and high dose (HD) (300 mg/kg b. wt.) CM aqueous root extract to 3 groups (n=6 each) of male Sprague-Dawley rats, alongside a control group, was undertaken. Urinalysis, hepato-renal function tests, lipid profile, cardiac enzymes, and routine hematology tests were performed. Results: Triglyceride levels (C=1.05±0.19, LD=0.64±0.08, MD=0.55±0.04, HD=0.50±0.02 mmol/L) were significantly reduced (P<0.05). Very low density lipoprotein (C=0.48±0.09, LD=0.29±0.04, MD=0.25±0.02, HD=0.23±0.01 mmol/L) decreased significantly (P<0.05). Cardiac enzymes-creatinine kinase (C=568±172, LD=315±79, MD=441±209, HD=286±81 IU/L) decreased markedly (P<0.05) alongside lactate dehydrogenase (C=2675±875, LD=1667±1229, MD=1186±442, HD=855±239 IU/L) (P<0.05). Conclusion: C. membranaceus aqueous root extract is non-toxic but demonstrates anti-atherogenic and anti-ischemic potentials. PMID:23598919

  6. A combined dietary chronic toxicity and two-year carcinogenicity study of (2R,4R)-monatin salt in Sprague-Dawley rats.

    PubMed

    Brathwaite, Witty A; Crincoli, Christine M; Eapen, Alex K; Rihner, Marisa O; Nikiforov, Andrey I; Remick, Amera K

    2016-05-01

    In a combined chronic toxicity/carcinogenicity study, groups of Crl:CD(SD) rats were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm (2R,4R)-monatin salt (hereafter "R,R-monatin") in the diet for up to one year in the chronic toxicity phase and up to two years in the carcinogenicity phase. There were no adverse effects on survival, incidence of palpable masses, neoplasms, organ weights, or ophthalmic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups generally throughout the study, which were most likely a result of caloric dilution of the test diets. Effects of long-term R,R-monatin ingestion by rats were predominantly focused on the urinary system (i.e., clinical pathology alterations indicative of electrolyte and pH imbalances, increased incidence of renal calculi, mineralization and bone hyperostosis, and increased severity of chronic progressive nephropathy). The no-observed-adverse-effect level (NOAEL) for R,R-monatin from the chronic toxicity phase was 20,000 ppm (equivalent to an exposure level of 1080 mg/kg bw/day for males and 1425 mg/kg/day for females) and from the carcinogenicity phase was 5000 ppm (equivalent to an exposure level of 238 and 302 mg/kg bw/day for males and females, respectively). PMID:26747978

  7. 40 CFR 798.3320 - Combined chronic toxicity/oncogenicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Combined chronic toxicity/oncogenicity. 798.3320 Section 798.3320 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Chronic Exposure § 798.3320 Combined chronic toxicity/oncogenicity....

  8. Chronic fatigue syndrome following a toxic exposure.

    PubMed

    Racciatti, D; Vecchiet, J; Ceccomancini, A; Ricci, F; Pizzigallo, E

    2001-04-10

    Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS. PMID:11327394

  9. A Chronic Oral Toxicity Study of Marine Collagen Peptides Preparation from Chum Salmon (Oncorhynchus keta) Skin Using Sprague-Dawley Rat

    PubMed Central

    Liang, Jiang; Pei, Xin-Rong; Zhang, Zhao-Feng; Wang, Nan; Wang, Jun-Bo; Li, Yong

    2011-01-01

    Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet. PMID:22363218

  10. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Daphnid chronic toxicity test. 797.1330 Section 797.1330 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1330 Daphnid chronic toxicity test. (a) Purpose....

  11. Chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Milazzo, D.P.

    1988-01-01

    Data generated from daphnid chronic toxicity tests are used by various regulatory agencies for the development of water quality criteria. Two chemicals which are lacking reported chronic data are aniline and 2,4-dichlorophenol. The acute toxicity of 2,4-dichlorophenol to Daphnia magna has been reported; the toxicity of aniline to D. magna also has been reported. Chronic data for these chemicals are lacking for invertebrates. The objective of this study was to estimate the chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus, using a standard 21-day static renewal procedure.

  12. Psychologic sequelae of chronic toxic waste exposure

    SciTech Connect

    Foulks, E.; McLellen, T. )

    1992-02-01

    Exposure to toxic industrial substances has been a topic of increasing concern to environmentalists, government agencies, industrial engineers, and medical specialists. Our study focuses on the psychologic symptom responses of a community to perceived long-term exposure to toxic waste products. We compared their symptom clusters, as shown by their responses to questions on the Hopkins Symptom Checklist-90 Item (SCL-90) and the Social Adjustment Scale (SAS), with symptom levels of normal and depressed subjects. Issues of media coverage, litigation, and potential for compensation complicate the psychiatric epidemiology of the subject.

  13. Relationship Between Radiation-Induced Apoptosis of T Lymphocytes and Chronic Toxicity in Patients With Prostate Cancer Treated by Radiation Therapy: A Prospective Study

    SciTech Connect

    Foro, Palmira; Algara, Manuel; Lozano, Joan; Rodriguez, Nuria; Sanz, Xavier; Torres, Erica; Carles, Joan; Reig, Anna; Membrive, Ismael; Quera, Jaume; Fernandez-Velilla, Enric; Pera, Oscar; Lacruz, Marti; Bellosillo, Beatriz

    2014-04-01

    Purpose: To assess the correlation of radiation-induced apoptosis in vitro of CD4 and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with radiation therapy. Methods and Materials: 214 patients were prospectively included in the study. Peripheral blood was drawn from patients before treatment and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity and mortality were correlated in 198 cases with pretreatment apoptosis and clinical and biological variables by use of a Cox proportional hazards model. Results: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced apoptosis was 28.58% (±14.23) and 50.76% (±18.9), respectively. Genitourinary (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI) toxicity was experienced by 19.7%. The probability of development of GU toxicity was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was ≤28.58%. It was also almost double in patients who received doses ≥50 Gy in 65% of the bladder volume (V65 ≥50) (HR 1.92, P=.048). No correlation was found between GI toxicity and any of the variables studied. The probability of death during follow-up, after adjustment for different variables, was 2.7 times higher in patients with a percentage of CD8+ T lymphocyte apoptosis ≤50.76% (P=.022). Conclusions: In conclusion, our study shows, in the largest prospective cohort of prostate cancer patients undergoing radiation therapy, that in vitro radiation-induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was associated with the probability of developing chronic GU toxicity. In addition, the radiation dose received in the urinary bladder (V65 ≥50) affected the occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced apoptosis of

  14. Chronic toxicity evaluation of simulated DWPF effluent to Ceriodaphnia dubia

    SciTech Connect

    Not Available

    1990-04-01

    A 7-Day Full Series Chronic Toxicity test was conducted April 13--20, 1990, for the Savannah River Site to assess the chronic toxicity of Simulated defense waste processing facility (DWPF) effluent to Ceriodaphnia dubia. The simulated effluented consisted of Sodium Nitrate, Sodium Oxalate, Sodium Formate, and Corros. Inib.

  15. CHRONIC TOXICITY OF AMMONIA OF RAINBOW TROUT

    EPA Science Inventory

    The chronic effects of ammonia to rainbow trout Salmo gairdneri were studied in a laboratory test conducted over a 5-year period. Fish were tested at five concentrations over the range 0.01-0.07 mg/liter un-ionized ammonia; the mean pH of the test water was 7.7, and the mean temp...

  16. Influence of genetic composition of test-animal populations on chronic toxicity studies used for risk estimation.

    PubMed

    Littlefield, N A; Wolff, G L; Nelson, C J

    1985-01-01

    A lifespan exposure of mice to benzidine dihydrochloride was conducted for 33 m using both sexes of two populations of mice with the same gene pool. One population was the genetically homogeneous F1 hybrid produced by crossing BALB/cStCrlC3Hf/Nctr males with C57BL/6jfC3Hf/Nctr females. The second population consisted of genetically heterogenous monohybrid cross (MC) offspring produced by mating the F1 hybrids inter se. Data comparisons were made to determine if gene distribution among members of a population affects the response to a toxic insult. Endpoints tested consisted of mortality, liver tumor incidence and time of tumor onset, mortality from reticulum-cell sarcoma, and body weights. In most instances it was noted that among animals not dosed (controls), the F1 population had lower background incidence of lesions and lived longer than the MC population. However, among the dosed animals, the F1 mice were generally more susceptible to the toxic agent and developed higher incidences of the chemically induced lesions than did the MC population. The F1 hybrid population gave a more conservative estimate of risk than did the MC population. The calculation of the liver tumor risk for these two populations showed that lifespan exposure to benzidine would be predicted to result in a larger number (higher risk) when using the F1 data. A 4.5-fold difference in the toxic response was observed between the F1 females and the MC males. This emphasizes the importance of gene distribution in risk estimation studies. PMID:4032486

  17. Influence of genetic composition of test-animal populations on chronic toxicity studies used for risk estimation

    SciTech Connect

    Littlefield, N.A.; Wolff, G.L.; Nelson, C.J.

    1985-01-01

    A lifespan exposure of mice to benzidine dihydrochloride was conducted for 33 m using both sexes of two populations of mice with the same gene pool. One population was the genetically homogeneous F/sub 1/ hybrid produced by crossing BALB/cStCrlC3Hf/Nctr males with C57BL/6JfC3Hf/Nctr females. The second population consisted of genetically heterogenous monohybrid cross (MC) offspring produced by mating the F/sub 1/ hybrids inter se. Data comparisons were made to determine if gene distribution among members of a population affects the response to a toxic insult. Endpoints tested consisted of mortality, liver tumor incidence and time of tumor onset, mortality from reticulum-cell sarcoma, and body weights. In most instances it was noted that among animals not dosed (controls), the F/sub 1/ population has lower background incidence of lesions and lived longer than the MC population. However, among the dosed animals, the F/sub 1/ mice were generally more susceptible to the toxic agent and developed higher incidences of the chemically induced lesions than did the MC population. The F/sub 1/ hybrid population gave a more conservative estimate of risk than did the MC population. The calculation of the liver tumor risk for these two populations showed that lifespan, exposure to benzidine would be predicted to result in a larger number (higher risk) when using the F/sub 1/ data. A 4.5-fold difference in the toxic response was observed between the F/sub 1/ females and the MC males. This emphasizes the importance of gene distribution in risk estimation studies.

  18. Aluminium toxicity in chronic renal insufficiency

    SciTech Connect

    Savory, J.; Bertholf, R.L.; Wills, M.R.

    1985-08-01

    Aluminium is a ubiquitous element in the environment and has been demonstrated to be toxic, especially in individuals with impaired renal function. Not much is known about the biochemistry of aluminium and the mechanisms of its toxic effects. Most of the interest in aluminium has been in the clinical setting of the hemodialysis unit. Here aluminium toxicity occurs due to contamination of dialysis solutions, and treatment of the patients with aluminium-containing phosphate binding gels. Aluminium has been shown to be the major contributor to the dialysis encephalopathy syndrome and an osteomalacic component of dialysis osteodystrophy. Other clinical disturbances associated with aluminium toxicity are a microcytic anemia and metastatic extraskeletal calcification. Aluminium overload can be treated effectively by chelation therapy with desferrioxamine and hemodialysis. Aluminium is readily transferred from the dialysate to the patient's -bloodstream during hemodialysis. Once transferred, the aluminium is tightly bound to non-dialysable plasma constituents. Very low concentrations of dialysate aluminium in the range of 10-15 micrograms/l are recommended to guard against toxic effects. Very few studies have been directed towards the separation of the various plasma species which bind eluminium. Gel filtration chromatography has been used to identify five major fractions, one of which is of low molecular weight and the others appear to be protein-aluminium complexes. Recommendations on aluminium monitoring have been published and provide safe and toxic concentrations. Also, the frequency of monitoring has been addressed. Major problems exist with the analytical methods for measuring aluminium which result from inaccurate techniques and contamination difficulties. 136 references.

  19. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice

    PubMed Central

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. PMID:26785375

  20. Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice.

    PubMed

    Zhang, Jia-Qing; Gao, Bin-Wen; Wang, Jing; Wang, Xian-Wei; Ren, Qiao-Ling; Chen, Jun-Feng; Ma, Qiang; Xing, Bao-Song

    2016-01-01

    Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals. PMID:26785375

  1. Prognostic Utility of Serum Potassium in Chronic Digoxin Toxicity

    PubMed Central

    Manini, Alex F.; Nelson, Lewis S.; Hoffman, Robert S.

    2016-01-01

    Objective In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. Methods This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000–2006) versus survivors (controls) over a 1-year period (2007–2008). Results During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0 mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. Conclusion In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration. PMID:21619380

  2. Aqueous extract of Senecio candicans DC induce liver and kidney damage in a sub-chronic oral toxicity study in Wistar rats.

    PubMed

    Lakshmanan, Hariprasath; Raman, Jegadeesh; Pandian, Arjun; Kuppamuthu, Kumaresan; Nanjian, Raaman; Sabaratam, Vikineswary; Naidu, Murali

    2016-08-01

    Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P < 0.05) in serum uric acid, creatinine, aspartate transaminase (AST) and alanine transaminase (ALP) levels. Histological examination of liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use

  3. Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    EPA Science Inventory

    The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

  4. Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents.

    PubMed

    Akindele, Abidemi J; Adeneye, Adejuwon A; Salau, Oluwole S; Sofidiya, Margaret O; Benebo, Adokiye S

    2014-01-01

    Flabellaria paniculata Cav. (Malpighiaceae) is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of F. paniculata (HLE-FP). HLE-FP was administered p.o. (20, 100, and 500 mg/kg) for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p < 0.05) reductions in weight gain pattern compared to control. These changes were sustained with 60 days treatment. However, no significant (p > 0.05) differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p < 0.05) increases in Hb, PCV and RBC on day 30 and significant (p < 0.05) increases in MCV and MCH indices on day 60 compared to control. There were significant (p < 0.05) elevations in serum K(+), urea and creatinine compared to control. The liver function tests showed slight but non-significant alterations in relevant parameters when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioral manifestations like restlessness, generalized body tremor, feed, and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution

  5. Acute and Chronic Toxicity, Cytochrome P450 Enzyme Inhibition, and hERG Channel Blockade Studies with a Polyherbal, Ayurvedic Formulation for Inflammation

    PubMed Central

    Dey, Debendranath; Chaskar, Sunetra; Athavale, Nitin; Chitre, Deepa

    2015-01-01

    Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005–1 mg/mL) by MTT/formazan method, an acute single dose (2–10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15–20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and 3H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use. PMID:25893199

  6. Acute and chronic toxicity, cytochrome p450 enzyme inhibition, and HERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation.

    PubMed

    Dey, Debendranath; Chaskar, Sunetra; Athavale, Nitin; Chitre, Deepa

    2015-01-01

    Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005-1 mg/mL) by MTT/formazan method, an acute single dose (2-10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15-20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and (3)H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use. PMID:25893199

  7. SITE-SPECIFIC VALIDATION OF A CHRONIC TOXICITY TEST WITH THE AMPHIPOD HYALELLA AZTECA : AN INTEGRATED STUDY OF HEAVY METAL CONTAMINATED SEDIMENTS IN PEAK CREEK, VIRGINIA

    EPA Science Inventory

    We will measure the correspondence of endpoints from chronic toxicity tests with the amphipod, Hyalella azteca, to a series of in situ macrobenthic community endpoints, starting with those endpoints most similar to those monitored in the laboratory test, then expanding to include...

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

    EPA Science Inventory

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

  9. Chronic toxicity of environmental contaminants: sentinels and biomarkers.

    PubMed Central

    LeBlanc, G A; Bain, L J

    1997-01-01

    Due to the use of a limited number of species and subchronic exposures, current ecological hazard assessment processes can underestimate the chronic toxicity of environmental contaminants resulting in adverse responses of sentinel species. Several incidences where sentinel species have responded to the effects of chronic exposure to ambient levels of environmental contaminants are discussed, including the development of neoplasia in fish, immunosuppression in marine mammals, pseudohermaphrodism in invertebrates, teratogenicity in amphibians, and aberrations in the sexual development of fish and reptiles. Biomarkers of chronic toxicity, including DNA mutations, alterations in specific protein and mRNA levels, and perturbations in metabolism, are presented. The incorporation of appropriate surrogate species and biomarkers of chronic toxicity into standard toxicity characterizations is proposed as a means of significantly refining the ecological hazard assessment process. PMID:9114278

  10. Chronic toxicity of ammonia to fathead minnows

    SciTech Connect

    Thurston, R.V.; Russo, R.C.; Meyn, E.L.; Zajdel, R.K.; Smith, C.E.

    1986-03-01

    Chronic effects of ammonia on the fathead minnow Pimephales promelas were studied in the laboratory in two flow-through tests, each test lasting approximately 1 year. Fish were exposed to five test concentrations over the range 0.07-0.96 mg/L un-ionized ammonia (NH/sub 3/); the mean pH of the test water was 8.0, and the mean temperature was 24.2/sup 0/C. The tests started with 3- to 5-d-old larvae that were reared to sexual maturity; progeny of these fish (F/sub 1/) were reared until they were 60 d old. The 5% probability level was chosen to indicate significance. No effects were observed on growth or survival of parental fish at 0.44 mg/L NH/sub 3/, or on egg production or viability at 0.37 mg/L, but effects on all of these were observed at 0.91 mg/L. Growth and survival of F/sub 1/ larvae were not affected at 0.36 mg/L NH/sub 3/, which was the highest concentration at which these were tested. Egg hatching success was not affected at 0.19 mg/L NH/sub 3/, but was at 0.37 mg/L. Brain lesions were common in parental fish at all stages of development at exposure concentrations of 0.21 mg/L NH/sub 3/ and higher, but not at 0.11 mg/L; no other histopathologic effects were observed at any of the test concentrations. The chronic-effects threshold concentration, based on survival, growth, and reproductive success, is estimated to be 0.27 mg/L NH/sub 3/ for the conditions of these tests. Based on histological damage, however, this concentration is estimated to be 0.15 mg/L NH/sub 3/.

  11. A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response

    SciTech Connect

    Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.; Salim, Elsayed I.; Kinoshita, Anna; Yoshida, Kaoru; Endo, Ginji; Fukushima, Shoji . E-mail: fukuchan@med.osaka-cu.ac.jp

    2006-02-01

    Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects of MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.

  12. Accuracy of Chronic Aquatic Toxicity Estimates Determined from Acute Toxicity Data and Two Time–Response Models.

    EPA Science Inventory

    Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of...

  13. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    SciTech Connect

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  14. Assessment of chronic inhalation non-cancer toxicity for diethylamine.

    PubMed

    Grant, Roberta L; Taiwo, Samuel O; McCant, Darrell

    2015-01-01

    A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose-response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m(3)). PMID:26671196

  15. Assessment of chronic inhalation non-cancer toxicity for diethylamine

    PubMed Central

    Grant, Roberta L.; Taiwo, Samuel O.; McCant, Darrell

    2015-01-01

    Abstract A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose–response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m3). PMID:26671196

  16. Meta-analysis of aquatic chronic chemical toxicity data

    EPA Science Inventory

    Chronic toxicity data from the open literature and from tests submitted for pesticide registration were extracted and assembled into a database, AquaChronTox, with a flexible search interface. Data were captured at a treatment and, when available, replicate level to support conc...

  17. Influence of chloride on the chronic toxicity of sodium nitrate to Ceriodaphnia dubia and Hyalella azteca.

    PubMed

    Soucek, David J; Dickinson, Amy

    2016-09-01

    While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia. We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable. PMID:27386878

  18. [Preclinical study of noopept toxicity].

    PubMed

    Kovalenko, L P; Smol'nikova, N M; Alekseeva, S V; Nemova, E P; Sorokina, A V; Miramedova, M G; Kurapova, S P; Sidorina, E I; Kulakova, A V; Daugel'-Dauge, N O

    2002-01-01

    Within the framework of a preclinical investigation, the new nootrope drug noopept (N-phenyl-acetyl-L-propyl-glycine ethylate) was tested for chronic toxicity upon peroral administration in a dose of 10 or 100 mg/kg over 6 months in both male and female rabbits. The results of observations showed that noopept administered in this dose range induced no irreversible pathologic changes in the organs and systems studied and exhibited no allergenic, immunotoxic, and mutagen activity. The drug affected neither the generative function nor the antenatal or postnatal progeny development. Noopept produced a dose-dependent suppression of inflammation reaction to concanavalin A and stimulated the cellular and humoral immune response in mice. PMID:12025790

  19. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  20. Passive Dosing in Chronic Toxicity Tests with the Nematode Caenorhabditis elegans.

    PubMed

    Fischer, Fabian; Böhm, Leonard; Höss, Sebastian; Möhlenkamp, Christel; Claus, Evelyn; Düring, Rolf-Alexander; Schäfer, Sabine

    2016-09-01

    In chronic toxicity tests with Caenorhabditis elegans, it is necessary to feed the nematode with bacteria, which reduces the freely dissolved concentration (Cfree) of hydrophobic organic chemicals (HOCs), leading to poorly defined exposure with conventional dosing procedures. We examined the efficacy of passive dosing of polycyclic aromatic hydrocarbons (PAHs) using silicone O-rings to control exposure during C. elegans toxicity testing and compared the results to those obtained with solvent spiking. Solid-phase microextraction and liquid-liquid extraction were used to measure Cfree and the chemicals taken up via ingestion. During toxicity testing, Cfree decreased by up to 89% after solvent spiking but remained constant with passive dosing. This led to a higher apparent toxicity on C. elegans exposed by passive dosing than by solvent spiking. With increasing bacterial cell densities, Cfree of solvent-spiked PAHs decreased while being maintained constant with passive dosing. This resulted in lower apparent toxicity under solvent spiking but an increased apparent toxicity with passive dosing, probably as a result of the higher chemical uptake rate via food (CUfood). Our results demonstrate the utility of passive dosing to control Cfree in routine chronic toxicity testing of HOCs. Moreover, both chemical uptake from water or via food ingestion can be controlled, thus enabling the discrimination of different uptake routes in chronic toxicity studies. PMID:27494096

  1. Results of chronic dietary toxicity studies of high viscosity (P70H and P100H) white mineral oils in Fischer 344 rats.

    PubMed

    Trimmer, Gary W; Freeman, James J; Priston, R A J; Urbanus, Jan

    2004-01-01

    Two-year dietary studies were conducted to determine the chronic toxicity and its reversibility, and the carcinogenicity of P70(H) and P100(H) white mineral oils in Fischer-344 rats (F-344). The studies were identical in design and followed the Organization for Economic Cooperation and Development, Guidelines for Testing Chemicals, Guideline 453, 1981. Additional endpoints evaluated were: (1) extent of mineral hydrocarbon deposition in liver, kidneys, mesenteric lymph nodes, and spleen of female rats at 3, 6, 12, 18 and 24 months, and (2) reversibility of effects following cessation of exposure. Dietary concentration were 60, 120, 240, and 1,200 mg/kg/day, adjusted periodically to account for bodyweight changes. Study results were consistent with preceding subchronic studies. No treatment-related mortality, neoplastic lesions, or changes in clinical health, hematology, serum chemistry, or urine chemistry were evident in any group administered either white oil. Statistically significant higher food consumption was noted in the 1,200 mg/kg group males and females exposed to either white oil and statistically significant higher body weights were noted in the 1,200-mg/kg males during the latter portion of the P100(H) study. Higher mesenteric lymph node weights were accompanied by increased severity of infiltrating histiocytes. This occurred to a greater extent with the P70(H) than the P100(H) oil. No other histopathology of significance was observed. Mineral hydrocarbons were detected in the liver following exposure to either oil. Maximal concentrations of mineral hydrocarbons in the liver were similar with both oils but occurred more rapidly with the P70(H) oil. Liver mineral hydrocarbon content returned to near-background levels during the reversibility phase. In conclusion, lifetime exposer of F344 rats to P70(H) and P100(H) white oils resulted in only minimal findings and with no consequence to clinical health. Thus, under the conditions of these studies, the No

  2. Comparison of whole effluent chronic toxicity to receiving stream ecological conditions

    SciTech Connect

    Smith, G.J.; McIntyre, D.O.; Clement, W.H.; Green, S.

    1995-12-31

    The relationship between whole effluent toxicity (WET) and effects to receiving stream communities was investigated by comparing Ceriodaphnia dubia chronic toxicity data to instream chemical and biological data collected from a third-order and fifth order stream. Effluent from a POTW was intermittently toxic to C. dubia (an average of 1.5 to 2.5 TU{sub c}s), and a Toxicity Identification Evaluation (TIE) conducted on the effluent determined the toxicity to C. dubia was primarily caused by nickel and zinc. MINTEQA2 equilibrium metal speciation modelling analysis of TIE data also found that nickel and zinc were the metal species/complexes most highly correlated (r values ranged from 0.5 to 0.7) with the C. dubia chronic toxicity levels. The one year study consisted of monthly final effluent chronic biomonitoring conducted in conjunction with monthly chemical measurements (general water quality measurements and selected heavy metals) and quarterly biological measurements (ambient chronic C. dubia toxicity and assemblages of macroinvertebrates and fish). The third-order stream showed an increase in the instream concentrations of chloride, total phosphorus, specific conductivity, nitrite-N, nickel and zinc downstream of the effluent discharge, but the downstream macroinvertebrate community was more abundant and diverse relative to macroinvertebrate community upstream of the effluent. The concentrations of these same parameters were not significantly increased in the fifth-order stream, and there was likewise no observed impact to the fifth-order stream communities. Thus, based on the study data, the intermittently chronically toxic POTW effluent did not adversely impact the biological communities of the downstream third-order and fifth-order receiving streams.

  3. DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

    EPA Science Inventory

    Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

  4. Chronic toxicity of some new insecticides to bobwhite quail

    USGS Publications Warehouse

    Linduska, J.P.; Springer, P.F.

    1951-01-01

    Presents and discusses results of toxicity studies on northern bobwhite (Colinus virginianus). Compounds tested were chlordane, toxaphene, DDT, benzene hexachioride, methoxychior, TDE (Rhothane}, and parathion.

  5. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    2013-10-01

    Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

  6. LITHIUM TOXICITY - A DESCRIPTIVE STUDY

    PubMed Central

    Kumar, Ratanendra; Deb, Jayant Kumar; Sinha, Baxi Neeraj Prasad; Sinha, Vinod Kumar

    2001-01-01

    Lithium is the treatment for acute mania and bipolar disorders. Ever since its introduction in the psychiatric arsenal, case reports of toxicity have been appearing in the literature at regular intervals. This study was thus carried out to study the presentation and associated features of lithium toxicity. In this retrospective study, case record files of all patients suspected to have developed lithium toxicity during a five year period were retrieved. It was found that toxicity presented most commonly with cerebellar symptoms and appeared at lower serum levels. Lithium could be restarted albeit at a lower dose and with a gradual titration in a number of cases. PMID:21407839

  7. Acute and chronic toxicity of lead in water and diet to the amphipod Hyalella azteca

    USGS Publications Warehouse

    Besser, J.M.; Brumbaugh, W.G.; Brunson, E.L.; Ingersoll, C.G.

    2005-01-01

    We evaluated the influence of waterborne and dietary lead (Pb) exposure on the acute and chronic toxicity of Pb to the amphipod Hyalella azteca. Test solutions were generated by a modified diluter with an extended (24-h) equilibration period. Acute (96-h) toxicity of Pb varied with water hardness in the range of 71 to 275 mg/L as CaCO3, despite similar dissolved Pb concentrations. Acute toxicity was greatest in soft test water, with less than 50% survival at the lowest dissolved Pb concentration (151 ??g/L). Survival also was significantly reduced in medium-hardness water but not in hard test water. In chronic (42-d) studies, amphipods were exposed to waterborne Pb and fed either a control diet or a diet equilibrated with waterborne Pb levels. For animals fed the control diet, the median lethal concentration (LC50) for Pb was 24 ??g/L (as dissolved Pb), and significant reductions in survival occurred at 16 ??g/L. Exposure to Pb-treated diets significantly increased toxicity across a wide range of dissolved Pb concentrations, with a LC50 of 16 ??g/L and significant reductions in growth and reproduction at 3.5 ??g/L. Significant effects on growth and reproduction occurred at dissolved Pb concentrations close to the current U.S. chronic water-quality criterion. Our results suggest that both aqueous- and dietary-exposure pathways contribute significantly to chronic Pb exposure and toxic effects in aquatic biota. ?? 2005 SETAC.

  8. Aminomethylphosphonic acid has low chronic toxicity to Daphnia magna and Pimephales promelas.

    PubMed

    Levine, Steven L; von Mérey, Georg; Minderhout, Tui; Manson, Philip; Sutton, Peter

    2015-06-01

    Aminomethylphosphonic acid (AMPA) is the simplest member of a class of compounds known as aminomethylenephosphonates and the only environmental metabolite measured in significant amounts during the degradation of the herbicide glyphosate in soil. However, there are additional sources of AMPA in the environment, originating from organic phosphonates which are used in water treatment to inhibit scale formation and corrosion. Like glyphosate, AMPA has low acute toxicity to aquatic animals, and the no-observed-adverse effect concentration (NOAEC) obtained from a fish full-life cycle study for glyphosate was determined to be 26 mg/L. However, the chronic toxicity of AMPA to aquatic animals has not been evaluated before. The purpose of the present study was to assess the potential for chronic toxicity of AMPA to fathead minnow (Pimephales promelas) and Daphnia magna. Chronic toxicity to P. promelas was evaluated in a fish early-life stage study. The primary endpoints were larval survival, growth, and development. The NOAEC for P. promelas was determined to be 12 mg/L, the highest concentration tested. The chronic toxicity to D. magna was evaluated in a Daphnia reproduction test. The primary endpoints were survival, growth, and reproduction. The no-observed-effect concentration for D. magna was determined to be 15 mg/L. Conservatively predicted environmental surface water concentrations for AMPA from typical foliar agricultural application rates and values from surface water monitoring programs are 100 to 1000 times less than the NOAEC values from both studies. Consequently, there is a large and highly protective margin of safety between realistic environmental exposures to AMPA and chronic toxicity to aquatic vertebrates and invertebrates. PMID:25690938

  9. Development of a short-term chronic toxicity test with a tropical mysid.

    PubMed

    Figuerêdo, Lívia Pitombeira de; Nilin, Jeamylle; Silva, Allyson Queiroz da; Loureiro, Susana; Costa-Lotufo, Letícia Veras

    2016-05-15

    There is an increasing need to develop reliable methodologies for chronic toxicity testing using tropical species. The present work aimed at developing a suitable short-term chronic toxicity test with Mysidopsis juniae using zinc (Zn) and nickel (Ni) as model chemicals and growth (length and dry weight), survival, and egg production (number of females with eggs) as endpoints after seven days of exposure. Survival and growth of newborn M. juniae were affected by chronic exposure to zinc, while nickel affected only survival. For zinc, dry weight was the most sensitive endpoint with significant effects even at the lowest tested concentration (75μgZn·L(-1)), whereas for nickel, survival was the most sensitive parameter (LC20 of 26μgNi·L(-1)). Egg production was not affected. M. juniae short-term chronic testing is a sensitive approach to evaluating metal toxicity; further studies are necessary to assess chronic toxicity for others contaminants in the proposed assay. PMID:27001717

  10. Chronic toxicity of dietary copper to Daphnia magna.

    PubMed

    De Schamphelaere, K A C; Forrez, I; Dierckens, K; Sorgeloos, P; Janssen, C R

    2007-03-30

    There is a growing concern that dietborne metal toxicity might be important in aquatic ecosystems. However, the science behind this matter is insufficiently developed to explicitly and accurately account for this in metal regulation or risk assessment. We investigated the effects of a chronic exposure of Daphnia magna to an elevated level of Cu (3000 microg Cu/g dry wt) in their diet (the green alga Pseudokirchneriella subcapitata). Compared to daphnids fed with P. subcapitata containing a background of 10.6 microg Cu/g dry wt, daphnids fed for 21 days with this Cu-contaminated food accumulated a total copper body burden of 325 microg Cu/g dry wt, which is about 30-fold higher than the control body burden of 12.1 microg/g dry wt. The exposed daphnids experienced a 38% reduction of growth (measured as final dry body weight), a 50% reduction of reproduction (total number of juveniles produced per daphnid), and only produced three broods versus four broods by the control daphnids. Unlike most other studies, we were able to demonstrate that these effects were most likely not due to a reduced nutritional quality of the food, based on C:P ratios and fatty acid content and composition of the Cu-contaminated algae. Life-history analysis showed that time to first brood was not affected by dietary Cu, while the second and third broods were significantly delayed by 0.7 and 1.5 days, respectively. On the other hand, brood sizes of all three broods were significantly lower in Cu exposed daphnids, i.e. by 32-55%. The variety of effects observed suggest the possible, and perhaps simultaneous, involvement of several toxicity mechanisms such as increased metabolic cost, reduced energy acquisition (potentially via inhibition of digestive enzyme activity), targeted inhibition of reproduction (potentially via inhibition of vitellogenesis), and/or direct inhibition of molting. Further research is needed to differentiate between these postulated mechanisms of dietary Cu toxicity and to

  11. [Chronic toxicity of tobacco smoke on the visual system].

    PubMed

    Oku, H; Fukushima, K; Sako, H; Namba, T; Wakakura, M

    1989-05-01

    The chronic toxicity of tobacco smoke on the rats visual system was studied. Six male Wistar rats had been subjected to five hour's daily passive smoking of 15 cigarettes for 52 weeks, in an attempt to produce tobacco amblyopia. Elongation of the peak latency time of N1 and P1 waves in the visual evoked potential (VEP) was recognized. Histopathologically, some degree of glial proliferation and pyknosis was observed in the optic nerves of all treated rats, and massive disappearance of nerve fibers was seen in one severely affected case. Electron microscopic examination proved that unmyelinated nerve fibers increased in number and the myelin sheath was thinner than that of the untreated control rats, while axons were relatively well preserved. The distribution in the magnitude of the axon diameter histogram was shifted towards a smaller diameter than that of the control rats. Electroretinography (ERG) did not show any significant changes of the latency and the amplitude of both a- and b- waves, and no histopathological changes were seen in the sensory retina. Neither functional nor histological changes were seen in the sciatic nerves. These results indicated that the optic nerve is thought to be more vulnerable to tobacco smoke than the peripheral nerves and we consider that a primary change of the nerve is demyelination at the retrobulbar portion of the optic nerve. PMID:2801365

  12. Chronic toxicity of silver nitrate to Ceriodaphnia dubia and Daphnia magna, and potential mitigating factors.

    PubMed

    Naddy, Rami B; Gorsuch, Joseph W; Rehner, Anita B; McNerney, Gina R; Bell, Russell A; Kramer, James R

    2007-08-15

    We investigated the chronic toxicity of Ag, as silver nitrate, using two freshwater aquatic cladoceran species, Ceriodaphnia dubia and Daphnia magna, to generate data for the development of a chronic ambient water quality criterion for Ag. Preliminary studies with C. dubia showed variable results which were related to the equilibration time between food and silver. Follow-up testing was conducted using a 3h equilibration time, which stabilized dissolved Ag concentrations and the toxicity of Ag(+). Results with C. dubia conducted individually (1 per cup, n=10) and in mass (30 per chamber, n=2) gave similar results once similar standardized equilibration times were used. The maximum acceptable toxicant concentration (MATC) of Ag to C. dubia and D. magna was 9.61 and 3.00microg dissolved Ag/L, respectively. The chronic toxicity of Ag(+) to C. dubia was also evaluated in the presence of: (1) dissolved organic carbon (DOC) and (2) sulfide. The addition of DOC (0.4mg/L) resulted in a approximately 50% decrease in toxicity while the addition of sulfide (75.4nM) deceased toxicity by 42%. Whole-body Ag concentration in D. magna was positively correlated with increased levels of Ag exposure, however; we observed a non-statistical decrease in whole-body Na levels, an estimator of sodium homeostasis. PMID:17658626

  13. MICROBIAL TOXICITY STUDIES

    EPA Science Inventory

    The chapter cites examples of the common methods used to determine the toxicity of chemicals to bacteria. It covers only the most common methods, particularly those that are easy to perform. Numerous literature citations have been included to help illustrate how a method is used ...

  14. Results of chronic toxicity tests conducted on selected A-area outfalls, June-August 1996

    SciTech Connect

    Specht, W.L.

    1997-07-01

    In anticipation of possible toxicity testing requirements in the SRS`s new (1996) NPDES permit, toxicity tests were performed at selected A-Area NPDES outfalls in order to determine if the outfalls were toxic. Chronic definitive toxicity tests were conducted on Ceriodaphnia dubia using water collected from nine locations during the summer of 1996. Six of the nine locations were toxic.

  15. The chronic aquatic toxicity of a microbicide dibromonitrilopropionamide.

    PubMed

    Chen, Fang

    2012-03-01

    The chronic aquatic toxicities of a microbicide dibromonitrilopropionamide (DBNPA) in Daphnia magna and rainbow trout were evaluated. DBNPA can significantly affect the reproduction and survival of D. magna. The lowest observed effective concentration (LOEC) and the no observed effective concentration (NOEC) of DBNPA to D. magna were 0.053 and 0.072 mg L(-1), respectively, and the intrinsic rate of natural increase (r) was significantly decreased (p < 0.05) at a concentration of 0.01 mg L(-1). Meanwhile, DBNPA affected the growth of juvenile rainbow trout at a concentration of 0.01875 mg L(-1) after 28-day exposure. The results showed that DBNPA has chronic deleterious effects on aquatic organisms. PMID:21937531

  16. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  17. Behavior and chronic toxicity of two differently stabilized silver nanoparticles to Daphnia magna.

    PubMed

    Sakka, Yvonne; Skjolding, Lars Michael; Mackevica, Aiga; Filser, Juliane; Baun, Anders

    2016-08-01

    While differences in silver nanoparticle (AgNP) colloidal stability, surface potential, or acute aquatic toxicity for differently stabilized AgNP have often been reported, these have rarely been studied in long-term ecotoxicity tests. In the current study, we investigated the chronic toxicity of AgNP to Daphnia magna over a 21-day period with two different stabilizers (citrate and detergent), representative for charge and sterical stabilizers, respectively. This was coupled with a series of short-term experiments, such as mass balance and uptake/depuration testing, to investigate the behavior of both types of AgNP during a typical media exchange period in the D. magna test for chronic toxicity. As expected, the sterically stabilized AgNP was more stable in the test medium, also in the presence of food; however, a higher uptake of silver after 24h exposure of the charge stabilized AgNP was found compared to the detergent-stabilized AgNP (0.046±0.006μgAgμgDW(-1) and 0.023±0.005μgAgμgDW(-1), respectively). In accordance with this, the higher reproductive effects and mortality were found for the charge-stabilized than for the sterically-stabilized silver nanoparticles in 21-d tests for chronic toxicity. LOEC was 19.2μgAgL(-1) for both endpoints for citrate-coated AgNP and >27.5μgAgL(-1) (highest tested concentration for detergent-stabilized AgNP). This indicates a link between uptake and toxicity. The inclusion of additional short-term experiments on uptake and depuration is recommended when longer-term chronic experiments with nanoparticles are conducted. PMID:27449283

  18. Evaluation of Acute and Chronic Toxicities of the Water Extract from Ziziphus attopensis Pierre

    PubMed Central

    Sireeratawong, Seewaboon; Vannasiri, Supaporn; Nanna, Urarat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    We studied an acute and chronic oral toxicity of the extract from Ziziphus attopensis (ZA) in male and female SD rats according to the OECD guidelines. After a single oral administration of ZA 5 g/kg body weight, measurement of the body and organs, necropsy, and health monitoring were performed. The body and organ weights and behavior were not changed relative to the control rats indicating that ZA does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with ZA at the doses of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes, hematological and biochemical parameters, organ weights, gross finding, and histopathology examination were monitored during the experimental period. The results did not show any differences from the control groups. Analyses of these results with the information of signs, behavior, and health monitoring can lead to a conclusion that the long-term oral administration of ZA for 180 days does not cause chronic toxicity. PMID:22474597

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

    PubMed

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

    2013-01-01

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

  20. Toxic stress, inflammation and symptomatology of chronic complications in diabetes

    PubMed Central

    Downs, Charles A; Faulkner, Melissa Spezia

    2015-01-01

    Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035. The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009. The effects of toxic stress, the culmination of biological and environmental interactions, on the development of diabetes complications is gaining attention. Stress impacts the hypothalamus-pituitary-adrenal axis and contributes to inflammation, a key biological contributor to the pathogenesis of diabetes and its associated complications. This review provides an overview of common diabetic complications such as neuropathy, cognitive decline, depression, nephropathy and cardiovascular disease. The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes, associated symptomatology and importance of early identification of symptoms of depression, fatigue, exercise intolerance and pain. PMID:25987953

  1. Assessment of sub-chronic, hematological and histopathological toxicities of a herbal combination.

    PubMed

    Ahmed, Shadab; Khan, Rafeeq Alam; Feroz, Zeeshan

    2015-11-01

    The herbal combination under study consists of Withania somnifera, Tribulus terrestris, Mucuna pruriens and Argyria speciosa. Present study is mainly designed to investigate the gross physical, sub-chronic, hematological and histopathological effects of the combination widely used for its stimulating, revitalizing and fertility boosting effects in Pakistan. Sub-chronic, hematological and histopathological outcomes of herbal combination were assessed on 27 albino rabbits weighing from 1000 gm-1500 gm after giving herbal combination for 60 days in two doses 27 and 81 mg/kg against control. No significant toxicity was revealed during the entire period of study, however some biochemical changes were observed in kidney and liver but these changes did not coincide with histopathological findings. There was no mortality and evidence of systemic toxicity including hematological toxicity following 60 days administration of herbal combination. Results of present study suggest that further studies are required on large number of animals before reaching to a definite conclusion, more over clinical studies should also be conducted to confirm the possible toxic effects of the herbal combination. PMID:26639483

  2. Optimizing the performance of the amphipod, Hyalella azteca, in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

    EPA Science Inventory

    The freshwater amphipod, Hyalella azteca, is a common organism used for sediment toxicity testing. Standard methods for 10-d and 42-d sediment toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. While Hyalella azteca methods exist for sediment tox...

  3. Chronic toxicity of tire and road wear particles to water- and sediment-dwelling organisms.

    PubMed

    Panko, Julie M; Kreider, Marisa L; McAtee, Britt L; Marwood, Christopher

    2013-01-01

    Tire and road wear particles (TRWP) consist of a complex mixture of rubber, and pavement released from tires during use on road surfaces. Subsequent transport of the TRWP into freshwater sediments has raised some concern about the potential adverse effects on aquatic organisms. Previous studies have shown some potential for toxicity for tread particles, however, toxicity studies of TRWP collected from a road simulator system revealed no acute toxicity to green algae, daphnids, or fathead minnows at concentrations up to 10,000 mg/kg under conditions representative of receiving water bodies. In this study, the chronic toxicity of TRWP was evaluated in four aquatic species. Test animals were exposed to whole sediment spiked with TRWP at concentrations up to 10,000 mg/kg sediment or elutriates from spiked sediment. Exposure to TRWP spiked sediment caused mild growth inhibition in Chironomus dilutus but had no adverse effect on growth or reproduction in Hyalella azteca. Exposure to TRWP elutriates resulted in slightly diminished survival in larval Pimephales promelas but had no adverse effect on growth or reproduction in Ceriodaphnia dubia. No other endpoints in these species were affected. These results, together with previous studies demonstrating no acute toxicity of TRWP, indicate that under typical exposure conditions TRWP in sediments pose a low risk of toxicity to aquatic organisms. PMID:23001428

  4. Chronic toxic encephalopathy in a painter exposed to mixed solvents.

    PubMed Central

    Feldman, R G; Ratner, M H; Ptak, T

    1999-01-01

    This paper describes symptoms and findings in a 57-year-old painter who had been exposed to various organic solvents for over 30 years. He began to work as a painter at 16 years of age, frequently working in poorly ventilated areas; he used solvents to remove paint from the skin of his arms and hands at the end of each work shift. The patient and his family noticed impaired short-term memory function and changes in affect in his early forties, which progressed until after he stopped working and was thus no longer exposed to paints and solvents. After the patient's exposures had ended, serial neuropsychological testing revealed persistent cognitive deficits without evidence of further progression, and improvement in some domains. Magnetic resonance imaging revealed global and symmetrical volume loss, involving more white than gray matter. The findings in this patient are consistent with chronic toxic encephalopathy and are differentiated from other dementing processes such as Alzheimer's disease, multi-infarct (vascular) dementia, and alcoholic dementia. Previous descriptions in the literature of persistent neurobehavioral effects associated with chronic exposure to organic solvents corroborate the findings in this case. Images Figure 2 PMID:10210698

  5. Chronic toxicity of copper and ammonia to juvenile freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Greer, I.E.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; Brumbaugh, W.G.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

    2007-01-01

    The objectives of the present study were to develop methods for conducting chronic toxicity tests with juvenile mussels under flow-through conditions and to determine the chronic toxicity of copper and ammonia to juvenile mussels using these methods. In two feeding tests, two-month-old fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris) were fed various live algae or nonviable algal mixture for 28 d. The algal mixture was the best food resulting in high survival (???90%) and growth. Multiple copper and ammonia toxicity tests were conducted for 28 d starting with two-month-old mussels. Six toxicity tests using the algal mixture were successfully completed with a control survival of 88 to 100%. Among copper tests with rainbow mussel, fatmucket, and oyster mussel (Epioblasma capsaeformis), chronic value ([ChV], geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) ranged from 8.5 to 9.8 ??g Cu/L for survival and from 4.6 to 8.5 ??g Cu/L for growth. Among ammonia tests with rainbow mussel, fatmucket, and wavy-rayed lampmussel (L. fasciola), the ChV ranged from 0.37 to 1.2 mg total ammonia N/L for survival and from 0.37 to 0.67 mg N/L for growth. These ChVs were below the U.S. Environmental Protection Agency 1996 chronic water quality criterion (WQC) for copper (15 ??g/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20??C). Results indicate that toxicity tests with two-month-old mussels can be conducted for 28 d with >80% control survival; growth was frequently a more sensitive endpoint compared to survival; and the 1996 chronic WQC for copper and the 1999 chronic WQC for total ammonia might not be adequately protective of the mussel species tested. However, a recently revised 2007 chronic WQC for copper based on the biotic ligand model may be more protective in the water tested. ?? 2007 SETAC.

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

    PubMed Central

    Chavan, Swapnil; Friedman, Ran; Nicholls, Ian A.

    2015-01-01

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. PMID:26006240

  7. Chronic toxicity evaluation of simulated DWPF effluent to Ceriodaphnia dubia. Revision 1

    SciTech Connect

    Not Available

    1990-04-01

    A 7-Day Full Series Chronic Toxicity test was conducted April 13--20, 1990, for the Savannah River Site to assess the chronic toxicity of Simulated defense waste processing facility (DWPF) effluent to Ceriodaphnia dubia. The simulated effluented consisted of Sodium Nitrate, Sodium Oxalate, Sodium Formate, and Corros. Inib.

  8. Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity.

    PubMed

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W; Li, Song; Xie, Wen

    2015-04-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  9. Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity

    PubMed Central

    Cheng, Qiuqiong; Inaba, Yuka; Lu, Peipei; Xu, Meishu; He, Jinhan; Zhao, Yueshui; Guo, Grace L.; Kuruba, Ramalinga; de la Vega, Rona; Evans, Rhobert W.; Li, Song

    2015-01-01

    The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage. PMID:25719402

  10. Chronic toxicity of nickel-spiked freshwater sediments: variation in toxicity among eight invertebrate taxa and eight sediments.

    PubMed

    Besser, John M; Brumbaugh, William G; Ingersoll, Christopher G; Ivey, Chris D; Kunz, James L; Kemble, Nile E; Schlekat, Christian E; Garman, Emily Rogevich

    2013-11-01

    This study evaluated the chronic toxicity of Ni-spiked freshwater sediments to benthic invertebrates. A 2-step spiking procedure (spiking and sediment dilution) and a 2-stage equilibration period (10 wk anaerobic and 1 wk aerobic) were used to spike 8 freshwater sediments with wide ranges of acid-volatile sulfide (AVS; 0.94-38 µmol/g) and total organic carbon (TOC; 0.42-10%). Chronic sediment toxicity tests were conducted with 8 invertebrates (Hyalella azteca, Gammarus pseudolimnaeus, Chironomus riparius, Chironomus dilutus, Hexagenia sp., Lumbriculus variegatus, Tubifex tubifex, and Lampsilis siliquoidea) in 2 spiked sediments. Nickel toxicity thresholds estimated from species-sensitivity distributions were 97 µg/g and 752 µg/g (total recoverable Ni; dry wt basis) for sediments with low and high concentrations of AVS and TOC, respectively. Sensitive species were tested with 6 additional sediments. The 20% effect concentrations (EC20s) for Hyalella and Gammarus, but not Hexagenia, were consistent with US Environmental Protection Agency benchmarks based on Ni in porewater and in simultaneously extracted metals (SEM) normalized to AVS and TOC. For Hexagenia, sediment EC20s increased at less than an equimolar basis with increased AVS, and toxicity occurred in several sediments with Ni concentrations in SEM less than AVS. The authors hypothesize that circulation of oxygenated water by Hexagenia led to oxidation of AVS in burrows, creating microenvironments with high Ni exposure. Despite these unexpected results, a strong relationship between Hexagenia EC20s and AVS could provide a basis for conservative site-specific sediment quality guidelines for Ni. PMID:23657897

  11. Chronic toxicity of 14 phthalate esters to Daphnia magna and rainbow trout (Oncorhynchus mykiss)

    SciTech Connect

    Rhodes, J.E.; Adams, W.J.; Biddinger, G.R.; Robillard, K.A.; Gorsuch, J.W.

    1995-11-01

    Chronic toxicity studies were performed with commercial phthalate esters and Daphnia magna (14 phthalates) and rainbow trout (Oncorhynchus mykiss) (six phthalates). For the lower-molecular-weight phthalate esters--dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), and butylbenzyl phthalate (BBP)--the results of the studies indicated a general trend in which toxicity for both species increased as water solubility decreased. The geometric mean maximum acceptable toxicant concentration(GM-MATC) for D. magna ranged from 0.63 to 34.8 mg/L. For the higher-molecular-weight phthalate esters--dihexyl phthalate (DHP), butyl 2-ethylhexyl phthalate (BOP), di-(n-hexyl, n-octyl, n-decyl) phthalate (610P), di-(2-ethylhexyl) phthalate (DEHP), diisooctyl phthalate (DIOP), diisononyl phthalate (DINP), di-(heptyl, nonyl, undecyl) phthalate (711P), diisodecyl phthalate (DIDP), diundecyl phthalate (DUP), and ditridecyl phthalate (DTDP)--the GM-MATC values ranged from 0.042 to 0.15 mg/L. Survival was equally sensitive and sometimes more sensitive than reproduction. The observed toxicity to daphnids with most of the higher-molecular-weight phthalate esters appeared to be due to surface entrapment or a mode of toxicity that is not due to exposure to dissolved aqueous-phase chemical. Early life-stage toxicity studies with rainbow trout indicated that survival (DMP) and growth (DBP) were affected at 24 and 0.19 mg/L, respectively. This pattern of observed toxicity with the lower-molecular-weight phthalate esters and not the higher-molecular-weight phthalate esters is consistent with previously reported acute toxicity studies for several aquatic species.

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

    PubMed

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

    2014-09-01

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

  13. Temperature preference as an indicator of the chronic toxicity of cupric ions to Mozambique Tilapia

    SciTech Connect

    Welch, T.J.; Stauffer, J.R. Jr.; Morgan, R.P. II )

    1989-11-01

    Evaluation of the effects of environmental contaminants on aquatic communities has focused primarily on acute bioassays. These bioassays provide rapid and reproducible concentration response curves based on death as an endpoint. In recent years, however, emphasis has shifted towards monitoring sublethal effects of toxicants. Temperature is an easily quantifiable parameter influencing both the behavior and survival of fishes. As poikilotherms, fish use behavioral responses to help regulate body temperature. Fish thermoregulatory behavior may be altered by various toxic substances. Some researchers found that a 24 hr exposure of sublethal concentrations of copper caused a significant decrease in preferred temperature of fathead minnows (Pimephales promelas), although the results were confounded due to variations in copper concentrations. In this study, the authors examined the feasibility of using acute temperature preference tests to assess the chronic toxicity of low concentrations of free cupric ions to Mozambique tilapia, Oreochromis mossambicus (Peters).

  14. A docking-based receptor library of antibiotics and its novel application in predicting chronic mixture toxicity for environmental risk assessment.

    PubMed

    Zou, Xiaoming; Zhou, Xianghong; Lin, Zhifen; Deng, Ziqing; Yin, Daqiang

    2013-06-01

    As organisms are typically exposed to chemical mixtures over long periods of time, chronic mixture toxicity is the best way to perform an environmental risk assessment (ERA). However, it is difficult to obtain the chronic mixture toxicity data due to the high expense and the complexity of the data acquisition method. Therefore, an approach was proposed in this study to predict chronic mixture toxicity. The acute (15 min exposure) and chronic (24 h exposure) toxicity of eight antibiotics and trimethoprim to Vibrio fischeri were determined in both single and binary mixtures. The results indicated that the risk quotients (RQs) of antibiotics should be based on the chronic mixture toxicity. To predict the chronic mixture toxicity, a docking-based receptor library of antibiotics and the receptor-library-based quantitative structure-activity relationship (QSAR) model were developed. Application of the developed QSAR model to the ERA of antibiotic mixtures demonstrated that there was a close affinity between RQs based on the observed chronic toxicity and the corresponding RQs based on the predicted data. The average coefficients of variations were 46.26 and 34.93 % and the determination coefficients (R (2)) were 0.999 and 0.998 for the low concentration group and the high concentration group, respectively. This result convinced us that the receptor library would be a promising tool for predicting the chronic mixture toxicity of antibiotics and that it can be further applied in ERA. PMID:23143826

  15. Acute and chronic toxicity of the benzoylurea pesticide, lufenuron, in the fish, Colossoma macropomum.

    PubMed

    Rafaela Leão Soares, Priscila; Lucas Corrêa de Andrade, André; Pinheiro Santos, Thamiris; Caroline Barros Lucas da Silva, Stephannie; Freitas da Silva, Jadson; Rodrigues Dos Santos, Amanda; Hugo Lima da Silva Souza, Elton; Magliano da Cunha, Franklin; Wanderley Teixeira, Valéria; Sales Cadena, Marilia Ribeiro; Bezerra de Sá, Fabrício; Bezerra de Carvalho Júnior, Luiz; Gonçalves Cadena, Pabyton

    2016-10-01

    Lufenuron is a benzoylurea insecticide that interfere in chitin synthesis in insects. Although lufenuron is widely used in agriculture and aquaculture, rare are studies described that relates to possible toxic effects in fish. This work aimed to evaluate acute and chronic toxic effects of benzoylurea pesticide (lufenuron) on biological parameters of Colossoma macropomum (Tambaqui). In the acute test, juveniles of Tambaqui were divided into control group and five experimental groups with exposure from 0.1 to 0.9 mg/L of lufenuron for 96 h. Animals were also submitted to chronic toxicity test for four months in concentrations of 0.1 and 0.3 mg/L of lufenuron, the concentration used in the treatment of ectoparasites in fish and 50% of LC50 96 h, respectively. The presence of hemorrhages was observed in eyes, fins and operculum of fish exposed to 0.7 and 0.9 mg/L of lufenuron. Histological analysis showed changes in the morphology of fish gills submitted to acute toxicity test, as lamellar aneurysm and blood congestion inside lamellae. Lufenuron promoted damage in fish retina as in ability to respond to stimuli in photoreceptors and in ON-bipolar cells in acute test. In chronic test, blood glucose analysis and morphometric parameters showed no significant differences (p > 0.05). In general, Tambaqui exhibited behaviors associated with stress when exposed to lufenuron. Thus, lufenuron showed several toxic effects in relation to biological parameters in Tambaqui. This concerns about the use and discard of lufenuron, and indicates the requirement of environmental actions to prevent potential contamination of aquatic biota. PMID:27448754

  16. Poorly controlled hypertension in a painter with chronic lead toxicity.

    PubMed Central

    Hu, H

    2001-01-01

    In 1984, a 56-year-old house painter developed intractable pain in his back and other joints. After several unrevealing medical work-ups, he was found to have a high blood lead level (122 microg/dL); he has a history of scraping and sanding lead paint without adequate protective measures. The patient was hospitalized and chelated with EDTA four times over the next 5 years; each time he felt better at the end of his treatment, but he returned to largely the same working conditions. He developed hypertension in April 1989, underwent a final chelation, and retired. He was subsequently followed on a regular basis with repeated measurement of lead levels in blood and bone (using a K-x-ray fluorescence instrument) as well as clinical parameters. In 1995 his blood pressure became difficult to control despite a sequential increase in his antihypertensive medication dosages and the addition of new medications. In 1997 he began calcium supplementation and a high-calcium diet; his blood pressure declined markedly, allowing him to taper off of two of his four antihypertensive medications. This case demonstrates an occupational activity (construction) that has now become the dominant source of lead exposure for U.S. adults, the importance of a good occupational history to suspecting and making a diagnosis, the possible outcomes of chronic lead toxicity, and the importance of preventing further exposure and using proper methods to treat acute toxicity. It also highlights a current major etiologic question, that is, whether and to what degree lead exposure contributes to the development of hypertension, and raises the issue of whether lead-induced hypertension constitutes a subset of hypertension that is especially amenable to therapy with dietary calcium. PMID:11171531

  17. Baltimore Air Toxics Study (BATS)

    SciTech Connect

    Sullivan, D.A.

    1996-12-31

    The Baltimore Air Toxics Study is one of the three urban air toxics initiatives funded by EPA to support the development of the national air toxics strategy. As part of this project, the Air Quality Integrated Management System (AIMS) is under development. AIMS is designed to bring together the key components of urban air quality management into an integrated system, including emissions assessment, air quality modeling, and air quality monitoring. Urban area source emissions are computed for a wide range of pollutants and source categories, and are joined with existing point source emissions data. Measured air quality data are used to evaluate the adequacy of the emissions data and model treatments as a function of season, meteorological parameters, and daytime/nighttime conditions. Based on tested model performance, AIMS provides the potential to improve the ability to predict air quality benefits of alternative control options for criteria and toxic air pollutants. This paper describes the methods used to develop AIMS, and provides examples from its application in the Baltimore metropolitan area. The use of AIMS in the future to enhance environmental management of major industrial facilities also will be addressed in the paper.

  18. How toxic is coal ash? A laboratory toxicity case study.

    PubMed

    Sherrard, Rick M; Carriker, Neil E; Greeley, Mark S

    2015-01-01

    Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. This brief communication describes a broad range of toxicity studies conducted for the Tennessee Valley Authority (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash. PMID:25348557

  19. How toxic is coal ash? A laboratory toxicity case study

    DOE PAGESBeta

    Sherrard, Rick M.; Carriker, Neil; Greeley, Jr., Mark Stephen

    2014-12-08

    Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. In this paper, we describe a broad range of toxicity studies conducted for the Tennessee Valley Authoritymore » (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash.« less

  20. How toxic is coal ash? A laboratory toxicity case study

    SciTech Connect

    Sherrard, Rick M.; Carriker, Neil; Greeley, Jr., Mark Stephen

    2014-12-08

    Under a consent agreement among the Environmental Protection Agency (EPA) and proponents both for and against stricter regulation, EPA is to issue a new coal ash disposal rule by the end of 2014. Laboratory toxicity investigations often yield conservative estimates of toxicity because many standard test species are more sensitive than resident species, thus could provide information useful to the rule-making. However, few laboratory studies of coal ash toxicity are available; most studies reported in the literature are based solely on field investigations. In this paper, we describe a broad range of toxicity studies conducted for the Tennessee Valley Authority (TVA) Kingston ash spill, results of which help provide additional perspective on the toxicity of coal ash.

  1. Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

    SciTech Connect

    Holland, J.M.

    2001-01-16

    Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

  2. Wheat bran intake can attenuate chronic cadmium toxicity in mice gut microbiota.

    PubMed

    Li, Yuhui; Liu, Kaiyong; Shen, Jie; Liu, Yehao

    2016-08-10

    Environmental exposure to pollutants such as heavy metals is responsible for various altered physiological functions that are detrimental to health. Cadmium (Cd) is one of the most representative toxic, non-essential elements that can contaminate food and water. This study evaluated the protective effects of wheat bran, a selected prebiotic with good Cd binding ability, against Cd toxicity in mice. Thirty mice were divided into control and therapeutic groups. The control group was fed a low dietary fiber diet with no Cd for 8 weeks. In the therapeutic group, 100 mg L(-1) Cd was administered along with a diet of 10% wheat bran. First, the binding ability of wheat bran for Cd was measured along with the protection of cell growth in vitro by wheat bran. Second, the effectiveness of wheat bran in preventing Cd from entering mice organs was evaluated. Finally, restoration of gut microbiota from alterations caused by Cd was investigated. The results showed that wheat bran could bind most of the Cd ions and restore the growth rate of cells in vitro. The wheat bran treatment group showed that the bran effectively prevented Cd from entering mice organs. In addition, the bacterial community structure was restored because the toxicity of Cd to gut microbiota was eliminated by the wheat bran. Our results suggest that wheat bran is more effective against chronic Cd toxicity than traditional treatments because of its special physiological functions, and it can be considered as a new dietary, therapeutic strategy against Cd toxicity. PMID:27425201

  3. Chronic fluoride exposure-induced testicular toxicity is associated with inflammatory response in mice.

    PubMed

    Wei, Ruifen; Luo, Guangying; Sun, Zilong; Wang, Shaolin; Wang, Jundong

    2016-06-01

    Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice. PMID:27031805

  4. Assessment of chronic toxicity from stormwater runoff in Lincoln Creek, Milwaukee, WI

    SciTech Connect

    Kleist, J.; Crunkilton, R.

    1995-12-31

    Stormwater runoff is believed to be responsible for a severely degraded biotic community in Lincoln Creek, a stream which drains portions of metropolitan Milwaukee. A previous study using Ceriodaphnia dubia and Pimephales promelas indicated little or no acute toxicity could be attributed to stormwater runoff. The purpose of this study was to assess the potential for chronic toxicity in the stream during periods of stormwater runoff. Reproduction and survival in Daphnia magna, and growth and survival in P. promelas were monitored to assess chronic effects. Seven consecutive 14 day tests were performed between June and September, 1994, in eighteen flow-through aquaria housed within a US Geological Survey gauging station located adjacent to Lincoln Creek. Mortality in D. magna consistently did not occur before day 4 of exposure, but averaged 64% at day 14. Reproduction in D. magna and growth in P. promelas in surviving individuals was not significantly reduced; all effects were manifested as mortality. Results of data analysis after 14 days of exposure contrast markedly with analysis made earlier in the same test. Statistical interpretation of the mortality data at typical endpoints of 48 hours for invertebrates and 96 hours for fish failed to identify adverse impacts of stormwater runoff the authors observed in longer exposures. Short-term toxicity tests appear insensitive to the detection of contaminant related effects. Long-term tests (greater than 7 days) were needed to identify adverse biological impacts that could in part explain the severely degraded biotic community of this urban stream.

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

    SciTech Connect

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

    2008-06-01

    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.

  6. Bioavailability-based chronic toxicity measurements of permethrin to Chironomus dilutus.

    PubMed

    Du, Juan; Pang, Junxiao; You, Jing

    2013-06-01

    Compared with acute toxicity, chronic exposures to low levels of contaminants are more environmentally relevant, but fewer data are available. In the present study, sediment toxicity of the pyrethoid permethrin to Chironomus dilutus was determined. The whole-life-cycle toxicity testing was conducted with the endpoints covering survival, growth, emergence, and reproduction. Permethrin caused 50% lethality in C. dilutus at 1.83 ± 1.13 µg/g organic carbon (OC) and 1.20 ± 0.55 µg/g OC after exposures of 20 d (before pupation) and 58 d (the end of the testing), respectively. The 5% and median effect concentrations (EC5 and EC50) represented the marginal and toxic levels of the sublethal effects, respectively, and effect data were all normalized to the controls before Probit analysis. The EC5s for growth, emergence, and reproduction were 0.034 ± 0.006 µg/g OC, 0.016 ± 0.008 µg/g OC, and 0.009 ± 0.008 µg/g OC, respectively; the respective EC50s were 1.09 ± 0.56 µg/g OC, 0.838 ± 0.077 µg/g OC, and 0.039 ± 0.105 µg/g OC. In addition, a 24-h Tenax extraction was employed to better assess permethrin bioavailability. Ultimately, response spectra with a series of endpoints were developed for permethrin using either OC-normalized bulk sediment concentrations or bioavailability-based Tenax extractable concentrations as the dose metric. The development of bioavailability-based chronic toxicity endpoints for sediment-associated permethrin would provide valuable benchmarks for evaluating ecological risk of this contaminant and contributing to improve sediment management policies. PMID:23424028

  7. Acutei and chronic toxicity of nickel to marine organisms: implications for water quality criteria.

    PubMed

    Hunt, John W; Anderson, Brian S; Phillips, Bryn M; Tjeerdema, Ron S; Puckett, H Max; Stephenson, Mark; Tucker, David W; Watson, Daniel

    2002-11-01

    Acute and chronic toxicity tests were conducted to determine the effects of nickel on three U.S. west coast marine species: a fish (the topsmelt, Atherinops affinis), a mollusk (the red abalone, Haliotis rufescens), and a crustacean (the mysid, Mysidopsis intii). The 96-h median lethal concentration (LC50) for topsmelt was 26,560 microg/L, and the chronic value for the most sensitive endpoint in a 40-d exposure was 4,270 microg/L. The median effective concentration (EC50) for 48-h abalone larval development was 145.5 microg/L, and the chronic value for juvenile growth in a 22-d exposure through larval metamorphosis was 26.43 microgAL. The mysid 96-h LC50 was 148.6 microg/L, and the chronic value for the most sensitive endpoint in a 28-d, whole life-cycle exposure was 22.09 microg/L. The abalone and mysid acute values were lower than other values available in the literature. Acute-to-chronic ratios for nickel toxicity to the three species were 6.220, 5.505, and 6.727, respectively, which were similar to the only other available saltwater value of 5.478 (for Americamysis [Mysidopsis] bahia) and significantly lower than the existing values of 35.58 and 29.86 for freshwater organisms. Incorporation of data from the present study into calculations for water quality criteria would lower the criterion maximum concentration and raise the criterion continuous concentration for nickel. PMID:12389922

  8. ESTIMATION OF AQUATIC SPECIES SENSITIVITY USING INTERSPECIES CORRELATION AND ACUTE TO CHRONIC TOXICITY MODELS

    EPA Science Inventory

    Abstract for presentation

    Estimation of aquatic species sensitivity using interspecies correlation and acute to chronic toxicity models

    Determining species sensitivity of aquatic organisms to contaminants is a critical component of criteria development and ecolog...

  9. ADVANTAGES OF USING REGRESSION ANALYSIS TO CALCULATE RESULTS OF CHRONIC TOXICITY TESTS

    EPA Science Inventory

    Although it is traditional to calculate results of chronic toxicity tests using hypothesis testing to detect statistically significant differences from the control, calculation of results using regression analysis offers several major advantages. Regression analysis can directly ...

  10. Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback and Produced Waters

    EPA Science Inventory

    As the use of hydraulic fracturing has increased, concerns have been raised about potential public health effects that may arise if hydraulic fracturing-related chemicals were to impact drinking water resources. This study presents an overview of the chronic oral toxicity values—...

  11. Chronic toxicity of arsenic to the Great Salt Lake brine shrimp, Artemia franciscana.

    PubMed

    Brix, Kevin V; Cardwell, Rick D; Adams, William J

    2003-02-01

    We determined the chronic toxicity of arsenic (sodium arsenate) to the Great Salt Lake brine shrimp, Artemia franciscana. Chronic toxicity was determined by measuring the adverse effects of arsenic on brine shrimp growth, survival, and reproduction under intermittent flow-through conditions. The study commenced with <24-h-old nauplii, continued through reproduction of the parental generation, and ended after 28 days of exposure. The concentrations tested were 4, 8, 15, 31, and 56mg/L dissolved arsenic. The test was conducted using water from the Great Salt Lake, Utah as the dilution water. Adult survival was the most sensitive biological endpoint, with growth and reproduction somewhat less sensitive than survival. The no observed effect concentration (NOEC) for survival was 8mg/L, and the lowest observed effect concentration (LOEC) was 15mg/L dissolved arsenic. The LOEC for growth and reproduction was greater than the highest concentration tested, 56mg/L. Based on survival, the final chronic value (geometric mean of the NOEC and LOEC) was 11mg/L dissolved arsenic. The F(1) generation appeared to acclimate to the prior arsenic exposure of the parental generation and was significantly less sensitive than the parental generation. For example, survival for the F(1) generation through day 12 was 100% in 56mg/L dissolved arsenic, compared to 26% for the parental generation. Growth of the F(1) generation was significantly less than that of the parental generation across all concentrations including the control, indicating a generational difference in brine shrimp growth rather than an arsenic effect. This study represents one of the few full life cycle toxicity tests conducted with brine shrimp. PMID:12550094

  12. DEVELOPMENT OF PROTOCOLS FOR CHRONIC TOXICITY TESTING OF PACIFIC MARINE SPECIES

    EPA Science Inventory

    Development of a year-round capability for conducting short-term toxicity tests for estimating chronic effect levels of toxic materials with a native Pacific coast fish and a native Pacific coast mysid shrimp was the goal of this project. n order to achieve acceptable sensitivity...

  13. The chronic toxicity of sodium bicarbonate, a major component of coal bed natural gas produced waters

    USGS Publications Warehouse

    Farag, Aida M.; Harper, David D.

    2014-01-01

    Sodium bicarbonate (NaHCO3) is the principal salt in coal bed natural gas produced water from the Powder River Structural Basin, Wyoming, USA, and concentrations of up to 3000 mg NaHCO3/L have been documented at some locations. No adequate studies have been performed to assess the chronic effects of NaHCO3 exposure. The present study was initiated to investigate the chronic toxicity and define sublethal effects at the individual organism level to explain the mechanisms of NaHCO3 toxicity. Three chronic experiments were completed with fathead minnows (Pimephales promelas), 1 with white suckers (Catostomus commersoni), 1 with Ceriodaphnia dubia, and 1 with a freshwater mussel, (Lampsilis siliquoidea). The data demonstrated that approximately 500 mg NaHCO3/L to 1000 mg NaHCO3/L affected all species of experimental aquatic animals in chronic exposure conditions. Freshwater mussels were the least sensitive to NaHCO3 exposure, with a 10-d inhibition concentration that affects 20% of the sample population (IC20) of 952 mg NaHCO3/L. The IC20 for C. dubia was the smallest, at 359 mg NaHCO3/L. A significant decrease in sodium–potassium adenosine triphosphatase (Na+/K+ ATPase) together with the lack of growth effects suggests that Na+/K+ ATPase activity was shut down before the onset of death. Several histological anomalies, including increased incidence of necrotic cells, suggested that fish were adversely affected as a result of exposure to >450 mg NaHCO3/L.

  14. The minipig as a new model for the evaluation of doxorubicin-induced chronic toxicity.

    PubMed

    Manno, Rosa Anna; Grassetti, Andrea; Oberto, Germano; Nyska, Abraham; Ramot, Yuval

    2016-08-01

    Doxorubicin can cause life-threatening toxic effects in several organs, with cardiotoxicity being the major concern. Although a large number of animal models have been utilized to study doxorubicin toxicity, several restrictions limit their use. Since the Göttingen minipig is an accepted species for non-clinical safety assessment and translation to man, we aimed at exploring its use as a non-rodent animal model for safety assessment and regulatory toxicity studies using doxorubicin. Three groups of three males and three females adult Göttingen minipigs received 1.5 mg kg(-1) , 3/2.3 mg kg(-1) or vehicle at intervals of 3 weeks for 7 cycles. Doxorubicin treatment resulted in a dose-related decrease in the erythrocytes, hemoglobin and hematocrit count, accompanied by leukopenia and thrombocytopenia. Bone marrow smears revealed dose-related hypocellularity. Urea and creatinine levels were elevated in treated animals, associated with proteinuria and hematuria. Histopathological evaluation detected nephropathy and atrophy of hematopoietic tissues/organs, mucosa of the intestinal tract and male genital tract. Cardiac lesions including chronic inflammation, endocardial hyperplasia, hemorrhage and myxomatous changes were evident in hematoxylin and eosin stains, and evaluation of semi-thin sections showed the presence of dose-related vacuolation in the atrial and ventricular cardiomyocytes. Cardiac troponin levels were increased in the high-dose group, but there was no direct correlation to the severity of the histopathological lesions. This study confirms that the Göttingen minipig has a comparable toxicity profile to humans and considering its anatomical, physiological, genetic and biochemical resemblance to humans, it should be considered as the non-rodent species of choice for studies on doxorubicin toxicity. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26614124

  15. Development of protocols for chronic toxicity testing of Pacific marine species

    SciTech Connect

    Langdon, C.J.; Seim, W.K.; Hoffman, R.L.; Weber, L.

    1990-03-01

    The development of a year-round capability for conducting short-term toxicity tests for estimating chronic-effect levels of toxic materials with a native Pacific coast fish and a native Pacific coast mysid shrimp was the goal of the project. In order to achieve acceptable sensitivity as a surrogate for chronic toxicity tests, targeting the reproductive portion of the mysid life cycle and all or part of the embryonic, larval, or early post-larval portion of the fish life cycle was deemed necessary. This targeting is consistent with conclusions based upon earlier work in developing similar tests with Atlantic coast, Gulf coast, and freshwater fish and invertebrates.

  16. Comparative evaluation of acute and chronic toxicities of CuO nanoparticles and bulk using Daphnia magna and Vibrio fischeri.

    PubMed

    Rossetto, Ana Letícia de O F; Melegari, Silvia Pedroso; Ouriques, Luciane Cristina; Matias, William Gerson

    2014-08-15

    Copper oxide (CuO) has various applications, as highlighted by the incorporation of this compound as a biocide of antifouling paints for coating ships and offshore oil platforms. The objective of this study was to evaluate and compare the aquatic toxicity of CuO nanoparticles (NPs) and microparticles (MPs) through acute and chronic toxicity tests with the freshwater microcrustacean Daphnia magna and an acute toxicity test with the bioluminescent marine bacteria Vibrio fischeri. Acute toxicity results for D. magna in tests with CuO NPs (EC50, 48 h=22 mg L(-1)) were ten times higher than those for tests with CuO MPs (EC50, 48 h=223.6 mg L(-1)). In both periods of exposure of V. fischeri, the CuO NPs (EC50, 15m 248±56.39 - equivalent to 12.40%; EC50, 30 m 257.6±30.8 mg L(-1) - equivalent to 12.88%) were more toxic than the CuO MPs (EC50, 15m 2404.6±277.4 - equivalent to 60.10%; EC50, 30 m 1472.9±244.7 mg L(-1) - equivalent to 36.82%). In chronic toxicity tests, both forms of CuO showed significant effects (p<0.05) on the growth and reproduction parameters of the D. magna relative to the control. Additionally, morphological changes, such as lack of apical spine development and malformed carapaces in D. magna, were observed for organisms after the chronic test. The toxicity results demonstrate that CuO NPs have a higher level of toxicity than CuO MPs, emphasizing the need for comparative toxicological studies to correctly classify these two forms of CuO with identical CAS registration numbers. PMID:24907615

  17. Identifying the cause of toxicity in an algal whole effluent toxicity study - an unanticipated toxicant.

    PubMed

    Naddy, Rami B; Tapp, Kelly; Rehner, Anita B; Pillard, David A; Schrage, Laura

    2011-10-01

    Toxicity was observed in whole effluent toxicity (WET) studies with the freshwater alga, Pseudokirchneriella subcapitata, in three consecutive monthly studies, (NOEC=50-75%). Toxicity was not observed to Ceriodaphnia dubia or the fathead minnow, Pimephales promelas in concurrent studies. Selected toxicity identification evaluation (TIE) tests were conducted in a tiered approach to eliminate possible toxicants and progressively identify the causative agent. Filtration following alkaline adjustment (pH 10 or 11) was effective in eliminating significant growth effects and also reduced phosphate concentration. The TIE studies confirmed that the observed effluent toxicity was caused by excess ortho-phosphate in the effluent not by overstimulation or related to unfavorable N:P ratios; but due to direct toxicity. The 96-h 25% inhibition concentration (IC25) of ortho-phosphate to P. subcapitata was 3.4 mg L⁻¹ while the maximum acceptable toxicant concentration was 4.8 mg L⁻¹. This study illustrates the value of multi-species testing and also provides an example of an effective TIE using algae identifying an unanticipated toxicant. PMID:21840029

  18. Anticholinesterase (DFP) toxicity antagonism by chronic donepezil: a potential nerve agent treatment.

    PubMed

    Janowsky, David S; Davis, John M; Overstreet, David H

    2005-08-01

    Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and toxicity of these agents. This study evaluated the effects of pretreatment with the oral cholinesterase inhibitor and anti-Alzheimer's agent, donepezil (Aricept) on the hypokinetic, hypothermic and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in adult Sprague-Dawley rats. Donepezil (2 mg/kg), given acutely (30 min pretreatment) or chronically (10 daily treatments), significantly antagonized the hypothermia, hypoactivity and diarrhea induced by DFP (1.25 mg/kg) administration. The effects were most prominent 4 and 6 h after the injection of DFP and some protection was observed even when the last treatment of the chronic donepezil protocol was given 24 h before the DFP injection. Although these phenomena are not the same as lethality, they may be parallel phenomena, and our results may have therapeutic implications for the treatment of nerve agent toxicity. PMID:16054679

  19. Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats.

    PubMed

    Nair, R S; Auletta, C S; Schroeder, R E; Johannsen, F R

    1990-10-01

    Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high-dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of

  20. Development of Quantitative Structure-Activity Relationship Models for Predicting Chronic Toxicity of Substituted Benzenes to Daphnia Magna.

    PubMed

    Fan, Deling; Liu, Jining; Wang, Lei; Yang, Xianhai; Zhang, Shenghu; Zhang, Yan; Shi, Lili

    2016-05-01

    The chronic toxicity of anthropogenic molecules such as substituted benzenes to Daphnia magna is a basic eco-toxicity parameter employed to assess their environmental risk. As the experimental methods are laborious, costly, and time-consuming, development in silico models for predicting the chronic toxicity is vitally important. In this study, on the basis of five molecular descriptors and 48 compounds, a quantitative structure-property relationship model that can predict the chronic toxicity of substituted benzenes were developed by employing multiple linear regressions. The correlation coefficient (R (2)) and root-mean square error (RMSE) for the training set were 0.836 and 0.390, respectively. The developed model was validated by employing 10 compounds tested in our lab. The R EXT (2) and RMSE EXT for the validation set were 0.736 and 0.490, respectively. To further characterizing the toxicity mechanism of anthropogenic molecules to Daphnia, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were developed. PMID:27016939

  1. Zebrafish reproductive toxicity induced by chronic perfluorononanoate exposure.

    PubMed

    Zhang, Wei; Sheng, Nan; Wang, Minhui; Zhang, Hongxia; Dai, Jiayin

    2016-06-01

    Perfluoroalkyl acids (PFAAs) are a group of anthropogenic compounds that have been widely used in consumer products for over 50 years. One of the most dominant PFAAs is perfluorononanoate (PFNA), a compound detected ubiquitously in aquatic ecosystems. While PFNA is suspected of being an endocrine disruptor, the mechanisms behind PFNA-induced reproductive disorders are poorly understood. The aim of this study was to investigate the reproduction-related effects and possible mechanisms of PFNA on adult zebrafish (Danio rerio) following 180 days of exposure at different concentrations (0.01, 0.1, 1mg/L). PFNA concentration in the gonads of zebrafish was tested by HPLC-MS/MS after chronic exposure to study possible inconsistent accumulation between the genders. The results showed that the accumulation of PFNA in the male gonads was almost one-fold higher than that in the female gonads, indicating a possible higher PFAA gonad burden for male zebrafish. Significant reductions in the male gonadosomatic index (GSI) and female egg production were observed. In addition, the decreased 72h hatching rate displayed an evident dosage effect, indicating that maternal exposure to PFNA might impair offspring developmental success. To investigate how PFNA exposure affects the hypothalamic-pituitary-gonadal-liver axis (HPGL axis), the transcriptional levels of genes were measured by real-time PCR. The disrupted expression of genes, such as ERα, ERβ, FSHR, LHR, StAR, and 17βHSD, indicated the possible interference of PFNA on the HPGL axis function and sex hormone synthesis. Furthermore, testosterone (T) and estradiol (E2) levels in serum and VTG content in the liver were detected to clarify the influences of PFNA on sex hormone levels. Except for the increase in serum estrogen levels, as an estrogen analogue, PFNA also induced the synthesis of biomarker protein vitellogenin (VTG) in the adult male liver. The results of this study indicate that chronic exposure to PFNA can lead to

  2. METHODS FOR AQUATIC TOXICITY IDENTIFICATION EVALUATIONS: PHASE III TOXICITY CONFIRMATION PROCEDURES FOR SAMPLES EXHIBITING ACUTE AND CHRONIC TOXICITY

    EPA Science Inventory

    In 1989, the guidance document for acutely toxic effluents titled Methods for Aquatic Toxicity Identification Evaluations: Phase III Toxicity Confirmation Procedures was published (EPA, 1989D)This manual and its companion documents (EPA, 1991A; EPA, 1992; EPA, 1993A) are intended...

  3. The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

    PubMed

    Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

    2016-05-01

    The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe. PMID:26335781

  4. Effects of chronic toxicity on threshold food concentrations

    SciTech Connect

    Cecchine, G.A.; Snell, T.W.

    1995-12-31

    Food shortage and toxicant stress have been proposed separately as structuring factors for zooplankton communities. How these factors interact to affect zooplankton remains poorly understood. The amount of food ingested by filter feeders depends upon food concentration, and a threshold concentration exists below which population growth is zero. A standard 2-d population growth test was used to determine whether toxicant stress altered the food threshold of the freshwater rotifer Brachionus calyciflorus. Threshold toxicant concentrations resulting in zero population growth rate and the NOEC were also compared at starving and abundant food conditions. Nutritional requirements were related to toxic exposure. For example, the threshold concentration of sodium pentachlorophenate (PCP) was 1.5 times lower at low food concentrations (0.3 million Nannochloris cells per milliliter) than at high food concentrations (3 million cells/ml). These results indicate that both factors must be considered in the validation of standard toxicity tests and their extrapolation to field conditions for ecologically meaningful predictions of toxicity.

  5. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity

    PubMed Central

    Deshpande, Laxmikant S.; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J.

    2014-01-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment. PMID:25172410

  6. Chronic TiO2 nanoparticle exposure to a benthic organism, Hyalella azteca: Impact of solar UV radiation and material surface coatings on toxicity

    EPA Science Inventory

    The present study examined the chronic toxicity of TiO2 nanoparticles (nano-TiO2) to a representative benthic species, Hyalella azteca, using an industry standard, P25, and a coated nano-TiO2 used in commercial products. There is limited information on the chronic effects of nano...

  7. Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and some notes on seasonal differences.

    PubMed

    Van den Brink, Paul J; Van Smeden, Jasper M; Bekele, Robel S; Dierick, Wiebe; De Gelder, Daphne M; Noteboom, Maarten; Roessink, Ivo

    2016-01-01

    Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid, thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some notes on the seasonality of the toxicity of imidacloprid to C. dipterum and 5 other invertebrate species. Imidacloprid and thiamethoxam showed equal acute and chronic toxicity to a winter generation of C. dipterum, whereas thiacloprid was approximately twice as toxic. The acute and chronic toxicity of imidacloprid was much higher for the C. dipterum summer generation than for the winter one. The acute toxicity differs by a factor of 20 for the 96-h 50% effective concentration (EC50) and by a factor of 5.4 for the chronic 28-d EC50. Temperature had only a slight effect on the sensitivity of C. dipterum to imidacloprid because we only found a factor of 1.7 difference in the 96-h EC50 between tests performed at 10 °C and 18 °C. The difference in sensitivity between summer and overwintering generations was also found for 3 other insect species. The results indicate that if the use and environmental fate of the 3 neonicotinoids are comparable, replacing imidacloprid by another neonicotinoid might not reduce the environmental impact on the mayfly nymph C. dipterum. The results also show the importance of reporting which generation is tested because sensitivity values of insects in the summer might be underestimated by the experiments performed with neonicotinoids and an overwintering population. PMID:26419398

  8. Acute, chronic and reproductive toxicity of complex cyanobacterial blooms in Daphnia magna and the role of microcystins.

    PubMed

    Smutná, Marie; Babica, Pavel; Jarque, Sergio; Hilscherová, Klára; Maršálek, Blahoslav; Haeba, Maher; Bláha, Ludek

    2014-03-01

    Toxic cyanobacterial blooms are a global threat to human health and aquatic biota. While the ecotoxicity of cyanobacterial toxins such as microcystins has been studied extensively, little is known about the risks they pose in the wild, i.e. within complex biomasses. In this work, crustaceans (Daphnia magna) were exposed to varying concentrations (0-405 mg d.w L(-1)) of eight complex cyanobacterial water bloom samples in a series of acute (48 h) and chronic (21 day) toxicity experiments. Further acute and chronic exposure assays were performed using aqueous extracts of the crude biomass samples and two fractions prepared by solid phase extraction (SPE) of the aqueous extracts. The cyanobacterial biomasses differed with respect to their dominant cyanobacterial species and microcystin contents. High acute toxicity was observed for 6 of the 8 crude biomass samples. Chronic exposure assays were performed using one complex biomass sample and its various subsamples/fractions. The complex biomass, the crude aqueous extract, and the microcystin-free SPE permeate all elicited similar and significant lethal effects, with LC50 values of around 35.6 mg biomass d.w L(-1) after 21 days. The cyanobacterial biomass samples also affected reproductive health, significantly increasing the time to the first brood (LOEC = 45 mg d.w L(-1) exposure) and inhibiting fecundity by 50% at 15 mg d.w L(-1). Conversely, the microcystin-containing C18-SPE eluate fraction had only weak effects in the chronic assay. These results indicate that cyanobacterial water blooms are highly toxic to zooplankton (both acutely and chronically) at environmentally relevant concentrations. However, the effects observed in the acute and chronic assays were independent of the samples' microcystin contents. Our results thus point out the importance of other cyanobacterial components such as lipopolysaccharides, various peptides and depsipeptides, polar alkaloid metabolites or other unidentified metabolites in the

  9. Changes of chemical chronic toxicity to Daphnia magna under different food regimes.

    PubMed

    Pavlaki, Maria D; Ferreira, Abel L G; Soares, Amadeu M V M; Loureiro, Susana

    2014-11-01

    In aquatic ecosystems several stressors may act together and affect the life traits of organisms. Pesticide runoffs are usually associated with high inputs of organic matter and depletion of oxygen in aquatic systems. This study aimed at combining anthropogenic stress (chemicals) and natural stress (food availability) and evaluates their joint effect to the life traits of Daphnia magna. The neonicotinoid insecticide imidacloprid and the heavy metal nickel chloride were used and a 21 d chronic test was carried out to obtain reproduction and growth data. The conceptual model Independent action, usually used for assessing response patterns in chemical mixtures, was used for data interpretation. Results showed an increase in the reproduction and growth pattern of D. magna as food levels increased. Both chemicals significantly impaired the reproduction as well as the somatic growth of the organism while the same happened with food concentrations lower than 3×10(5) cells/mL. It was also observed that food availability did not change the toxicity of imidacloprid and nickel chloride when food levels were higher than 3×10(5) cells/mL. When combined with low food levels, imidacloprid showed a slight increase in toxicity, showing that daphnids become more sensitive with reduced food availability, however in a non-significant way. However, toxicity of nickel appeared to be independent of the food level. Both chemicals induced mortality to the organisms exposed in the absence of food only at the end of the test. PMID:25164202

  10. Some biological aspects of Mysidopsis juniae (Crustacea:Mysidacea) and its use in chronic toxicity tests

    SciTech Connect

    Badaro-Pedroso, C. Nipper, M.G.

    1995-12-31

    As part of the joint effort to develop marine toxicity tests with organisms abundant at the Brazilian coast, some aspects for the laboratory culture of M. juniae and its sensitivity to single chemicals were studied. Organisms fed a mixture of brine shrimp (Artemia sp.) nauplii and the microalgae Isochrysis galbana reached sexual maturity 10 days before animals fed brine shrimp nauplii only. Under best conditions, sexual maturity was reached on the 9th--11th day and newborn mysids hatched on the 16th--18th day, Short-term chronic toxicity tests were initiated with 7-day old mysids and exposure time was 11 days, with growth (length and dry weight) as test endpoints. Experiments were undertaken with zinc, copper, and ammonia. Zinc did not affect the organisms at concentrations between 0.018 and 0.1 mg/L, which were one order of magnitude lower than the average 96-h; LC50 value. The NOEC and LOEC values were the same for length and weight in some tests with copper and ammonia (Cu: 0.006 and 0.015 mg/L; NH{sub 3}: 0.32 and 0.87 mg/L, respectively), but revealed length as a more sensitive endpoint than weight in others (length NOEC and LOEC: 0.23 and 0.53 mgNH{sub 3}/L; weight: 0.53 and 0.99 mgNH{sub 3}/L, respectively). The authors speculate that this could be caused by time-dependent variations in the lipid content of the organisms. Length would be a steadier and more reliable endpoint for chronic toxicity tests with M. juniae. The results show that the method has potential applications for the evaluation and monitoring of contaminated marine systems along the Brazilian coast.

  11. Comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukemia: an ECOG study. Part I: total body irradiation-response and toxicity

    SciTech Connect

    Rubin, P.; Bennent, J.M.; Begg, C.; Bozdech, M.J.; Silber, R.

    1981-12-01

    Twenty-six evaluable patients were entered into two fractionated total body irradiation (TBI) programs; 11 patients received a course of 150 rad TBI (x 3 if tolerated) and 15 patients received a lower dose course of 50 rad (x 3 if tolerated). Complete remissions (CR) were not produced by either course; however, the higher dose course (Plan I) yielded a partial response (PR) rate of 73%, while the lower dose course yielded a PR of 47%. Although fraction size seemed trivial in both TBI plans, an unexpected high degree of hematologic toxicity was encountered, and was parallel to the response rates: in Plan I 73% of patients experienced severe to life-threatening depression of platelets, or granulocytes, whereas in Plan II this rate was 47%. This was of short duration with rapid return of blood counts to normal levels. One death can be attributed to TBI. The chemotherapy arm of the study demonstrated superiority in terms of complete responses. Twenty-three percent of patients treated by cholrambucil and prednisone attained CR, in contrast to 0% of TBI patients. PR for chemotherapy was similar to that obtained with TBI. Chemotherapy also proved superior in terms of overall response rate, number of patients in remission, and in the median duration of response, but not in the median duration of survival. Fractional TBI techniques for active chronic lymphocytic leukemia (CLL) should be interrupted when the platelet count dips below 100,000 and the granulocyte count is lower than 2,000. Future studies should continue TBI radiation therapy and chemotherapy.

  12. Development of a chronic sediment toxicity test for marine benthic amphipods

    SciTech Connect

    DeWitt, T.H.; Redmond, M.S.; Sewall, J.E.; Swartz, R.C.

    1992-12-01

    The results of the research effort culminated in the development of a research method for assessing the chronic toxicity of contaminated marine and estuarine sediments using the benthic amphipod, Leptocheirus plumulosus. The first chapter describes the efforts at collecting, handling, and culturing four estuarine amphipods from Chesapeake Bay, including L. plumulosus. This chapter includes maps of the distribution and abundance of these amphipods within Chesapeake Bay and methodologies for establishing cultures of amphipods which could be readily adopted by other laboratories. The second chapter reports the development of acute and chronic sediment toxicity test methods for L. plumulosus, its sensitivity to non-contaminant environmental variables, cadmium, two polynuclear aromatic hydrocarbons, and contaminated sediment from Baltimore Harbor, MD. The third chapter reports the authors attempts to develop a chronic sediment toxicity test with Ampelisca abdita.

  13. ENANTIOSELECTIVE CHRONIC TOXICITY OF FIPRONIL TO CERIODAPHNIA DUBIA

    EPA Science Inventory

    Fipronil is a phenylpyrazole pesticide that has greatly increased in popularity in recent years. As a chiral molecule, fipronil is released into the environment as a 1:1 mixture (called a racemate) of its two enantiomers. Previous toxicity work has indicated that the enantiomer...

  14. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., growth) are the criteria of toxicity. (3) EC 50 means that experimentally derived concentration of test substance in dilution water that is calculated to affect 50 percent of a test population during continuous... same dilution water, conditions, procedures and daphnids from the same population (culture...

  15. ACUTE AND CHRONIC PARATHION TOXICITY TO FISH AND INVERTEBRATES

    EPA Science Inventory

    Acute and chronic aquatic bioassays were conducted with a variety of organisms using parathion (0,0-diethyl 0-(p-nitrophenyl) phosphorothioate) as the challenge compound. Acute LC50 values ranged from a low of 0.38 micrograms/l in invertebrates to a high of 2.0 mg/l in freshwater...

  16. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during chronic... mysids in each chamber shall be recorded on days 7, 14, 21, and 28 of the test. At the time when sexual... treatment groups. This time cannot be specified because of possible delays in sexual maturation of...

  17. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during chronic... mysids in each chamber shall be recorded on days 7, 14, 21, and 28 of the test. At the time when sexual... treatment groups. This time cannot be specified because of possible delays in sexual maturation of...

  18. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substance. In this test, mortality, number of young per female and growth are used as measures of chronic... kill 50 percent of a test population during continuous exposure over a specified period of time. (6... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during...

  19. 40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substance. In this test, mortality, number of young per female and growth are used as measures of chronic... kill 50 percent of a test population during continuous exposure over a specified period of time. (6... concentration-response curves, LC50 values, and effects of a chemical on growth and reproduction during...

  20. Full-life chronic toxicity of sodium salts to the mayfly Neocloeon triangulifer in tests with laboratory cultured food.

    PubMed

    Soucek, David J; Dickinson, Amy

    2015-09-01

    Although insects occur in nearly all freshwater ecosystems, few sensitive insect models exist for use in determining the toxicity of contaminants. The objectives of the present study were to adapt previously developed culturing and toxicity testing methods for the mayfly Neocloeon triangulifer (Ephemeroptera: Baetidae), and to further develop a method for chronic toxicity tests spanning organism ages of less than 24 h post hatch to adult emergence, using a laboratory cultured diatom diet. The authors conducted 96-h fed acute tests and full-life chronic toxicity tests with sodium chloride, sodium nitrate, and sodium sulfate. The authors generated 96-h median lethal concentrations (LC50s) of 1062 mg Cl/L (mean of 3 tests), 179 mg N-NO3 /L, and 1227 mg SO4 /L. Acute to chronic ratios ranged from 2.1 to 6.4 for chloride, 2.5 to 5.1 for nitrate, and 2.3 to 8.5 for sulfate. The endpoints related to survival and development time were consistently the most sensitive in the tests. The chronic values generated for chloride were in the same range as those generated by others using natural foods. Furthermore, our weight-versus-fecundity plots were similar to those previously published using the food culturing method on which the present authors' method was based, indicating good potential for standardization. The authors believe that the continued use of this sensitive mayfly species in laboratory studies will help to close the gap in understanding between standard laboratory toxicity test results and field-based observations of community impairment. PMID:25918877

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

    PubMed Central

    Flohr, Letícia; de Castilhos Júnior, Armando Borges; Matias, William Gerson

    2012-01-01

    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. PMID:22619632

  2. Protective Effects of Lactobacillus plantarum CCFM8610 against Chronic Cadmium Toxicity in Mice Indicate Routes of Protection besides Intestinal Sequestration

    PubMed Central

    Zhai, Qixiao; Wang, Gang; Zhao, Jianxin; Liu, Xiaoming; Narbad, Arjan; Chen, Yong Q.; Zhang, Hao; Chen, Wei

    2014-01-01

    Our previous study confirmed the ability of Lactobacillus plantarum CCFM8610 to protect against acute cadmium (Cd) toxicity in mice. This study was designed to evaluate the protective effects of CCFM8610 against chronic Cd toxicity in mice and to gain insights into the protection mode of this strain. Experimental mice were divided into two groups and exposed to Cd for 8 weeks via drinking water or intraperitoneal injection. Both groups were further divided into four subgroups, control, Cd only, CCFM8610 only, and Cd plus CCFM8610. Levels of Cd were measured in the feces, liver, and kidneys, and alterations of several biomarkers of Cd toxicity were noted. The results showed that when Cd was introduced orally, cotreatment with Cd and CCFM8610 effectively decreased intestinal Cd absorption, reduced Cd accumulation in tissue, alleviated tissue oxidative stress, reversed hepatic and renal damage, and ameliorated the corresponding histopathological changes. When Cd was introduced intraperitoneally, administration of CCFM8610 did not have an impact on tissue Cd accumulation or reverse the activities of antioxidant enzymes. However, CCFM8610 still offered protection against oxidative stress and reversed the alterations of Cd toxicity biomarkers and tissue histopathology. These results suggest that CCFM8610 is effective against chronic cadmium toxicity in mice. Besides intestinal Cd sequestration, CCFM8610 treatment offers direct protection against Cd-induced oxidative stress. We also provide evidence that the latter is unlikely to be mediated via protection against Cd-induced alteration of antioxidant enzyme activities. PMID:24771031

  3. The joint effects of sulfonamides and quorum sensing inhibitors on Vibrio fischeri: Differences between the acute and chronic mixed toxicity mechanisms.

    PubMed

    Wang, Ting; Liu, Yuewei; Wang, Dali; Lin, Zhifen; An, Qingqing; Yin, Chunsheng; Liu, Yin

    2016-06-01

    Quorum sensing inhibitors (QSIs) are considered to be promising antibiotic alternatives and will be increasingly exposed to the environment together with antibiotics after their research and development process; it is therefore necessary to study the joint effects of QSIs and antibiotics. In this study, single and mixed toxicity of sulfonamide (SAs) and QSIs under acute and chronic conditions and their corresponding toxicity mechanisms were investigated. The results indicated that the acute joint effect was extremely complex, ranging from an antagonistic to synergistic response, while the chronic joint effect was primarily an antagonistic response. Using a molecular docking and regression model, we found that the acute joint effect could be determined by the hydrion's, ability to be oxidized, as well as the binding energy. The chronic joint effect was primarily an antagonistic response, which was due to the QSI competing against AHL for luxR generated by SAs, leading to negative effects of the QSI-luxR complexes on luxI. This phenomenon eventually weakened the stimulatory effect caused by SAs. Finally, the main differences between acute and chronic mixtures were analyzed: (1) The target protein was different between acute and chronic toxicity mixtures, and (2) effective concentration in acute and chronic toxicity mixtures was also different. These deep insights into mixed toxicity mechanisms will play an important role in the study of antibiotic resistance genes in response to antibiotic replacements. PMID:26897575

  4. Unraveling the chronic toxicity of lead: an essential priority for environmental health.

    PubMed Central

    Todd, A C; Wetmur, J G; Moline, J M; Godbold, J H; Levin, S M; Landrigan, P J

    1996-01-01

    Although population exposure to lead has declined, chronic lead toxicity remains a major public health problem in the United States affecting millions of children and adults. Important gaps exist in knowledge of the pathophysiology of chronic lead intoxication. These gaps have impeded development of control strategies. To close current gaps in knowledge of chronic lead toxicity, we propose an integrated, multidisciplinary, marker-based research program. This program combines a) direct measurement of individual lead burden by 109Cd X-ray fluorescence analysis of lead in bone, b) determination of ALA-D phenotype, an index of individual susceptibility to lead, and c) assessments of subclinical injury produced by lead in the kidneys, nervous system and, reproductive organs. Data from this research will provide answers to questions of great public health importance: a) Are current environmental and occupational standards adequate to prevent chronic lead intoxication? b) is lead mobilized from the skeleton during pregnancy or lactation to cause fetal toxicity? c) Is lead mobilized from bone during menopause to cause neurotoxicity? d) What is the significance of genetic variation in determining susceptibility to lead? e) What is the contribution of lead to hypertension, renal disease, chronic neurodegenerative disease or declining sperm counts? f) Is chelation therapy effective in reducing body lead burden in persons with chronic overexposure to lead? PMID:8722118

  5. Acute and chronic toxicity of uranium compounds to Ceriodaphnia-Daphnia dubia

    SciTech Connect

    Pickett, J.B.; Specht, W.L.; Keyes, J.L.

    1993-03-31

    A study to determine the acute and chronic toxicity of uranyl nitrate, hydrogen uranyl phosphate, and uranium dioxide to the organism Ceriodaphnia dubia was conducted. The toxicity tests were conducted by two independent environmental consulting laboratories. Part of the emphasis for this determination was based on concerns expressed by SCDHEC, which was concerned that a safety factor of 100 must be applied to the previous 1986 acute toxicity result of 0.22 mg/L for Daphnia pulex, This would have resulted in the LETF release limits being based on an instream concentration of 0.0022 mg/L uranium. The NPDES Permit renewal application to SCDHEC utilized the results of this study and recommended that the LETF release limit for uranium be based an instream concentration of 0.004 mg/L uranium. This is based on the fact that the uranium releases from the M-Area LETF will be in the hydrogen uranyl phosphate form, or a uranyl phosphate complex at the pH (6--10) of the Liquid Effluent Treatment Facility effluent stream, and at the pH of the receiving stream (5.5 to 7.0). Based on the chronic toxicity of hydrogen uranyl phosphate, a lower uranium concentration limit for the Liquid Effluent Treatment Facility outfall vs. the existing NPDES permit was recommended: The current NPDES permit ``Guideline`` for uranium at outfall M-004 is 0.500 mg/L average and 1.0 mg/L maximum, at a design flowrate of 60 gpm. It was recommended that the uranium concentration at the M-004 outfall be reduced to 0.28 mg/L average, and 0.56 mg/L, maximum, and to reduce the design flowrate to 30 gpm. The 0.28 mg/L concentration will provide an instream concentration of 0.004 mg/L uranium. The 0.28 mg/L concentration at M-004 is based on the combined flows from A-014, A-015, and A-011 outfalls (since 1985) of 1840 gpm (2.65 MGD) and was the flow rate which was utilized in the 1988 NPDES permit renewal application.

  6. Sensitivity of mottled sculpins (Cottus bairdi) and rainbow trout (Onchorhynchus mykiss) to acute and chronic toxicity of cadmium, copper, and zinc

    USGS Publications Warehouse

    Besser, J.M.; Mebane, C.A.; Mount, D.R.; Ivey, C.D.; Kunz, J.L.; Greer, I.E.; May, T.W.; Ingersoll, C.G.

    2007-01-01

    Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 ??g/L for Missouri sculpins and 37 ??g/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 ??g/L (Missouri) and 1.9 ??g/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 ??g/L) than Missouri sculpins (chronic ChV = 219 ??g/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested. ?? 2007 SETAC.

  7. Sensitivity of mottled sculpins (Cottus bairdi) and rainbow trout (Onchorhynchus mykiss) to acute and chronic toxicity of cadmium, copper, and zinc

    USGS Publications Warehouse

    Besser, John M.; Mebane, Christopher A.; Mount, David R.; Ivey, Chris D.; Kunz, James L.; Greer, I. Eugene; May, Thomas W.; Ingersoll, Christopher G.

    2007-01-01

    Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 μg/L for Missouri sculpins and 37 μg/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 μg/L (Missouri) and 1.9 μg/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 μg/L) than Missouri sculpins (chronic ChV = 219 μg/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested.

  8. Acute and chronic toxicities of zinc pyrithione alone and in combination with copper to the marine copepod Tigriopus japonicus.

    PubMed

    Bao, Vivien W W; Lui, Gilbert C S; Leung, Kenneth M Y

    2014-12-01

    Zinc pyrithione (ZnPT) is a widely used booster biocide in combination with copper (Cu) in antifouling paints as a substitute for tributyltin. The co-occurrence of ZnPT and Cu in coastal marine environments is therefore very common, and may pose a higher risk to marine organisms if they can result in synergistic toxicity. This study comprehensively investigated the combined toxicity of ZnPT and Cu, on the marine copepod Tigriopus japonicus, for the first time, based on both 96-h acute toxicity tests using adult copepods and chronic full-life cycle tests (21 d) using nauplii <24-h old. As ZnPT has been reported to be easily trans-chelated to copper pyrithione (CuPT) in the presence of Cu, the acute toxicities of CuPT alone and in combination with Cu on adult copepods were also assessed. Our results showed that ZnPT and Cu exhibited a strong synergistic toxic effect on the copepod in both acute and chronic tests. During the acute test, the mortalities of adult copepods increased dramatically even with an addition of Cu at concentrations as low as 1-2 μg/L compared with those exposed to ZnPT alone. Severe chronic toxicities were further observed in the copepods exposed to ZnPT-Cu mixtures, including a significant increase of naupliar mortality, postponing of development from naupliar to copepodid and from copepodid to adult stage, and a significant decrease of intrinsic population growth when compared with those of copepods exposed to ZnPT or Cu alone. Such synergistic effects might be partly attributable to the formation of CuPT by the trans-chelation of ZnPT and Cu, because CuPT was found to be more toxic than ZnPT based on the acute toxicity results. Mixtures of CuPT and Cu also led to synergistic toxic effects to the copepod, in particular at high Cu concentrations. A novel non-parametric response surface model was applied and it proved to be a powerful method for analysing and predicting the acute binary mixture toxicities of the booster biocides (i.e., ZnPT and

  9. TAGE (toxic AGEs) hypothesis in various chronic diseases.

    PubMed

    Takeuchi, M; Yamagishi, S

    2004-01-01

    The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified proteins and peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that glyceraldehyde-derived AGEs (AGEs-2) and glycolaldehyde-derived AGEs (AGE-3) have diverse biological activities on vascular wall cells, mesangial cells, Schwann cells, malignant melanoma cells and cortical neurons. We also demonstrated for the first time that acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not non-toxic AGEs (N-carboxymethyllysine, pentosidine, pyrraline etc.) are likely to play an important role in the pathophysiological processes associated with AGEs formation. PMID:15288366

  10. Chronic oral DDT toxicity in juvenile coho and chinook salmon

    USGS Publications Warehouse

    Buhler, Donald R.; Rasmusson, Mary E.; Shanks, W.E.

    1969-01-01

    Technical and p,p′-DDT was incorporated into test diets and fed to juvenile chinook and coho salmon for periods as long as 95 days. Pure p,p′-DDT was slightly more toxic to young salmon than was the technical DDT mixture. Chinook salmon appeared to be 2–3 times more sensitive to a given concentration of DDT in the diet than were coho salmon. The size of the fish greatly influenced toxicity, smaller younger fish being more susceptible to a given diet than larger older fish. The dose of DDT accumulated within the median survival time ranged from 27–73 mg/kg for chinook salmon and from 56–72 mg/kg for coho salmon. The extrapolated 90-dose LD50 (Hayes, 1967) for young chinook and coho salmon were 0.0275 and 0.064 mg/kg/day, respectively. Liver size decreased on prolonged feeding with DDT, and carcass lipid content was increased. A severe surface ulceration of the nose region appeared in coho salmon fed DDT over long periods. In addition, an interesting localized degeneration of the distal convoluted tubule was observed in the kidney of coho salmon receiving DDT.

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

    EPA Science Inventory

    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 ...

  12. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  13. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  14. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Summary of guidelines for determining chronic toxicity. 1500.135 Section 1500.135 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS § 1500.135 Summary of...

  15. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  16. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... toxicity may be found at 16 CFR 1500.3(c)(2).) The following discussions are intended to help clarify the... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... require that a causal relationship between exposure to an agent and cancer be established. This...

  17. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  18. CHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60 and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23,...

  19. Comparison of Brachionus calyciflorus 2-d and Microtox{reg{underscore}sign} chronic 22-H tests with Daphnia magna 21-d test for the chronic toxicity assessment of chemicals

    SciTech Connect

    Radix, P.; Leonard, M.; Papantoniou, C.; Roman, G.; Saouter, E.; Gallotti-Schmitt, S.; Thiebaud, H.; Vasseur, P.

    1999-10-01

    The Daphnia magna 21-d test may be required by European authorities as a criterion for the assessment of aquatic chronic toxicity for the notification of new substances. However, this test has several drawbacks. It is labor-intensive, relatively expensive, and requires the breeding of test organisms. The Brachionous calyciflorus 2-d test and Microtox chronic 22-h test do not suffer from these disadvantages and could be used as substitutes for the Daphnia 21-d test for screening assays. During this study, the toxicity of 25 chemicals was measured using both the microtox chronic toxicity and B. calyciflorus 2-d tests, and the no-observed-effect concentrations (NOECs) were compared to the D. magna 21-d test. The Brachionus test was slightly less sensitive than the Daphnia test, but the correlation between the two tests was relatively good (r{sup 2} = 0.54). The B. calyciflorus 2-d test, and to a lesser extent the Microtox chronic 22-h test, were able to predict the chronic toxicity values of the Daphnia 21-d test. They constitute promising cost-effective tools for chronic toxicity screening.

  20. Acute and chronic toxicity of selected disinfection byproducts to Daphnia magna, Cyprinodon variegatus, and Isochrysis galbana.

    PubMed

    Fisher, Daniel; Yonkos, Lance; Ziegler, Gregory; Friedel, Elizabeth; Burton, Dennis

    2014-05-15

    Ballast water treatment has become a major issue in the last decade due to the problem of invasive species transported and released by the uptake and discharge of ballast water for shipping operations. One of the important issues considering ballast water treatment is to determine whether treated ballast water, once discharged, is safe to the aquatic environment. The International Maritime Organization (IMO) Marine Environmental Protection Committee (MEPC) has determined that prior to approval of a ballast water management system, aquatic toxicity data must be available for both the active substance and relevant byproducts. Many proposed ballast water treatment systems use chlorine as the active ingredient. Although there are sufficient toxicity data concerning active substances such as chlorine, there are limited toxicity data concerning disinfection (halogenated) byproducts including dibromochloromethane, four haloacetic acids and sodium bromate. Acute and chronic toxicity were determined for these disinfection byproducts (DBPs). Acute toxicity values ranged from 96-h LC50s of 46.8 mg/l for Daphnia magna for both dibromochloromethane and sodium bromate to a 96-h LC50 of 376.4 mg/l for Cyprinodon variegatus for tribromoacetic acid. Acute Isochrysis galbana population growth effect values ranged from a 72-h EC10 of 39.9 mg/l for dichloroacetic acid to a 72-h EC50 of 15,954 mg/l for sodium bromate. Chronic toxicity mortality/reproduction effects values for D. magna ranged from a 21-d IC25 of 160.9 mg/l for tribromoacetic acid to a 21-d LOEC of 493.0 mg/l for trichloroacetic acid. Chronic toxicity mortality/growth values for C. variegatus ranged from a 32-d IC25 of 246.8 mg/l for trichloroacetic acid to a 32-d LOEC of 908.1 mg/l for tribromoacetic acid. I. galbana 96-h chronic population growth effects values ranged from an EC10 of 38.5 mg/l for trichloroacetic acid to an LOEC of 500.0 mg/l for tribromoacetic acid. Acute to chronic ratios for all of these

  1. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  2. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2015-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  3. Chronic toxicity of 2,4,6-trinitrotoluene to a marine polychaete and an estuarine amphipod

    SciTech Connect

    Green, A.; Moore, D.; Farrar, D.

    1999-08-01

    The chronic toxicity of sediment-associated 2,4,6-trinitrotoluene (TNT) to the marine polychaete Neanthes arenaceodentata and the estuarine amphipod Leptocheirus plumulosus was evaluated. Test organisms were exposed to sediments spiked with radiolabeled TNT for 28 d, after which time the endpoints of mortality, growth, and reproduction (L. plumulosus only) were assayed and compared against the TNT tissue concentrations as well as the TNT sediment concentrations. Survival was significantly reduced at a tissue concentration of 61 {micro}g TNT/g wet wt tissue in N. arenaceodentata and L. plumulosus with enhancement (significant for N. arenaceodentata) occurring at the lower TNT concentrations. Growth was significantly reduced at the highest TNT exposure of 10.0 {micro}g TNT/g wet wt tissue in L. plumulosus. Reproduction was significantly reduced at a tissue concentration of 6.3 {micro}g TNT/g wet wt tissue in L. plumulosus. The results of this study demonstrate that both N. arenaceodentata and L. plumulosus are sensitive to the presence of sediment-associated TNT and that more information is needed about the toxicity of TNT to benthic fauna to facilitate risk assessment and management of TNT-contaminated sites.

  4. Chronic Fluoride Toxicity and Myocardial Damage: Antioxidant Offered Protection in Second Generation Rats

    PubMed Central

    Basha, Mahaboob P.; Sujitha, N. S.

    2011-01-01

    This experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims. PMID:21976813

  5. Chronic toxicity of phenanthrene to the marine polychaete worm, Nereis (Neanthes) arenaceodentata

    SciTech Connect

    Emery, V.L. Jr.; Dillon, T.M.

    1996-02-01

    Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in the environment. While environmental concentrations are generally below acutely, lethal levels, chronic, low level exposures may result in subtle sublethal effects. PAHs accumulate in bottom sediments and may represent a hazard to the benthos. Polychaetes are important members of this community. The objective of this study is to evaluate the chronic sublethal effects of one PAH, phenanthrene (PHN), on the polychaete worm, Nereis arenaceodentata. PHN was selected because of its high toxicity to marine invertebrates relative to other PAHs. The response of bivalves to heavy metals and other toxins has usually been determined by observing valve position. Since mussels close their valves to avoid noxious stimuli, experimental delivery of chemicals is uncertain. To obtain constant results. Preston employed plastic spacers to hold the valves apart. This obviates the observation of valve position as an index of response, and some other method is required. Electromyography of intact mussels is one such index, and is shown to be a simple, effective and quantitative measurement of activity. Experiments are reported on the effects of added mercury on salt water and fresh water species. Parts of this Nvork have appeared in brief form.

  6. Multi-level assessment of chronic toxicity of estuarine sediments with the amphipod Gammarus locusta: II. Organism and population-level endpoints.

    PubMed

    Costa, Filipe O; Neuparth, Teresa; Correia, Ana D; Costa, Maria Helena

    2005-07-01

    This study aimed to test the performance of the amphipod Gammarus locusta (L.) in chronic sediment toxicity tests. It constitutes part of a multi-level assessment of chronic toxicity of estuarine sediments, integrating organism and population-level endpoints with biochemical markers responses. Here we account for organism and population-level effects, while biomarker responses were reported in a companion article. Five moderately contaminated sediments from Sado and Tagus estuaries were tested, comprising 3 muddy and 2 sandy sediments. These sediments either did not show acute toxicity or were diluted with control sediment as much as required to remove acute toxicity. Subsequent chronic tests consisted of 28-day exposures with survival, individual growth and reproductive traits as endpoints. Two of the muddy sediments induced higher growth rates in the amphipods, and improved reproductive traits. This was understood to be a consequence of the amount of organic matter in the sediment, which was nutritionally beneficial to the amphipods, while concurrently decreasing contaminant bioavailability. Biomarker responses did not reveal toxicant-induced stress in amphipods exposed to these sediments. One of the sandy sediments was acutely toxic at 50% dilution, but in contrast stimulated amphipod growth when diluted 75%. This was presumed to be an indication of a hormetic response. Finally the two remaining contaminated sediments showed pronounced chronic toxicity, affecting survival and reproduction. The sex ratio of survivors was highly biased towards females, and offspring production was severely impaired. The particulars of the responses of this amphipod were examined, as well as strengths versus limitations of the sediment test. This study illustrates the utility of this chronic test for toxicity assessment of contaminated estuarine sediments, with potential application all along Atlantic Europe. PMID:15649529

  7. Toxicity of sodium molybdate and sodium dichromate to Daphnia magna straus evaluated in acute, chronic, and acetylcholinesterase inhibition tests.

    PubMed

    Diamantino, T C; Guilhermino, L; Almeida, E; Soares, A M

    2000-03-01

    As a result of a widespread application in numerous industrial processes, chromium is a contaminant of many environmental systems. Chromium and their compounds are toxic to both invertebrates and vertebrates and, for this reason, there has been a search for suitable and less toxic alternatives. Molybdenum compounds have been studied as alternative to chromium compounds for some industrial applications. The toxicity of chromium is well known but the effects of molybdenum and molybdenum mining on natural populations and communities of freshwater invertebrates have not often been studied. However, chromium, and molybdenum (and their compounds) are included in the same list (List II) of European Union dangerous substances. In this study, the acute and chronic effects of sodium molybdate and sodium dichromate to Daphnia magna Straus were evaluated. Furthermore, in vitro and in vivo effects of these two metals on acetylcholinesterase (AChE) activity of D. magna Straus were investigated. LC(50) values determined at 48 h were 0.29 and 2847.5 mg L(-1) for chromium (as sodium dichromate) and molybdenum (as sodium molybdate), respectively. No significant in vitro effects of both metals on AChE were found. However, both toxicants inhibited AChE in vivo at concentrations under the respective 48-h LC(50) values. Both sodium dichromate and sodium molybdate inhibited the reproduction and growth of D. magna, but the concentrations inducing significant effects were different for the two chemicals. Sodium molybdate had significant lower toxicity to D. magna Straus than sodium dichromate. PMID:10702344

  8. Chronic lung inflammation in victims of toxic gas leak at Bhopal.

    PubMed

    Vijayan, V K; Sankaran, K; Sharma, S K; Misra, N P

    1995-02-01

    Bronchoalveolar lavage (BAL) studies in 20 patients at Bhopal, 1.3 +/- 0.4 yr and 2.7 +/- 0.6 yr after toxic gas exposure had revealed that the lower respiratory tract inflammation had progressed from initial macrophage alveolitis to macrophage-neutrophilic alveolitis. The interval between the two lavages was 1.4 +/- 0.6 yr. BAL studies in a new group of 24 patients 5.1 +/- 1.0 yr after exposure had confirmed chronic inflammation of the lower respiratory tract as evidenced by macrophage-neutrophilic alveolitis in these subjects as well. Clinical, radiographic and pulmonary function abnormalities were persistent in a proportion of subjects in both groups. Fibronectin (FN) levels were estimated in BAL fluid in 41 patients. Elevated FN levels were seen in 12 (29.3%) subjects and nine of these 12 had radiographic abnormalities. Severely exposed subjects (n = 30) had significantly higher BAL fibronectin levels compared to normal subjects and mild/moderately exposed subjects. Repeat FN estimations in BAL samples from 10 patients had revealed that five had abnormally high FN including three who had high FN on both occasions. The number of patients showing abnormal decline in pulmonary function was higher in patients with elevated FN than in patients with normal FN. Thus, persisting clinical, roentgenographic and ventilatory abnormalities, as well as macrophage-neutrophilic alveolitis along with abnormally elevated FN levels in a proportion of subjects, suggest the possibility that lung fibrosis can occur in subjects exposed to toxic gas at Bhopal. PMID:7708994

  9. 40 CFR 799.9410 - TSCA chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... morphological (pathological) effects. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... equipment. The study must be conducted in compliance with 40 CFR Part 792—Good Laboratory Practice...

  10. 40 CFR 799.9410 - TSCA chronic toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... morphological (pathological) effects. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... equipment. The study must be conducted in compliance with 40 CFR Part 792—Good Laboratory Practice...

  11. 40 CFR 799.9410 - TSCA chronic toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... morphological (pathological) effects. (c) Definitions. The definitions in section 3 of TSCA and in 40 CFR Part... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... equipment. The study must be conducted in compliance with 40 CFR Part 792—Good Laboratory Practice...

  12. Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia.

    PubMed

    Moslehi, Javid J; Deininger, Michael

    2015-12-10

    For most patients with chronic myeloid leukemia, tyrosine kinase inhibitors (TKIs) have turned a fatal disease into a manageable chronic condition. Imatinib, the first BCR-ABL1 TKI granted regulatory approval, has been surpassed in terms of molecular responses by the second-generation TKIs nilotinib, dasatinib, and bosutinib. Recently, ponatinib was approved as the only TKI with activity against the T315I mutation. Although all TKIs are associated with nonhematologic adverse events (AEs), experience with imatinib suggested that toxicities are typically manageable and apparent early during drug development. Recent reports of cardiovascular AEs with nilotinib and particularly ponatinib and of pulmonary arterial hypertension with dasatinib have raised concerns about long-term sequelae of drugs that may be administered for decades. Here, we review what is currently known about the cardiovascular toxicities of BCR-ABL1 TKIs, discuss potential mechanisms underlying cardiovascular AEs, and elucidate discrepancies between the reporting of such AEs between oncology and cardiovascular trials. Whenever possible, we provide practical recommendations, but we concede that cause-directed interventions will require better mechanistic understanding. We suggest that chronic myeloid leukemia heralds a fundamental shift in oncology toward effective but mostly noncurative long-term therapies. Realizing the full potential of these treatments will require a proactive rational approach to minimize long-term cardiovascular and cardiometabolic toxicities. PMID:26371140

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

    PubMed

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida; Nakamura, Celso Vataru

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg(-1). In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg(-1)). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered. PMID:23970938

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

    PubMed Central

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg−1). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered. PMID:23970938

  15. Overview of Chronic Oral Toxicity Values for Chemicals Present in Hydraulic Fracturing Fluids, Flowback, and Produced Waters.

    PubMed

    Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

    2016-05-01

    Concerns have been raised about potential public health effects that may arise if hydraulic fracturing-related chemicals were to impact drinking water resources. This study presents an overview of the chronic oral toxicity values-specifically, chronic oral reference values (RfVs) for noncancer effects, and oral slope factors (OSFs) for cancer-that are available for a list of 1173 chemicals that the United States (U.S.) Environmental Protection Agency (EPA) identified as being associated with hydraulic fracturing, including 1076 chemicals used in hydraulic fracturing fluids and 134 chemicals detected in flowback or produced waters from hydraulically fractured wells. The EPA compiled RfVs and OSFs using six governmental and intergovernmental data sources. Ninety (8%) of the 1076 chemicals reported in hydraulic fracturing fluids and 83 (62%) of the 134 chemicals reported in flowback/produced water had a chronic oral RfV or OSF available from one or more of the six sources. Furthermore, of the 36 chemicals reported in hydraulic fracturing fluids in at least 10% of wells nationwide (identified from EPA's analysis of the FracFocus Chemical Disclosure Registry 1.0), 8 chemicals (22%) had an available chronic oral RfV. The lack of chronic oral RfVs and OSFs for the majority of these chemicals highlights the significant knowledge gap that exists to assess the potential human health hazards associated with hydraulic fracturing. PMID:27050380

  16. An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (Salvelinus confluentus) and the rainbow trout (Onchorhyncus mykiss).

    PubMed

    Fairchild, J F; Feltz, K P; Sappington, L C; Allert, A L; Nelson, K J; Valle, J

    2009-05-01

    We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis. PMID:18784952

  17. An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (salvelinus confluentus) and the rainbow trout (onchorhyncus mykiss)

    USGS Publications Warehouse

    Fairchild, J.F.; Feltz, K.P.; Sappington, L.C.; Allert, A.L.; Nelson, K.J.; Valle, J.

    2009-01-01

    We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis. ?? 2008 Springer Science+Business Media, LLC.

  18. DICLOFENAC: NEW DATA ON CHRONIC TOXICITY AND BIOCONCENTRATION IN FISH

    PubMed Central

    Memmert, Ulrich; Peither, Armin; Burri, Roland; Weber, Klaus; Schmidt, Thomas; Sumpter, John P; Hartmann, Andreas

    2013-01-01

    Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug that is regularly detected in surface waters. To support a robust aquatic risk assessment, two early life stage (ELS) tests, compliant with the Organisation for Economic Co-operation and Development (OECD) test guideline 210, were conducted in rainbow trout and in zebrafish. Population relevant endpoints, such as hatching, growth, and survival, and in the trout study, histopathological effects in potential target organs, were examined. The bioconcentration of DCF in rainbow trout was measured in a separate study according to OECD test guideline 305. The bioconcentration factor (BCF) in rainbow trout remained below 10, demonstrating no relevant bioconcentration of DCF in fish. In the rainbow trout ELS test, the no observed effect concentration (NOEC) including histopathology was 320 µg/L. The effect of DCF on zebrafish growth was less clear, and the NOEC can be interpreted as 10 µg/L. However, for a number of reasons, the authors consider the moderately reduced growth of zebrafish exposed to concentrations of up to 320 µg/L not a repeatable, treatment-related effect of DCF. This leads us to a conclusion that DCF has, with high probability, no adverse effect on both fish species up to 320 µg/L. This NOEC indicates a sufficient safety margin for fish populations, because concentrations of DCF in European rivers are in the range of ng/L to low µg/L. Environ. Toxicol. Chem. 2013;32:442–452. © 2013 SETAC PMID:23325530

  19. Chronic toxicity of phosalone to rats: Effect on erythropoiesis

    SciTech Connect

    Reddy, S.J.; Reddy, D.C.; Kalarani, V.; Ramamurthi, R. )

    1989-12-01

    It is well known that organophosphorus insecticides (OPI) act as nerve poisons by blocking synaptic transmission in cholinergic part of the nervous system. Phosalone (0,0-diethyl-S-(6-chloro-1,3-benzoxozol-2(3H)-onylmethyl)phosphorodithioate), an OPI, is being extensively used to kill insect crop pests in this part of India. Studies on the effects of phosalone on physiology of vertebrates are very few. Prolonged exposure to phosalone has been reported to cause marked changes in body weight, liver weight and RBC of rats. Others reported a decrease in brain SDH activity of rat dosed with phosalone, and a decrease in brain acetylcholinesterase (AchE) activity of fish exposed to phosalone. However, the effect of multiple sublethal doses of phosalone on haemopoietic system of rat has not yet been fully evaluated. The present investigation is one such attempt over a 60 day period.

  20. Sub-chronic toxicity of gold nanoparticles in male mice

    PubMed Central

    Ajdary, Marziyeh; Ghahnavieh, Marziyeh Ziaee; Naghsh, Nooshin

    2015-01-01

    Background: Gold nanoparticles have many industrial applications; moreover, they are photothermic agents for clinical treatment of cancer. This study was provided to investigate the effects associated with different doses of applied gold nanoparticles by injection and contact procedures on the alterations of the serum levels and certain factors in male mice. Materials and Methods: 72 male mice were randomly assigned into two protocols in terms of touching and injection. The injection protocol was included of five groups: Sham, control, 25, 50, and 100 ppm. They received gold nanoparticles at 25, 50, and 100 ppm concentrations administered in form of 0.3 ml/day for the period of 14 days and that of touching protocol were received 0.2 ml/day gold nanoparticles. Blood sample of which was taken to measure the serum level of creatine kinase phosphate, fasting blood, creatinine, albumin, blood urea nitrogen and eventually, the kidney was dissected for the intent of pathological analysis. Results: The serum level of creatine kinase phosphate and fasting blood sugar at middle dose was significantly different (P ≤ 0.05) in touching protocol. In both protocols, the serum level of creatinine in high and medium doses showed a significant difference (P < 0.05) associated with the treated group. In the touching method, in high and medium doses administered to the treated group, the alteration was significant (P ≤ 0.05). In the both protocols, the serum level of albumin in high and medium doses of the treated group showed significant difference (P < 0.05). Thus, the gold nanoparticles could result in undesirable effects upon kidney tissue. Conclusion: The result of this study indicated that the administration of gold nanoparticles by touching method was more effective on the serum levels of these factors than that of injection method. PMID:25878992

  1. [Toxicodynamic properties of liquids used for cooling high-power turbines. I. Acute, subacute and chronic toxicity].

    PubMed

    Seńczuk, W; Florek, E

    1983-01-01

    Oils IWiOL-3 and OMTI are used to cool the high-power turbines. Their toxicodynamic properties are little known, therefore the studies described herein have been undertaken. The studies did not reveal high acute toxicity, as A-DL50 was found to exceed 15 g/kg of body weight. The simultaneous measurements of cholinesterase activity demonstrated its clear decrease, The studies of subacute toxicity after Lim showed that OMTI after a year's exploitation is the most toxic fluid, as C-LD50 for this compound is 6,21 g/kg of body weight, whereas C-LD50 for the other oils is: 22.449 g/kg of body weight for IW i 02-3-n and 20.93 g/kg of body weight for IWiOL-3-e. Studies of chronic toxicity showed decreased cholinesterase activity and no significant changes in the measurements of certain biochemical and haematological. indices. PMID:6645933

  2. Fenugreek seeds, a hepatoprotector forage crop against chronic AlCl3 toxicity

    PubMed Central

    2013-01-01

    Background Having considered how bioavailable aluminium (Al) may affect ecological systems and animals living there, especially cattle, and in search for a preventive dietary treatment against Al toxicity, we aimed to test the protective role of fenugreek seeds against chronic liver injury induced by aluminum chloride (AlCl3) in Wistar rats. Results Five months of AlCl3 oral exposure (500 mg/kg bw i.g for one month then 1600 ppm via drinking water) caused liver atrophy, an inhibition of aspartate transaminase (AST), alanine transaminase (ALT) and glutamyl transpeptidase (GGT), an enhancement of both lipid peroxidation and lactate dehydrogenase (LDH) activity and an increase of total protein level in liver. Moreover, histopathological and histochemical examinations revealed moderate alterations in the hepatic parenchyma in addition to a disrupted iron metabolism. Co-administration of fenugreek seed powder (FSP) at 5% in pellet diet during two months succeeded to antagonize the harmful effects of AlCl3 by restoring all tested parameters. Conclusion This study highlighted the hepatotoxicity of AlCl3 through biochemical and histological parameters in one hand and the hepatoprotective role of fenugreek seeds on the other hand. Thus this work could be a pilot study which will encourage farmers to use fenugreek seeds as a detoxifying diet supplement for domestic animals. PMID:23363543

  3. Effects of bifenthrin on Daphnia magna during chronic toxicity test and the recovery test.

    PubMed

    Ye, Wei-Hong; Wen, Yue-Zhong; Liu, Wei-Ping; Wang, Zhong-Qiang

    2004-01-01

    The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied. The results showed that 24 h-EC50, 48 h-LC50 and 96 h-LC50 of bifenthrin on D. magna were 3.24, 12.40 and 1.40 microg/L respectively. And the LOEC and NOEC of bifenthrin were 0.02 and 0.004 microg/L respectively. The recovery test of bifenthrin on Daphnia magna was presented. Daphnia magna (F0 generation) were exposed during 21 d to different bifenthrin concentrations. Offspring (animals from the first and third brood: F1 (1st) and F1 (3rd), respectively) were transferred to a free pesticide medium during a 21 d recovery period. In this recovery study, survival, growth, reproduction (mean total young per female, onset of reproduction and number broods per female) and the intrinsic rate of natural increase (r) were assessed as parameters. Reproduction such as number of young per female as well as length was still reduced in F1 (1st) generation daphnids from parentals (F0) exposed to the bifenthrin. However F, (3rd) individuals from parentals exposed to pesticide concentrations were able to restore reproduction when a recovery period of 21 d was allowed, but the length of F, (3rd) from parentals exposed to the 0.5 and 0.75 microg/L bifenthrin concentration was still significantly effected (P < 0.05). PMID:15559825

  4. LAKE MICHIGAN URBAN AIR TOXICS STUDY

    EPA Science Inventory

    During the summer of 1991, an air toxics monitoring program wa conducted in the lower Lake Michigan area. his study was designed to take advantage of the intensive meteorological and oxidant data base being generated concurrently by the Lake Michigan Ozone Study (LMOS stations). ...

  5. Toxicity and recovery studies of two ayurvedic preparations of iron.

    PubMed

    Sarkar, P K; Prajapati, P K; Shukla, V J; Ravishankar, B; Choudhary, A K

    2009-12-01

    Lauha Bhasma and Mandura Bhasma in 55 mg/kg dose (5 times the therapeutic effective dose) for 60 days exhibited no serious toxic effects in Charles Foster albino rats. Both the drugs showed significant recovery from chronic toxic effect after 45 days of recovery period. PMID:20329703

  6. The chronic toxicity of CuO nanoparticles and copper salt to Daphnia magna.

    PubMed

    Adam, Nathalie; Vakurov, Alexander; Knapen, Dries; Blust, Ronny

    2015-01-01

    In this study, the effects of CuO nanoparticles and CuCl2·2H2O were tested on Daphnia magna under chronic exposure scenarios. During a 21-day exposure to the nanoparticles and salt, the reproduction was followed by a daily count of the number of offspring. After the exposure, the adult Daphnia length and uptake of copper was measured. The dissolved, nanoparticle and aggregated fractions were distinguished in the exposure medium. The results showed that only a small fraction of the nanoparticles dissolved, while the majority of the particles formed large aggregates (>450 nm). The dissolved fraction of the nanoparticles corresponded with the dissolved fraction of the copper salt. The effects of the nanoparticles (reproduction EC10: 0.546 mg Cu/l, EC20: 0.693 mg Cu/l, EC50: 1.041 mg Cu/l) on reproduction and length were much lower than the effects of the copper salts (reproduction EC10: 0.017 mg Cu/l, EC20: 0.019 mg Cu/l, EC50: 0.022 mg Cu/l). Based upon total body analysis, the Daphnia copper concentration appeared much higher when exposed to the nanoparticles than when exposed to the salt. These combined results indicate that the toxicity of CuO nanoparticles to D. magna is caused by copper ions formed during dissolution of the nanoparticles in the exposure medium. PMID:25464278

  7. Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database

    EPA Science Inventory

    Multigeneration reproduction studies are used to characterize parental and offspring systemic toxicity, as well as reproductive toxicity of pesticides, industrial chemicals and pharmaceuticals. Results from 329 multigeneration studies on 316 chemicals have been digitized into sta...

  8. A biology-based dynamic approach for the reconciliation of acute and chronic toxicity tests: application to Daphnia magna.

    PubMed

    Zaldívar, José-Manuel; Baraibar, Joaquín

    2011-03-01

    There is the need to integrate existing toxicity data in a coherent framework for extending their domain of applicability as well as their extrapolation potential. This integration would also reduce time and cost-consuming aspects of these tests and reduce animal usage. In this work, based on data extracted from literature, we have assessed the advantages that a dynamic biology-toxicant fate coupled model for Daphnia magna could provide when assessing toxicity data, in particular, the possibility to obtain from short-term (acute) toxicity test long-term (chronic) toxicity values taking into account the inherent variability of D. magna populations and the multiple sources of data. The results show that this approach overcomes some of the limitations of existing toxicity tests and that the prediction errors are considerably reduced when compared with the factor from 2 to 5 obtained using acute-to-chronic ratios. PMID:21168184

  9. TOXICITY AND METABOLISM STUDIES WITH EPA (ENVIRONMENTAL PROTECTION AGENCY) PRIORITY POLLUTANTS AND RELATED CHEMICALS IN FRESHWATER ORGANISMS

    EPA Science Inventory

    Twenty-two chemicals from the EPA priority pollutant list were studied for their acute and/or chronic toxicity to selected freshwater organisms. Freshwater species tested included the fathead minnow (Pimephales promelas), rainbow trout (Salmo gairdneri), bluegill sunfish (Lepomis...

  10. Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro

    SciTech Connect

    McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A. . E-mail: j.heffron@ucc.ie

    2007-02-15

    Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography. A neuroblastoma cell line (SH-SY5Y) was exposed to toluene for the same period. Following exposure, cells were harvested and toxicity measured in terms of the following endpoints: membrane damage (LDH leakage), perturbations in intracellular free Ca{sup 2+}, changes in glutathione redox status and dual-phosphorylation of MAP kinases ERK1/2, JNK and p38. The results show that sub-chronic exposure to the volatile organic solvents causes membrane damage, increased intracellular free calcium and altered glutathione redox status in both cell lines. However, acute and sub-chronic solvent exposure did not result in MAP kinase phosphorylation. Toxicity of the solvents tested increased with hydrophobicity. The lowest-observed-adverse-effect-levels (LOAELs) measured in vitro were close to blood solvent concentrations reported for individuals exposed to the agents at levels at or below their individual threshold limit values (TLVs)

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

    PubMed

    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. PMID:22887798

  12. Anomalies on capture nets of Hydropsyche slossonae larvae (Trichoptera; Hydropsychidae), a potential indicator of chronic toxicity of malathion (organophosphate insecticide).

    PubMed

    Tessier; Boisvert; Vought; Lacoursière

    2000-08-01

    A laboratory study on the sublethal effects of malathion on the net-spinning behavior of the caddisfly larvae Hydropsyche slossonae was conducted in order to assess the potential of net anomalies as an indicator of chronic exposure to organophosphorus insecticides. Two anomalies were identified after chronic exposure to 0.01, 0.05, 0.1, 0.5 and 1.0 µg l(-1) malathion. The first was a distortion of the midline meshes where the normal diamond shape structure was disrupted and the meshes were separated by extra strands (called 'midline' anomaly). The second aberration observed was a significant decrease in net symmetry. Both anomalies were highly correlated to the toxic action of malathion, i.e. inhibition of the acetylcholinesterase enzyme (AChE). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses of capture nets did not show any modification of silk polypeptides after exposure to malathion, indicating that net distortions were not related to silk composition. Both anomalies seem to represent the symptoms of the specific toxic action of malathion; nevertheless, they can serve as an index of the physiological condition of the larvae, especially the midline anomaly. The symmetry of the nets decreased significantly after exposure to 0.5 and 1.0 µg l(-1). However, the toxicity curves (EC(50)) showed that the sensitivity threshold for the midline anomaly ranged from 0.11 to 0.28 µg l(-1), which reflect more realistic exposure to concentrations expected to occur in the field. Hence, the use of capture net anomalies of hydropsychid larvae could represent a valuable indicator of sublethal toxicity induced by malathion and other organophosphorus insecticides in running waters. PMID:10930655

  13. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. PMID:25456049

  14. Acute toxic effects of sustained-release verapamil in chronic renal failure.

    PubMed

    Pritza, D R; Bierman, M H; Hammeke, M D

    1991-10-01

    Four hypertensive patients with chronic renal insufficiency or end-stage renal disease who were treated with sustained-release verapamil hydrochloride subsequently developed acute toxic effects. All four patients developed varying degrees of atrioventricular heart block, hypotension, hyperkalemia, metabolic acidosis, and hepatic dysfunction. Supportive treatment consisted of intravenous catecholamines, sodium polystyrene sulfonate, and dialysis, and all patients recovered completely without any residual hepatic or cardiac disease. Patients with renal impairment who are treated with sustained-release verapamil may accumulate verapamil or its metabolites and develop toxic side effects. We conclude that sustained-release verapamil should be used with caution in this patient population and that patients should be closely monitored for adverse cardiovascular, metabolic, and hepatic side effects. PMID:1843183

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

    PubMed

    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. PMID:22940740

  16. Species sensitivity distribution evaluation for chronic nickel toxicity to marine organisms.

    PubMed

    DeForest, David K; Schlekat, Christian E

    2013-10-01

    In Europe, the European Union's Existing Substances Regulation (EEC 793/93), the REACH Regulation, and Water Framework Directive all share common guidance for conducting environmental effects assessments, which can be further used to derive predicted no effect concentrations (PNECs) and environmental quality standards (EQS) for chemical substances. To meet the criteria for using a species sensitivity distribution (SSD) in the effects assessment of Ni for marine organisms, chronic toxicity data from the published scientific literature were augmented with toxicity testing of several additional marine species including: a unicellular alga (Dunalliela tertiolecta), a diatom (Skeletonema costatum), 2 macroalgae (Champia parvula, Macrocystis pyrifera), 2 mollusks (Crassostrea gigas, Mytilus galloprovincialis), 2 echinoderms (Dendraster excentricus, Strongylocentrotus purpuratus), a polychaete (Neanthes arenaceodentata), and a fish (Cyprinodon variegatus). Based on this updated database, which includes chronic Ni toxicity data for a total of 17 marine species, HC5 values (hazardous concentrations to 5% of the species) were derived using an SSD. The most sensitive species is a tropical sea urchin from the Caribbean region, Diadema antillarum, which has an EC10 that is approximately 6-fold less than the EC10 for the second most sensitive species tested. There is some uncertainty in the representativeness of D. antillarum to temperate European marine waters because 1) a European sea urchin species (Paracentrotus lividus) is approximately 48-fold less sensitive to Ni, and (2) ambient marine Ni concentrations in at least some European waters closely approach the D. antillarum EC10. The HC5 values with and without D. antillarum included in the SSD are 3.9 and 20.9 μg/L, respectively. Site-specific toxicity testing with local species may be warranted for locations where Ni concentrations fall between the range in HC5s of 3.9 to 20.9 μg/L. PMID:23553986

  17. Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

    PubMed

    Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

    2002-02-01

    The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture. PMID:11911491

  18. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.

    PubMed

    Terasaki, Masanori; Abe, Ryoko; Makino, Masakazu; Tatarazako, Norihisa

    2015-01-01

    The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg L(-1) , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L(-1) and from 1.2 to 19 mg L(-1) , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L(-1) for MP, BnP, and Cl2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0

  19. Chronic cadmium exposure: relation to male reproductive toxicity and subsequent fetal outcome

    SciTech Connect

    Zenick, H.; Hastings, L.; Goldsmith, M.; Niewenhuis, R.J.

    1982-03-01

    Acute injections of high doses of Cd induced marked testicular necrosis. However, the effects of low-dose, oral Cd exposure on a chronic basis are not well documented. The present investigation was designed to examine the effects of such exposure as reflected in parameters of spermatotoxicity and histology. Moreover, the impact on fetal outcome was measured by evaluating teratological and postnatal neurobehavior endpoints. Male Long-Evans hooded rats (100 d of age) were exposed to 0, 17.2, 34.4, or 68.8 ppm Cd for 70 d. During this period, the animals were maintained on a semipurified diet to control for the contribution of Zn and other trace elements. Near the end of exposure the males were mated to three female rats. One was sacrificed on d 21 of pregnancy for teratological assessment, including fetal weight, and determination of preimplantation and postimplantation loss. The other two dams were allowed to deliver, and their offspring were tested on tasks of exploratory behavior (d 21) and learning (d 90). Subsequently, the male parent was sacrified and a variety of measures recorded including weights of testes and caudae epididymides, sperm count and sperm morphology, and Cd content of liver and kidney. One of the testes was also evaluated histologically. No significant effects were observed on any of the parameters of reproductive toxicity or fetal outcome. These findings suggest that, at the doses employed in this study, Cd did not have signficant deleterious effects on the male reproductive system. Morever, the traditional view of Cd-related testicular insult, based on acute exposure, injection protocols, needs to be reevaluated in terms of environmental relevance.

  20. Chronic toxicity and oncogenicity of decamethylcyclopentasiloxane in the Fischer 344 Rat.

    PubMed

    Jean, Paul A; Plotzke, Kathleen P; Scialli, Anthony R

    2016-02-01

    Decamethylcyclopentasiloxane (D5) is a cyclic polydimethylsiloxane used in the synthesis of silicon-based materials and as a component in consumer products. Male and female Fischer 344 rats were exposed to D5 vapor (0, 10, 40, 160 ppm; whole-body inhalation) for 6 h/d, 5 d/wk, for up to 104 weeks. Microscopic examination of tissues revealed test article effects at 160 ppm in the upper respiratory tract (hyaline inclusions in males and females at 6, 12, and 24 months) and an increased incidence of uterine endometrial adenocarcinoma at 24-months. The hyaline inclusions were considered a non-adverse tissue response for lack of any other respiratory tract non-neoplastic or neoplastic changes. Uterine endometrial adenocarcinoma was not anticipated. Toxicity testing (mutagenicity/genotoxicity, acute, sub-acute and sub-chronic descriptive toxicity) performed prior to the conduct of the chronic bioassay provided no indication that the uterus was a potential target organ. The target organ and tumor type specificity (adenocarcinoma is a common spontaneous tumor in the aged Fischer 344 rat) suggests the effect is associated with estrous cycle alteration. A robust assessment of potential mode(s) of action responsible for the uterine tumors and relevance to humans is addressed in a companion manuscript (Klaunig et al., 2015). PMID:26184430

  1. Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine☆

    PubMed Central

    Nevin, Remington L.

    2014-01-01

    Mefloquine is a quinoline derivative antimalarial which demonstrates promise for the treatment of schistosomiasis. Traditionally employed in prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria, recent changes to the approved European and U.S. product labeling for mefloquine now warn of a risk of permanent and irreversible neurological sequelae including vertigo, loss of balance and symptoms of polyneuropathy. The newly described permanent nature of certain of these neurological effects challenges the conventional belief that they are due merely to the long half-life of mefloquine and its continued presence in the body, and raises new considerations for the rational use of the drug against parasitic disease. In this opinion, it is proposed that many of the reported lasting adverse neurological effects of mefloquine are consistent with the chronic sequelae of a well characterized but idiosyncratic central nervous system (CNS) toxicity syndrome (or toxidrome) common to certain historical antimalarial and antiparasitic quinolines and associated with a risk of permanent neuronal degeneration within specific CNS regions including the brainstem. Issues in the development and licensing of mefloquine are then considered in the context of historical awareness of the idiosyncratic CNS toxicity of related quinoline drugs. It is anticipated that the information presented in this opinion will aid in the future clinical recognition of the mefloquine toxidrome and its chronic sequelae, and in informing improved regulatory evaluation of mefloquine and related quinoline drugs as they are explored for expanded antiparasitic use and for other indications. PMID:25057461

  2. Escin, a novel triterpene, mitigates chronic MPTP/p-induced dopaminergic toxicity by attenuating mitochondrial dysfunction, oxidative stress, and apoptosis.

    PubMed

    Selvakumar, Govindasamy Pushpavathi; Manivasagam, Thamilarasan; Rekha, Karamkolly R; Jayaraj, Richard L; Elangovan, Namasivayam

    2015-01-01

    Parkinson's disease (PD) is a common, chronic, and debilitating neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons due to unknown factors. In the present study, we have evaluated if escin, a triterpene saponin from seeds of horse chestnut tree (Aesculus hippocastanum), offers neuroprotection against chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced toxicity using a mouse model. Chronic administration of MPTP/p deteriorated the loss of TH immunoreactivity in striatum. Subsequently, MPTP/p also enhanced oxidative stress by mitochondrial complex I inhibition, thereby ensuing dopaminergic denervation via modulation of Bcl-2, Bax, Cyto-C, and cleaved caspases expressions. However, we observed that pretreatment with escin (4 mg/kg) significantly attenuated MPTP/p-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, behavioral studies and ultrastructural analysis of mitochondria and intracellular components were in support of these findings. Therefore, we speculate that escin might be a promising candidate for the prevention of mitochondrial dysfunction-induced apoptosis in neurodegenerative disorders such as PD. PMID:24788336

  3. Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

    PubMed

    Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

    1999-12-01

    The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

  4. Acute and chronic toxicity of endosulfan to crab: Effect on lipid metabolism

    SciTech Connect

    Rafi, G.Md.; Srinivas, T.; Reddy, S.J.; Reddy, D.C.; Ramamurthi, R. )

    1991-12-01

    Endosulfan is toxic to fish and its toxic effects have been studied in several freshwater fish. However, information regarding toxicity of endosulfan to many freshwater invertebrates is fragmentary. Few reports are available on the toxic effect of endosulfan on carbohydrate and protein metabolisms of freshwater field crab, Oziotelphusa senex senex, another nontarget organism of aquatic ecosystem. The work on lipid metabolism under organochloride insecticide (OCI) stress is scant. The OCI tend to accumulate in the lipid rich tissues of the biosystem due to their lipophilic nature. The changes in lipid profiles under OCI stress reported to cause profound changes in the metabolism and physiology of animals. Therefore, this paper presents the effects of endosulfan on lipid metabolism in O. senex senex.

  5. Chronic toxicity of chloride to freshwater species: effects of hardness and implications for water quality guidelines.

    PubMed

    Elphick, James R F; Bergh, Kelli D; Bailey, Howard C

    2011-01-01

    Toxicity tests using nine freshwater species (Ceriodaphnia dubia, Daphnia magna, Oncorhynchus mykiss, Pimephales promelas, Lumbriculus variegatus, Tubifex tubifex, Chironomus dilutus, Hyallela azteca, and Brachionus calyciflorus) were conducted to evaluate their sensitivity to chloride. Acute-to-chronic ratios (ACRs) from these tests indicate the ACR of 7.59 employed by the United States Environmental Protection Agency (U.S. EPA) in deriving its water quality guideline for chloride may be conservative; a revised ACR of 3.50 is presented here. The endpoints used to calculate the ACR included 24-h to 96-h median lethal concentrations (LC50s) for acute tests, and 48-h to 54-d inhibition concentration (ICx) values for growth or reproduction for chronic exposures. Data from the present chronic toxicity tests, and other investigators, were used to propose a water quality guideline for long-term exposure to chloride using a species sensitivity distribution (SSD) approach. The 5th percentile from the SSD was calculated as 307 mg/L and proposed as the water quality guideline. Cladocerans were the most sensitive species in the dataset. Ceriodaphnia dubia was used to evaluate the relationship between water hardness and sensitivity to chloride. A strong relationship was observed and was used to establish a hardness-related equation to modify the proposed water quality guideline on the basis of water hardness, resulting in values ranging from 64 mg/L chloride at 10 mg/L hardness to 388 mg/L chloride at 160 mg/L hardness (as CaCO₃). These data suggest that current water quality guidelines for chloride may be overly conservative in water with moderate-to-high hardness, and may not be sufficiently protective under soft-water conditions. PMID:20872898

  6. Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca

    USGS Publications Warehouse

    Besser, John M.; Ivey, Chris D.; Brumbaugh, William G.; Ingersoll, Christopher G.

    2016-01-01

    The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeastþcereal leafþtrout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatomsþTetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20]¼13 mg/L and 15mg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 mg/L, but these endpoints were significantly reduced by Pb in the YCT test—and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model–normalized effect concentrations for the 3 tests ranged from 3.7mg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 mg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes.

  7. Effect of diet quality on chronic toxicity of aqueous lead to the amphipod Hyalella azteca.

    PubMed

    Besser, John M; Ivey, Chris D; Brumbaugh, William G; Ingersoll, Christopher G

    2016-07-01

    The authors investigated the chronic toxicity of aqueous Pb to the amphipod Hyalella azteca (Hyalella) in 42-d tests using 2 different diets: 1) the yeast + cereal leaf + trout pellet (YCT) diet, fed at the uniform low ration used in standard methods for sediment toxicity tests; and 2) a new diet of diatoms + TetraMin flakes (DT), fed at increasing rations over time, that has been optimized for use in Hyalella water-only tests. Test endpoints included survival, weight, biomass, fecundity, and total young. Lethal effects of Pb were similar for the DT and YCT tests (20% lethal concentration [LC20] = 13 μg/L and 15 μg/L, respectively, as filterable Pb). In contrast, weight and fecundity endpoints were not significantly affected in the DT test at Pb concentrations up to 63 µg/L, but these endpoints were significantly reduced by Pb in the YCT test-and in a 2005 test in the same laboratory with a diet of conditioned Rabbit Chow (RC-2005). The fecundity and total young endpoints from the YCT and RC-2005 tests were considered unreliable because fecundity in controls did not meet test acceptability criteria, but both of these tests still produced lower Pb effect concentrations (for weight or biomass) than the test with the DT diet. The lowest biotic ligand model-normalized effect concentrations for the 3 tests ranged from 3.7 μg/L (weight 20% effect concentration [EC20] for the RC-2005 test) to 8.2 μg/L (total young EC20 for the DT test), values that would rank Hyalella as the second or third most sensitive of 13 genera in a species sensitivity distribution for chronic Pb toxicity. These results demonstrate that toxicity tests with Hyalella fed optimal diets can meet more stringent test acceptability criteria for control performance, but suggest that results of these tests may underestimate sublethal toxic effects of Pb to Hyalella under suboptimal feeding regimes. Environ Toxicol Chem 2016;35:1825-1834. Published 2015 Wiley Periodicals Inc

  8. Effect of indigenous animals on chronic end points in freshwater sediment toxicity tests

    SciTech Connect

    Reynoldson, T.B.; Day, K.E.; Clarke, C.; Milani, D. )

    1994-06-01

    Sediment toxicity tests were conducted using three species of benthic invertebrates, Chironomus riparius, Hyalella azteca, and Hexagenia limbata, with various densities of the oligochaete worm Tubifex tubifex. It was shown that indigenous animals, simulated by the presence of Tubifex tubifex, did not affect survival of the test species (P [>=] 0.05) but did reduce growth in all three test species and in two species at the lowest tested densities, equivalent to 1,460 worms per square meter. At densities of Tubifex tubifex equivalent to 20,000 m[sup [minus]2], the growth of Chironomus riparius was reduced by >90%, Hyalella azteca by >60%, and Hexagenia limbata by almost 50%. The densities of oligochaetes are equivalent to those found in many contaminated sites. Therefore, it is concluded that the presence of indigenous organisms can confound the interpretation of toxicity test results, based on chronic end points. It is recommended that removal of organisms by considered before toxicity tests are conducted with freshwater sediments from sites with large populations of benthic invertebrates, especially oligochaete worms.

  9. A k-NN algorithm for predicting the oral sub-chronic toxicity in the rat.

    PubMed

    Gadaleta, Domenico; Pizzo, Fabiola; Lombardo, Anna; Carotti, Angelo; Escher, Sylvia E; Nicolotti, Orazio; Benfenati, Emilio

    2014-01-01

    Repeated dose toxicity is of the utmost importance to characterize the toxicological profile of a chemical after repeated administration. Its evaluation refers to the Lowest-Observed-(Adverse)-Effect-Level (LO(A)EL) explicitly requested in several regulatory contexts, such as REACH and EC Regulation 1223/2009 on cosmetic products. So far in vivo tests have been the sole viable option to assess repeated dose toxicity. We report a customized k-Nearest Neighbors approach for predicting sub-chronic oral toxicity in rats. A training set of 254 chemicals was used to derive models whose robustness was challenged through leave-one-out cross-validation. Their predictive power was evaluated on an external dataset comprising 179 chemicals. Despite the intrinsically heterogeneous nature of the data, our models give promising results, with q²≥0.632 and external r²≥0.543. The confidence in prediction was ensured by implementing restrictive user-adjustable rules excluding suspicious chemicals irrespective of the goodness in their prediction. Comparison with the very few LO(A)EL predictive models in the literature indicates that the results of the present analysis can be valuable in prioritizing the safety assessment of chemicals and thus making safe decisions and justifying waiving animal tests according to current regulations concerning chemical safety. PMID:25048736

  10. Acute and Chronic Toxicity of Nitrate to Early Life Stages of Zebrafish--Setting Nitrate Safety Levels for Zebrafish Rearing.

    PubMed

    Learmonth, Cândida; Carvalho, António Paulo

    2015-08-01

    Recirculating aquaculture systems (RAS) have been widely used for zebrafish rearing, allowing holding of many thousands of fish at high densities. Water quality in RAS largely depends on biofilters that ultimately convert the extremely toxic ammonia excreted by fish into the much less toxic nitrate. However, when water renewal is minimal in RAS, nitrate can accumulate to high enough levels to negatively impact fish welfare and performance. Therefore, the setting of safety levels of nitrate for zebrafish should be a priority to avoid unwanted effects in both the intensive production of this species and research outputs. The present study aimed to define nitrate safety levels for zebrafish based on acute and chronic toxicity bioassays in early life stages of this species. Acute bioassays revealed ontogenetic changes in response to high nitrate levels. Based on NOEC (no observed effect concentration) values, safety levels should be set at 1450, 1855, and 1075 mg/L NO3(-)-N to prevent acute lethal effects in embryos, newly-hatched larvae, and swim-up larvae, respectively. In the chronic bioassay, larvae were exposed to nitrate concentrations of 50, 100, 200, and 400 mg/L NO3(-)-N during the entire larval period (23 days). No negative effects were observed either on larval performance or condition at concentrations up to 200 mg/L NO3(-)-N. However, at 400 mg/L NO3(-)-N, survival drastically decreased and fish showed reduced growth and evidence of morphological abnormalities. Accordingly, a safety level of 200 mg/L NO3(-)-N is recommended during the larval rearing of zebrafish to prevent negative impacts on juvenile production. PMID:25996778

  11. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

    PubMed Central

    Kalsi, Sarbjeet S.; Wood, David M.; Dargan, Paul I.

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  12. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use.

    PubMed

    Kalsi, Sarbjeet S; Wood, David M; Dargan, Paul I

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  13. Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

    PubMed

    Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

    2016-08-01

    The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic

  14. TOXICANT IDENTIFICATION STUDIES ON A HARBOR SEDIMENT

    EPA Science Inventory

    Presentation summarizes the results of experiments on sediment toxicity identification evaluation (TIE) techniques that allow researchers to characterize and identify chemical causes of acute toxicity in sediments that can be applied using the 10-d solid-phase sediment toxicity t...

  15. Assessment of chronic toxicity and carcinogenicity in rats of Wingstay 100, a rubber antioxidant/antiozonant.

    PubMed

    Iatropoulos, M J; Williams, G M; Wang, C X; Brunnemann, K D; Leber, A P

    1997-08-01

    The chronic toxicity and carcinogenicity of Wingstay 100 (W 100), a rubber antioxidant/antiozonant, were studied in Fischer 344 (F 344) rats in two chronic studies. Earlier genetic studies indicated that the product had weak activity in a bacterial mutation assay, but lacked activity in chromosomal aberration assays. In an one year study, both genders of F 344 rats were exposed to 53, 310 or 1900 ppm in NIH-07 diet for 52 weeks, and sacrifices were made at 38, 52 and 64 weeks. No test substance related deaths occurred, although the high dose of 1900 ppm caused a decrease in body weight gain and food consumption in both genders. Red blood cell mean corpuscular volume was significantly increased at 38 weeks, accompanied by a significant decrease in mean corpuscular hemoglobin concentration. At 52 weeks, the red blood cell count and hemoglobin values were also significantly decreased in high dose animals of both genders. Total bilirubin and cholesterol were increased in high dose animals of 38 and 52-week sacrifices. During the 3 month recovery, hematology parameters, bilirubin and cholesterol returned to control values. Total protein was reduced in high dose animals of both genders, throughout the entire exposure and recovery periods. W 100 also produced increases in relative liver, spleen, heart and kidney weights in high dose animals. Both genders of all W 100 groups exhibited significant increases in urothelial cell proliferation (measured by PCNA) and adaptive hyperplasia. No regenerative hyperplasia, preneoplasia, or neoplasia were present. There was microscopic evidence of extramedullary erythropoiesis in the spleen and liver of high dose animals in both genders, otherwise no other pertinent microscopic finding was evident. In parallel, an accelerated bioassay (ABA) was conducted, which is a mechanistic initiation/promotion carcinogenicity study designed to assess tumor induction and promotion potential of a test substance in major organs of carcinogenesis. The

  16. Standardization of a chronic sediment toxicity test with Chironomus riparius -- An EU collaboration

    SciTech Connect

    Fleming, R.; Grootelaar, L.; Guchte, C. van de |

    1995-12-31

    Because of the need for sensitive measures of low level contaminants in European sediments, a chronic sediment toxicity test method, using Chironomus riparius has been developed as part of a collaborative program for the European Commission. The protocol is a partial life cycle test exposing the animals from egg stage to pre-emergence in sediment-water systems. In 1995 the protocol was ring tested in several laboratories in Europe, the US and Canada using the moth-proofer permethrin as a model substance. This was spiked into a natural sediment using a spiking protocol also developed in this program. Results of the ring test and details of the protocols will be presented.

  17. Comparison of the capacity of two biotic ligand models to predict chronic copper toxicity to two Daphnia magna clones and formulation of a generalized bioavailability model.

    PubMed

    Van Regenmortel, Tina; Janssen, Colin R; De Schamphelaere, Karel A C

    2015-07-01

    Although it is increasingly recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the use of 2 differently structured and parameterized BLMs (1 in the United States and another in the European Union) to obtain bioavailability-based chronic water quality criteria for copper is worthy of further investigation. In the present study, the authors evaluated the predictive capacity of these 2 BLMs for a large dataset of chronic copper toxicity data with 2 Daphnia magna clones, termed K6 and ARO. One BLM performed best with clone K6 data, whereas the other performed best with clone ARO data. In addition, there was an important difference between the 2 BLMs in how they predicted the bioavailability of copper as a function of pH. These modeling results suggested that the effect of pH on chronic copper toxicity is different between the 2 clones considered, which was confirmed with additional chronic toxicity experiments. Finally, because fundamental differences in model structure between the 2 BLMs made it impossible to create an average BLM, a generalized bioavailability model (gBAM) was developed. Of the 3 gBAMs developed, the authors recommend the use of model gBAM-C(uni), which combines a log-linear relation between the 21-d median effective concentration (expressed as free Cu(2+) ion activity) and pH, with more conventional BLM-type competition constants for sodium, calcium, and magnesium. This model can be considered a first step in further improving the accuracy of chronic toxicity predictions of copper as a function of water chemistry (for a variety of Daphnia magna clones), even beyond the robustness of the current BLMs used in regulatory applications. PMID:25771778

  18. Evaluation of sub-chronic toxic effects of petroleum ether, a laboratory solvent in Sprague-Dawley rats

    PubMed Central

    Parasuraman, Subramani; Sujithra, Jeyabalan; Syamittra, Balakrishnan; Yeng, Wong Yeng; Ping, Wu Yet; Muralidharan, Selvadurai; Raj, Palanimuthu Vasanth; Dhanaraj, Sokkalingam Arumugam

    2014-01-01

    Background: In general, organic solvents are inhibiting many physiological enzymes and alter the behavioural functions, but the available scientific knowledge on laboratory solvent induced organ specific toxins are very limited. Hence, the present study was planned to determine the sub-chronic toxic effects of petroleum ether (boiling point 40–60°C), a laboratory solvent in Sprague-Dawley (SD) rats. Materials and Methods: The SD rats were divided into three different groups viz., control, low exposure petroleum ether (250 mg/kg; i.p.) and high exposure petroleum ether (500 mg/kg; i.p.) administered group. The animals were exposed with petroleum ether once daily for 2 weeks. Prior to the experiment and end of the experiment animals behaviour, locomotor and memory levels were monitored. Before initiating the study animals were trained for 2 weeks for its learning process and its memory levels were evaluated. Body weight (BW) analysis, locomotor activity, anxiogenic effect (elevated plus maze) and learning and memory (Morris water navigation task) were monitored at regular intervals. On 14th day of the experiment, few ml of blood sample was collected from all the experimental animals for estimation of biochemical parameters. At the end of the experiment, all the animals were sacrificed, and brain, liver, heart, and kidney were collected for biochemical and histopathological analysis. Results: In rats, petroleum ether significantly altered the behavioural functions; reduced the locomotor activity, grip strength, learning and memory process; inhibited the regular body weight growth and caused anxiogenic effects. Dose-dependent organ specific toxicity with petroleum ether treated group was observed in brain, heart, lung, liver, and kidney. Extrapyramidal effects that include piloerection and cannibalism were also observed with petroleum ether administered group. These results suggested that the petroleum ether showed a significant decrease in central nervous system

  19. Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

    USGS Publications Warehouse

    Meinertz, J.R.; Schreier, T.M.; Bernardy, J.A.; Franz, J.L.

    2010-01-01

    Diphenhydramine hydrochloride (DH; Benadryl TM, an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 lg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 (mu or u)g/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 (mu or u)g/L and for ET was 248 (mu or u)g/L.

  20. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

  1. Chronic toxicity of mixtures of copper, cadmium and zinc to Daphnia pulex

    SciTech Connect

    Flickinger, A.L.

    1984-01-01

    Daphnia pulex (de Greer) were exposed to single and bimetal mixtures of copper, cadmium and zinc in reconstituted waters of different hardness/alkalinity and humic acid concentrations. The effect of single and bimetal exposure to these metals was evaluated by survivorship and reproductive indices of brood size, percent aborted eggs/brood, age at reproductive maturity, age at first reproduction and the instantaneous rate of population growth. Accumulation by 7-day-old Daphnia magna of metals in these mixtures was also assessed in medium water containing 0.0 and 0.75 mg humic acid/L. The addition of 0.75 mg humic acid/L decreased the acute toxicity of copper and zinc but increased the acute toxicity of cadmium. Survival was the best index of a single or bimetal chronic stress since it was equally or more sensitive than any reproductive index. The interaction between copper and zinc was variable in soft water which contained 0.15 mg humic acid/L, but largely independent in medium water which contained 0.0 and 0.75 mg humic acid/L. Zinc and humic acid had no effect on the accumulation of copper in medium water. Copper and cadmium were synergistic in their interaction on daphniid survival in medium water which contained 0.0 and 0.75 mg humic acid/L.

  2. Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence?

    PubMed Central

    Lewerenz, Jan; Maher, Pamela

    2015-01-01

    Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors) and a class of G-protein coupled receptors (metabotropic glutamate receptors). Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases. PMID:26733784

  3. [Biological models in studying of staphylococci enterotoxin toxicity].

    PubMed

    Shepeliakovskaia, A O; Semushina, S G; Murashev, A N; Adameĭko, I I; Brovko, F A

    2014-01-01

    Enterotoxins--superantigens--are the main toxic agents of staphylococci. Currently, an important role of these proteins is estabished in both toxicity itself--toxic shock and in the development of autoimmune diseases. Enterotoxin studies are carried out in several directions including the search for novel molecular targets, studies in cell tests and establishment of toxicity in animal models. Methods of studying toxicity in animal models: monkeys, mice and rabbits are examined in the review. Methods of animal priming to achieve lethality, features of using various lines of mice during analysis of individual enterotoxins are discussed. Methods of studying enterotoxin-neutralizing compounds in animal models are discussed. PMID:25536781

  4. Lethal and sublethal measures of chronic copper toxicity in the eastern narrowmouth toad, Gastrophryne carolinensis.

    PubMed

    Flynn, R Wesley; Scott, David E; Kuhne, Wendy; Soteropoulos, Diana; Lance, Stacey L

    2015-03-01

    Many metals are acutely toxic to aquatic organisms at high concentrations and for some metals, such as copper (Cu), even low-level chronic contamination may be cause for conservation concern. Amphibian susceptibility to Cu has been examined in only a few species, and susceptibility is highly variable. The lethal and sublethal effects were examined of chronic aqueous Cu exposure on embryonic and larval eastern narrowmouth toads, Gastrophryne carolinensis. Copper levels as low as 10 μg Cu/L reduced embryonic and larval survival. Embryonic survivorship varied within- and between-source populations, with embryos derived from uncontaminated-wetland parents having greater survival at lower Cu levels than embryos from parents from a metal-contaminated constructed wetland. At 30 μg/L, embryos from the contaminated site had greater survival. Overall survival from oviposition to metamorphosis was 68.9% at 0 μg/L and 5.4% at 10 μg/L. Similarly, embryos exposed to ≥50 μg/L demonstrated developmental delays in transition from embryo to free-swimming larva. These results demonstrate a negative population-specific response to environmentally relevant levels of Cu. PMID:25475581

  5. The chronic toxicity of molybdate to marine organisms. I. Generating reliable effects data.

    PubMed

    Heijerick, D G; Regoli, L; Stubblefield, W

    2012-07-15

    A scientific research program was initiated by the International Molybdenum Association (IMOA) which addressed identified gaps in the environmental toxicity data for the molybdate ion (MoO(4)(2-)). These gaps were previously identified during the preparation of EU-REACH-dossiers for different molybdenum compounds (European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances; EC, 2006). Evaluation of the open literature identified few reliable marine ecotoxicological data that could be used for deriving a Predicted No-Effect Concentration (PNEC) for the marine environment. Rather than calculating a PNEC(marine) using the assessment factor methodology on a combined freshwater/marine dataset, IMOA decided to generate sufficient reliable marine chronic data to permit derivation of a PNEC by means of the more scientifically robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Nine test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na(2)MoO(4)·2H(2)O) according to published standard testing guidelines that are acceptable for a broad range of regulatory purposes. The selected test organisms were representative for typical marine trophic levels: micro-algae/diatom (Phaeodactylum tricornutum, Dunaliella tertiolecta), macro-alga (Ceramium tenuicorne), mysids (Americamysis bahia), copepod (Acartia tonsa), fish (Cyprinodon variegatus), echinoderms (Dendraster exentricus, Strongylocentrotus purpuratus) and molluscs (Mytilus edulis, Crassostrea gigas). Available NOEC/EC(10) levels ranged between 4.4 mg Mo/L (blue mussel M. edulis) and 1174 mg Mo/L (oyster C. gigas). Using all available reliable marine chronic effects data that are currently available, a HC(5,50%) (median hazardous concentration affecting 5% of the species) of 5.74(mg Mo)/L was derived with the statistical extrapolation approach, a value that can be used for national and

  6. Toxicity in relation to mode of action for the nematode Caenorhabditis elegans: Acute-to-chronic ratios and quantitative structure-activity relationships.

    PubMed

    Ristau, Kai; Akgül, Yeliz; Bartel, Anna Sophie; Fremming, Jana; Müller, Marie-Theres; Reiher, Luise; Stapela, Frederike; Splett, Jan-Paul; Spann, Nicole

    2015-10-01

    Acute-to-chronic ratios (ACRs) and quantitative structure-activity relationships (QSARs) are of particular interest in chemical risk assessment. Previous studies focusing on the relationship between the size or variation of ACRs to substance classes and QSAR models were often based on data for standard test organisms, such as daphnids and fish. In the present study, acute and chronic toxicity tests were performed with the nematode Caenorhabditis elegans for a total of 11 chemicals covering 3 substance classes (nonpolar narcotics: 1-propanol, ethanol, methanol, 2-butoxyethanol; metals: copper, cadmium, zinc; and carbamates: methomyl, oxamyl, aldicarb, dioxacarb). The ACRs were variable, especially for the carbamates and metals, although there was a trend toward small and less variable ACRs for nonpolar narcotic substances. The octanol-water partition coefficient was a good predictor for explaining acute and chronic toxicity of nonpolar narcotic substances to C. elegans, but not for carbamates. Metal toxicity could be related to the covalent index χm2r. Overall, the results support earlier results from ACR and QSAR studies with standard freshwater test animals. As such C. elegans as a representative of small soil/sediment invertebrates would probably be protected by risk assessment strategies already in use. To increase the predictive power of ACRs and QSARs, further research should be expanded to other species and compounds and should also consider the target sites and toxicokinetics of chemicals. PMID:25994998

  7. Sub-chronic Dermal Toxicity of Silver Nanoparticles in Guinea Pig: Special Emphasis to Heart, Bone and Kidney Toxicities

    PubMed Central

    Korani, Mitra; Rezayat, Seyed Mahdi; Arbabi Bidgoli, Sepideh

    2013-01-01

    Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks . A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: ki dney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure ,which has the potential to provide target organ toxicities in a time and dose dependent manner. PMID:24250657

  8. Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

    NASA Astrophysics Data System (ADS)

    Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

    2014-05-01

    Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

  9. Toxicity study of Lauha Bhasma (calcined iron) in albino rats

    PubMed Central

    Joshi, Namrata; Dash, Manoj Kumar; Dwivedi, Laxmikant; Khilnani, G. D.

    2016-01-01

    Background: Lauha Bhasma (LB) is a complex herbomineral preparation widely used as an Ayurvedic hematinic agent. It is an effective remedy for chronic fever (jīrṇa jvara), phthisis (kṣaya), Breathlessness (śvāsa) etc., and possesses vitality enhancing (vājīkara), strength promoting and anti aging (rasāyana) properties. Objectives: The present work was conducted to establish the safety aspects of the use of Lauha bhasma. Setting and Design: LB was prepared by Ayurvedic procedures of purification (śodhana), sun drying (bhānupāka), sthālīpāka, followed by repeated calcination (māraṇa) and “nectarization” (amṛtīkaraṇa). The resultant product was subjected to acute and sub acute toxicity studies. Materials and Methods: Acute and subacute toxicity study of LB was conducted in albino rats. Criteria for assessment included ponderal changes, change in biochemical parameters viz., LFT and KFT and hematological parameters. Histopathological studies of different organs including liver, kidney, spleen, testis etc., were also conducted to observe pathological changes if any. Results: In the acute toxicity study, the animal group did not manifest any signs of toxicity and no mortality was observed up to 100 times the therapeutic dose (TD). Significant increase in blood urea (27.83%, P < 0.01), serum creatinine (30.92%, P < 0.05), Aspartate aminotransferase (15.09%, P < 0.05), and serum alkaline phosphatase (27.5%, P < 0.01) was evident in group IV (10 TD). A significant increase in serum total protein (6.04%, P < 0.05) level was observed in group III (5 TD). Histopathological examination of livers in group IV (10 TD) showed mild inflammation in terms of bile stasis, peri-portal hepatic inflammation and sinusoidal congestion; lymphocyte infiltration in kidney and intracellular deposits in the splenic tissue. Conclusion: Lauha Bhasma was found to be safe at the therapeutic dose and also at five times the therapeutic dose levels. However, alteration in

  10. Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

    EPA Science Inventory

    Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

  11. Corrosion-induced Whole Effluent Toxicity from a cooling tower: A toxicity reduction evaluation case study

    SciTech Connect

    Fort, D.J.; Stover, E.L.; Talley, J.M.; Copenhaver, M.B.

    1996-11-01

    As the result of Whole Effluent Toxicity (WET) test failures with Daphnia pulex, the US Environmental Protection Agency (EPA) required an industrial facility discharging approximately 5 million gallons per day (MGD) of recirculating cooling water obtained from a large freshwater river to conduct a Toxicity Reduction Evaluation (TRE) program. Under the terms of the National Pollutant Discharge Elimination System (NPDES) permit, the facility was required to conduct 48-hour acute toxicity tests with D. pulex and Pimephales promelas (fathead minnow). Although effluent toxicity to D. pulex was consistently observed, no toxicity was induced to the fathead minnow during the TRE program. The situation was further complicated by the fact that the recirculating cooling water was discharged back into the same river. The objectives of the TRE program were to investigate the causes of toxicity, locate potential sources of the suspected toxicant(s), and identify practicable toxicity reduction methodologies to be used. The TRE program approach and results from the associated studies are presented in this report, including a successful remedy for the WET problem.

  12. Acute and environmental toxicity studies with hexazinone.

    PubMed

    Kennedy, G L

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6479506

  13. Multi-level assessment of chronic toxicity of estuarine sediments with the amphipod Gammarus locusta: I. Biochemical endpoints.

    PubMed

    Neuparth, Teresa; Correia, Ana D; Costa, Filipe O; Lima, Gláucia; Costa, Maria Helena

    2005-07-01

    We report on biomarker responses conducted as part of a multi-level assessment of the chronic toxicity of estuarine sediments to the amphipod Gammarus locusta. A companion article accounts for organism and population-level effects. Five moderately contaminated sediments from two Portuguese estuaries, Sado and Tagus, were assessed. Three of them were muddy and two were sandy sediments. The objective was to assess sediments that were not acutely toxic. Three of the sediments met this criterion, the other two were diluted (50% and 75%) with clean sediment until acute toxicity was absent. Following 28-d exposures, the amphipods were analysed for whole-body metal bioaccumulation, metallothionein induction (MT), DNA strand breakage (SB) and lipid peroxidation (LP). Two of the muddy sediments did not cause chronic toxicity. These findings were consistent with responses at organism and population levels that showed higher growth rates and improvement of reproductive traits for amphipods exposed to these two sediments. Two other sediments, one muddy and one sandy, exhibited pronounced chronic toxicity, affecting SB, MT induction (in muddy sediment), survival and reproduction. Potential toxicants involved in these effects were identified. The last sandy sediment exhibited some loss of DNA integrity, however growth was also enhanced. Present results, together with the organism/population-level data, and also benthic communities information, were analysed under a weight-of-evidence approach. By providing evidence of exposure (or lack of it) to contaminants in sediments, the biomarkers here applied assisted in distinguishing toxicants' impacts in test organisms from the confounding influence of other geochemical features of the sediments. PMID:15649528

  14. Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity.

    PubMed

    Wang, Xiaoxue; Mu, Xiaoli; Zhang, Jie; Huang, Qingyu; Alamdar, Ambreen; Tian, Meiping; Liu, Liangpo; Shen, Heqing

    2015-03-01

    Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses. Eighteen differential metabolites were identified, and most of them showed dose-dependent responses to arsenic exposure. Metabolic abnormalities mainly involved lipid metabolism and amino acid metabolism. The metabolic alterations were further confirmed by hepatic gene expression. Expressions of cpt2, lcat, cact, crot and mtr were significantly elevated in high dose groups. This study provides novel evidence to support the association between arsenic exposure and metabolic disruption, and it contributes to understanding the mechanism of chronic arsenic toxicity. PMID:25697676

  15. EFFECTS OF CADMIUM ON RENAL AGING: A CHRONIC CADMIUM FEEDING STUDY IN RATS

    EPA Science Inventory

    Cadmium (Cd) is known to accumulate preferentially in the renal proximal tubules. Animal and human autopsy studies have shown that damage to the renal proximal tubular cells is associated with toxicity from chronic Cd exposure. The present study was undertaken to determine if Cd ...

  16. A phenomenologic study of chronic pain.

    PubMed

    Thomas, S P

    2000-10-01

    Researchers have seldom invited patients with chronic pain to describe their lived experiences. This phenomenologic study involved in-depth interviews with nine women and four men with nonmalignant chronic pain. The essence of participants' experiences was unremitting torment by a force or monster that cannot be tamed. The body was altered and recalcitrant, the life world was shrunken, and the pain set up a barrier that separated them from other people. Time seemed to stop; the future was unfathomable. Findings of this study contribute to the phenomenological literature that explores the human body and its symbolic meanings and call into question the idealized positive depiction of chronic illness that is prominent in contemporary literature. PMID:11094573

  17. In vivo toxicity study of Lantana camara

    PubMed Central

    Pour, Badakhshan Mahdi; Sasidharan, Sreenivasan

    2011-01-01

    Objective To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions Methanolic extract of L. camara is relatively safe on short-term exposure. PMID:23569765

  18. [An acute toxicity study of bromantane].

    PubMed

    Bugaeva, L I; Verovskiĭ, V E; Iezhitsa, I N; Spasov, A A

    2000-01-01

    The toxicity of bromantan was evaluated by conventional acute tests (according to Belen'kiĭ) and by the behavioral activity data (according to Irvin). A method of integral graphical representation of the behavioral activity data is suggested, according to which the results are plotted as a "dose trajectory." Using the dose trajectory constructed for bromantan, the levels of therapeutic, toxic, and lethal doses were calculated. It was established that catecholaminergic effects account for the mechanism of therapeutic action of bromantan, while cholinergic effects determine the drug action in toxic doses. PMID:10763112

  19. Chronic toxicity of tributyltin to development and reproduction of the European freshwater snail Lymnaea stagnalis (L.).

    PubMed

    Leung, Kenneth M Y; Grist, Eric P M; Morley, Neil J; Morritt, David; Crane, Mark

    2007-01-01

    Chronic toxicity, growth and reproduction were measured in the freshwater gastropod Lymnaea stagnalis exposed to waterborne bis(tri-n-butyltin) oxide (TBTO) over a range of four nominal concentrations (0-10microg TBTl(-1)). Egg development was completely inhibited at 10microg TBTl(-1), whilst abnormal embryonic development was observed at 1microg TBTl(-1). For the solvent control and the 0.01microg TBTl(-1)treatment group, normal development of L. stagnalis was observed. Survivorship of hatchlings was significantly reduced by TBT at 1microgl(-1) while inhibition of shell growth of L. stagnalis was also observed at this concentration. The data were used to determine intrinsic growth rates (r) using two theoretical approaches (the Euler-Lotka equation and a Leslie Matrix). Both approaches showed that survival, fecundity and population growth rate were reduced at 1microg TBTl(-1). Interestingly, at 0.01microg TBTl(-1) snails showed a higher fecundity and growth rate than in the solvent control. The TBT concentration at which the r would equal zero (ECr(0)) and the population NOEC (No Observed Effect Concentration) were estimated. The population NOEC was defined as either the lower 95% confidence or lower 95% pointwise percentile limit of the ECr(0). Values obtained using the two different approaches were similar and thus a geometric mean was calculated to obtain a final representative population NOEC value for L. stagnalis of 2745ng TBTl(-1). The present data together with chronic toxicity TBT data for freshwater organisms, obtained from peer-reviewed literature, were used to construct a species sensitivity distribution (SSD). A predicted no effect concentration was then derived from the SSD (hazardous concentration at 5%, i.e., HC5 or 95% protection level). This SSD was compared with the SSD derived from saltwater species datasets. The HC5 value for saltwater species (3.55ng TBTl(-1); lower confidence limit: 1.93ng TBTl(-1)) was significantly lower than that for

  20. Chronic Toxicity of Unweathered and Weathered Macondo Oils to Mysid Shrimp (Americamysis bahia) and Inland Silversides (Menidia beryllina).

    PubMed

    Echols, B; Smith, A; Gardinali, P R; Rand, G M

    2016-07-01

    Chronic, 21-28-day toxicity tests of Macondo source (Massachusetts, or MASS) and weathered Slick A (CTC) and Slick B (Juniper) oils field collected during the 2010 Deepwater Horizon (DWH) Incident in the Gulf of Mexico (GOM) were conducted using standardized procedures. Standard species, Americamysis bahia and Menidia beryllina, were evaluated for changes in survival and growth during daily static-renewal tests. Both species demonstrated an increased sensitivity to low-energy water accommodated fractions (WAFs) of un-weathered MASS oil, with growth and survival decreasing as oil loading rate increased from 0.01 to 1.0 g/L. Survival and growth of mysid shrimp exposed to weathered oil (Slick A and Slick B) did not differ from that of test controls. In contrast, survival and growth of inland silversides declined relative to that of test controls at loading rates of 1 g/L for both weathered oils. Based on the concentration of total polycyclic aromatic hydrocarbons (TPAH42), no observed effect concentrations were lower for inland silverside survival (5.00-7.61 µg/L) and growth (<2.02 to <7.61 µg/L) in chronic exposures to Slick B and Slick A weathered oils compared with mysids (4.75-17.9 µg/L). Average TPAH concentrations in full strength WAFs followed the weathering trend, with 165 ± 17.2, 17.9 ± 0.480, and 4.75 ± 0.521 µg/L for MASS, Slick A, and Slick B oils, respectively. The effect (LOEC, IC25) and no-effect exposure concentrations (in TPAHs) from the standardized laboratory toxicity studies with un-weathered and weathered oils are discussed relative to the actual exposure concentrations in the GOM in 2010. The exposures evaluated in the laboratory toxicity tests represent the highest concentrations of total PAHs that were rarely observed in water column samples collected in the GOM during the release and post release periods of the DWH incident. PMID:27090525

  1. The chronic toxicity of bisphenol A to Caenorhabditis elegans after long-term exposure at environmentally relevant concentrations.

    PubMed

    Zhou, Dong; Yang, Jie; Li, Hui; Cui, Changzheng; Yu, Yunjiang; Liu, Yongdi; Lin, Kuangfei

    2016-07-01

    To investigate biological effects of bisphenol A (BPA) over the long term, the model animal Caenorhabditis elegans was used to conduct the chronic exposure. C. elegans were exposed to BPA (0.0001-10 μM) from L4 larvae to day-10 adult in the present chronic toxicity assay system. Multiple endpoints at the physiological (growth, locomotion behaviors and lifespan), biochemical (lipofuscin accumulation), molecular (stress-related genes expressions), and population (population size) levels were examined. At the physiological level, BPA exposure induced significant negative effects on the indicators. Among the endpoints, head thrash was most sensitive and the detection limit was 0.001 μM. At the biochemical level, BPA exposure induced no significant effects on lipofuscin accumulation. At the molecular level, BPA induced strong stress responses in vivo. At the population level, the population size was significantly decreased in the treatment groups from 0.1 to 10 μM. Compared to the previous short-term toxicity evaluation, long-term exposure to BPA induced a more obvious response at the same concentration, and the phenomenon might be due to cumulative toxic effects. By the Pearson correlation analyses, cep-1 was speculated to act as an important role in BPA-induced chronic toxicity on C. elegans. PMID:27085314

  2. Application of an acute biotic ligand model to predict chronic copper toxicity to Daphnia magna in natural waters of Chile and reconstituted synthetic waters.

    PubMed

    Villavicencio, German; Urrestarazu, Paola; Arbildua, Jose; Rodriguez, Patricio H

    2011-10-01

    The objective of the present study was to assess the predictive capacity of the acute Cu biotic ligand model (BLM) as applied to chronic Cu toxicity to Daphnia magna in freshwaters from Chile and synthetic laboratory-prepared waters. Samples from 20 freshwater bodies were taken, chemically characterized, and used in the acute Cu BLM to predict the 21-d chronic Cu toxicity for D. magna. The half-maximal effective concentration (EC50) values, determined using the Organisation for Economic Co-operation and Development (OECD) 21-d reproduction test (OECD Method 211), were compared with the BLM simulated EC50 values. The same EC50 comparison was performed with the results of 19 chronic tests in synthetic media, with a wide range of hardness and alkalinity and a fixed 2 mg/L dissolved organic carbon (DOC) concentration. The acute BLM was modified only by adjustment of the accumulation associated with 50% of an effect value (EA50). The modified BLM model was able to predict, within a factor of two, 95% of the 21-d EC50 and 89% of the 21-d half-maximal lethal concentrations (LC50) in natural waters, and 100% of the 21-d EC50 and 21-d LC50 in synthetic waters. The regulatory implications of using a slightly modified version of an acute BLM to predict chronic effects are discussed. PMID:21796669

  3. A review of toxicity studies of single-walled carbon nanotubes in laboratory animals.

    PubMed

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa

    2016-02-01

    We summarized the findings of in vivo toxicity studies of single-walled carbon nanotubes (SWCNTs) in laboratory animals. The large majority addressed the pulmonary toxicity of SWCNTs in rodents. Inhalation, pharyngeal aspiration, and intratracheal instillation studies revealed that SWCNTs caused acute and chronic inflammation, granuloma formation, collagen deposition, fibrosis, and genotoxic effects in the lungs. Pulmonary toxicity of well-dispersed SWCNTs was more potent than less dispersed ones. Airway exposure to SWCNTs also induced cardiovascular diseases in mice. Oxidative stress was caused by the administration of SWCNTs. Injected SWCNTs were distributed throughout most of the organs including the brain, mainly retained in the lungs, liver, and spleen, and eliminated through the kidney and bile duct. Orally administered SWCNTs are suggested to be absorbed from the gastrointestinal tract to the blood circulation in mice and rats. Although no definitive study on the carcinogenicity of SWCNTs is available at present, evidence of carcinogenicity has not been reported in toxicity studies cited in this review. Overall, the available data provides initial information on SWCNT toxicity. To further clarify their toxicity and risk assessment, studies should be conducted using well-characterized SWCNTs, standard protocols, and the relevant route and doses of human exposure. PMID:26619783

  4. An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata.

    PubMed

    Quinn, Brian; Gagné, François; Blaise, Christian

    2008-01-25

    Pharmaceuticals previously identified in the effluent from the wastewater treatment plant (WWTP) in Montreal discharging into the St. Lawrence river, were tested for acute and chronic toxicity using the cnidarian Hydra attenuata. Acute toxicity was based on the established technique looking at morphological changes in the Hydra, while recently developed endpoints of feeding behaviour, attachment and growth (hydranth number) were used to measure chronic effects. The compounds under investigation (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfamethoxazole, sulfapyridine, oxytetracycline, novobiocin, trimethoprim and caffeine) were tested individually in controlled laboratory exposures with LC(50) and EC(50) results calculated. All compounds tested had relatively high LC(50) values with gemfibrozil, ibuprofen and naproxen having the lowest at 22.36 mg/L and EC(50) values based on morphology of 1.18 to 2.62 mg/L (all concentrations are nominal). The EC(50) values based on feeding were similar to those based on morphology but with increased sensitivity for carbamazepine, bezafibrate and novobiocin. A trend of a reduction in feeding with deterioration in morphology was observed in the Hydra, with the exception of novobiocin, where a lower than expected EC(50) of 13.53 mg/L was found with no negative effect on morphology. Significant reductions in attachment and hydranth number were seen at concentrations of 1 and 5 mg/L for gemfibrozil and ibuprofen respectively. A toxicity threshold (TT) of 320 microg/L was calculated for ibuprofen, only a factor of 10(2) or 10 higher than the concentration found in the effluent in the present study (1.19 mug/L) and in other Canadian effluents studied (22 microg/L [Brun GL, Bernier M, Losier R, Doe K, Jackman P, Lee HB, Pharmaceutically active compounds in Atlantic Canadian sewage treatment plant effluents and receiving waters and potential for environmental effects as measured by acute and chronic aquatic toxicity

  5. Toxicity studies of a polyurethane rigid foam

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Schneider, J. E.

    1977-01-01

    Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routine screening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routine screening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

  6. Reproductive and developmental toxicity testing: Examination of the extended one-generation reproductive toxicity study guideline.

    PubMed

    Saghir, Shakil A; Dorato, Michael A

    2016-08-01

    An important aspect of safety assessment of chemicals (industrial and agricultural chemicals and pharmaceuticals) is determining their potential reproductive and developmental toxicity. A number of guidelines have outlined a series of separate reproductive and developmental toxicity studies from fertilization through adulthood and in some cases to second generation. The Extended One-Generation Reproductive Toxicity Study (EOGRTS) is the most recent and comprehensive guideline in this series. EOGRTS design makes toxicity testing progressive, comprehensive, and efficient by assessing key endpoints across multiple life-stages at relevant doses using a minimum number of animals, combining studies/evaluations and proposing tiered-testing approaches based on outcomes. EOGRTS determines toxicity during preconception, development of embryo/fetus and newborn, adolescence, and adults, with specific emphasis on the nervous, immunological, and endocrine systems, EOGRTS also assesses maternal and paternal toxicity. However, EOGRTS guideline is complex, criteria for selecting doses is unclear, and monitoring systemic dose during the course of the study for better interpretation and human relevance is not clear. This paper discusses potential simplification of EOGRTS, suggests procedures for relevant dose selection and monitors systemic dose at multiple life-stages for better interpretation of data and human relevance. PMID:27074386

  7. Skin temperature recording with phosphors: toxicity studies on animals.

    PubMed

    Derse, P H; Alt, L L

    1966-08-20

    In a previous communication in this journal, a method was described for converting invisible thermal patterns of the human skin into a detailed visible picture. At that time, the question of possible toxicity of the thermographic phosphor was raised. Toxicity studies conducted on laboratory animals indicate that the probability of toxic side reactions resulting from the use of zinc-cadmium sulfide phosphor spray is very low. PMID:5943198

  8. Toxicity studies of mild gasification products

    SciTech Connect

    Ong, T.M.; Whong, W.Z.; Ma, J.; Zhong, B.Z.; Bryant, D.

    1992-01-01

    The objectives of this project are: (1) to perform mutagenicity studies with the Ames Salmonella/microsomal assay system on coal liquids produced by mild gasification from different coals and/or processing conditions, (2) to determine whether coal liquids which are mutagenic to bacteria are also genotoxic to mammalian cells, (3) to establish correlations between mutagenicity, aromaticity, and boiling point range of coal liquids, and (4) to identify the chemical classes which are likely to be responsible for the mutagenic activity of gasification products. Four of the seven samples tested so far failed to demonstrate any mutagenic activity under any conditions tested. Those samples were SHELL[number sign]830331, MG-122IBP-420[degree]F, MG-122 420--720[degree]F, and MG-122 720[degree]F+. Table 1 summarizes the results from all samples tested in DMSO and Tween 80. When solvated in DMSO, MG-119 and MG-120 composite materials displayed slight, but ultimately insignificant, genotoxic activity on TA98 and TA1OO in the presence of S9. When Tween 80 was used as the solvent, MG-119 and MG-120 displayed slight, but significant, geno-toxic activity on TA98 with S9 (Figure 4). CTC[number sign]11 in DMSO displayed significant genotoxic activity on both TA98 and TA1OO with and without S9. The activity was higher on TA98 than TA100, and higher with S9 than without, primarily indicating the presence of indirect-acting frameshift mutagen. The results of the testing on CTC[number sign]11 were similar for both solvents, DMSO and Tween 80 (Table 2).

  9. Toxicity studies of mild gasification products

    SciTech Connect

    Ong, T.M.; Whong, W.Z.; Ma, J.; Zhong, B.Z.; Bryant, D.

    1992-11-01

    The objectives of this project are: (1) to perform mutagenicity studies with the Ames Salmonella/microsomal assay system on coal liquids produced by mild gasification from different coals and/or processing conditions, (2) to determine whether coal liquids which are mutagenic to bacteria are also genotoxic to mammalian cells, (3) to establish correlations between mutagenicity, aromaticity, and boiling point range of coal liquids, and (4) to identify the chemical classes which are likely to be responsible for the mutagenic activity of gasification products. Four of the seven samples tested so far failed to demonstrate any mutagenic activity under any conditions tested. Those samples were SHELL{number_sign}830331, MG-122IBP-420{degree}F, MG-122 420--720{degree}F, and MG-122 720{degree}F+. Table 1 summarizes the results from all samples tested in DMSO and Tween 80. When solvated in DMSO, MG-119 and MG-120 composite materials displayed slight, but ultimately insignificant, genotoxic activity on TA98 and TA1OO in the presence of S9. When Tween 80 was used as the solvent, MG-119 and MG-120 displayed slight, but significant, geno-toxic activity on TA98 with S9 (Figure 4). CTC{number_sign}11 in DMSO displayed significant genotoxic activity on both TA98 and TA1OO with and without S9. The activity was higher on TA98 than TA100, and higher with S9 than without, primarily indicating the presence of indirect-acting frameshift mutagen. The results of the testing on CTC{number_sign}11 were similar for both solvents, DMSO and Tween 80 (Table 2).

  10. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    PubMed

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert