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Sample records for chronic toxicity studies

  1. Chronic arsenic toxicity: studies in West Bengal, India.

    PubMed

    Guha Mazumder, Debendranath; Dasgupta, U B

    2011-09-01

    Chronic arsenic toxicity (arsenicosis) as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 μg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been found to be

  2. 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.

  3. Chronic toxicity study of cyclohexanone in rats and mice.

    PubMed

    Lijinsky, W; Kovatch, R M

    1986-10-01

    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  4. 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.

  5. Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats

    PubMed Central

    Koontongkaew, Sittichai; Poachanukoon, Orapan; Sireeratawong, Seewaboon; Dechatiwongse Na Ayudhya, Thaweephol; Khonsung, Parirat; Jaijoy, Kanjana; Soawakontha, Ruedee; Chanchai, Monraudee

    2014-01-01

    Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females. PMID:27379341

  6. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

    PubMed

    Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

    2014-03-01

    The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

  7. A system for reconstituting special water qualities for use in chronic toxicity studies

    USGS Publications Warehouse

    Hamilton, Steven J.; Faerber, Neil L.; Buhl, Kevin J.

    1989-01-01

    A water treatment system and procedure are described that are designed for preparing large quantities of reconstituted water with specific chemical and physical characteristics for use in chronic toxicity studies with fish and invertebrates. Water treatment units produce high-purity water in large quantities for storage in high-density cross-linked polyethylene tanks, where it is combined with various salts to reconstitute an appropriate experimental water quality that simulates potential environmental conditions for use as the test medium in an intermittent-flow proportional diluter. Several water quality characteristics for the source water and the receiving water, and respective flow rates must be considered when one calculates the chemical constituents that must be added to closely simulate the water in a potential environmental situation. The water treatment system and procedure have been used to produce four differently reconstituted experimental waters that were used in 60- to 90-day early life stage chronic toxicity studies with fish. Of the ten water quality characteristics measured in the experimental waters during the studies, eight had a coefficient of variation of <5%-indicating that the various physiochemical characteristics could be precisely reproduced throughout long-term exposure studies.

  8. Acute and sub-chronic toxicity study of diaveridine in Wistar rats.

    PubMed

    Wang, Xu; Su, Shijia; Ihsan, Awais; Huang, Qin; Chen, Dongmei; Cheng, Guyue; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-10-01

    Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day). PMID:26209270

  9. Acute and sub-chronic toxicity study of diaveridine in Wistar rats.

    PubMed

    Wang, Xu; Su, Shijia; Ihsan, Awais; Huang, Qin; Chen, Dongmei; Cheng, Guyue; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2015-10-01

    Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used as anticoccidial drug and antibacterial synergist. However, few studies have been performed to investigate its toxicity. To provide detailed toxicity with a wide spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in males, and chromodacryorrhea was noted in some females before their death. In the sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0-23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease in body weights in both genders at 1150 and 2000 mg/kg groups and significant increases in relative weights of brain in both genders, liver in females, kidneys and testis in males, alkaline phosphatase and potassium in both genders at 2000 mg/kg diet were noted. Significant decrease in absolute weights of several organs, hemoglobin and red blood cell count in both genders, albumin and total protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys, cell swelling of the glomerular zone in the adrenals and inflammation in the liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day).

  10. 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

  11. 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

  12. 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 ...

  13. Occurrence of Pineal Gland Tumors in Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats.

    PubMed

    Treumann, Silke; Buesen, Roland; Gröters, Sibylle; Eichler, Jens-Olaf; van Ravenzwaay, Bennard

    2015-08-01

    Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and unrelated to treatment. The morphology and immunohistochemical evaluation led to the diagnosis malignant pinealoma. The main characteristics that were variably developed within the tumors were the following: cellular atypia, high mitotic index, giant cells, necrosis, Homer Wright rosettes, Flexner-Wintersteiner rosettes and pseudorosettes, positive immunohistochemical reaction for synaptophysin, and neuron-specific enolase. The pineal gland is not a protocol organ for histopathological examination in carcinogenicity studies. Nevertheless, the pineal gland can occasionally be encountered on the routine brain section or if it is the origin of a tumor protruding into the brain, the finding will be recorded. Therefore, although known to be a rare tumor in rats, pineal neoplasms should be included in the list of possible differential diagnoses for brain tumors, especially when the tumor is located in the region of the pineal body.

  14. Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats.

    PubMed

    Butenhoff, John L; Chang, Shu-Ching; Olsen, Geary W; Thomford, Peter J

    2012-03-11

    To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K⁺ PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K⁺ PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K⁺ PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K⁺ PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p=0.046) and females (p=0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to terminal sacrifice. The only hepatocellular carcinoma observed was in a 20 ppm dose group female. There were no treatment-related findings for thyroid tissue in rats fed K⁺ PFOS through study termination; however, male rats in the 20 ppm Recovery group had statistically significantly increased thyroid follicular cell adenoma, which was considered spurious. There was no evidence of kidney or bladder effects. In rats, the

  15. Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice.

    PubMed

    Hack, R; Ebert, E; Leist, K H

    1995-11-01

    The insecticide endosulfan was evaluated for chronic toxicity and carcinogenicity in long-term feeding studies in both Sprague-Dawley rats and NMRI mice. Dietary concentrations of the test substance were administered to rats at 0, 3, 7.5, 15 and 75 ppm and to mice at 0, 2, 6 and 18 ppm for 24 months each. In the rat study, only the treatment with the highest dose caused a significant reduction of body weight gains of the males and females at 75 ppm. The increased incidence of enlarged kidneys seen at autopsy at 75 ppm in females, and the slightly increased incidence of progressive glomerulonephrosis and slightly increased incidence of renal aneurysms seen histopathologically in the 75 ppm males, make the kidney the target organ in rats. On the basis of these findings a dietary concentration of 15 ppm is considered to be the no-observed-effect level (NOEL) in rats, equivalent to a daily test substance intake of 0.6 mg/kg body weight in males and 0.7 mg/kg body weight in females. In the mouse study, the treatment with 18 ppm caused a significant increase of mortality in the females and a slight (in the first third of the study, significant) reduction of body weight gain in males. Since there were no other substance-related findings, the dietary concentration of 6 ppm is considered to be the NOEL in mice, equivalent to a daily test substance intake of 0.84 mg/kg body weight in males and 0.97 mg/kg body weight in females. An evaluation of all relevant tumour data gained in both studies revealed no differences between control and treated groups. It was concluded, therefore, that endosulfan has no carcinogenic potential.

  16. 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

  17. Acute and chronic arsenic toxicity.

    PubMed

    Ratnaike, R N

    2003-07-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

  18. Acute and chronic arsenic toxicity

    PubMed Central

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water. PMID:12897217

  19. 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

  20. 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.

  1. Safety assessment of dietary administered paprika color in combined chronic toxicity and carcinogenicity studies using F344 rats.

    PubMed

    Inoue, T; Umemura, T; Maeda, M; Ishii, Y; Okamura, T; Tasaki, M; Nishikawa, A

    2008-08-01

    Combined chronic toxicity and carcinogenicity studies of paprika color, used as a food additive in various countries, were performed in male and female F344 rats. Dietary concentrations of 0%, 0.62%, 1.25%, 2.5% and 5% were applied in a 52-week toxicity study and 0%, 2.5% and 5% in a 104-week carcinogenicity study. Treatment with paprika color caused a significant increase in incidence of hepatocellular vacuolation in 5% males, but no toxicological effects were found with reference to survival rates, body weights, hematological or serum biochemical parameters and organ weights at any dose level in either sex in the chronic toxicity study. Also, paprika color did not induce specific tumors nor did it exert significant influence on the development of spontaneous tumors in any of the organs examined in the carcinogenicity study. In conclusion, based on slight histopathological changes observed in 5% male livers, the no-observed-effect level (NOEL) was estimated to be 2.5% in the diet (1,253 mg/kg bw/day) and the no-observed-adverse-effect level (NOAEL) was determined to be 5% in the diet (2,388 mg/kg bw/day) for male rats, and for females, the NOEL was concluded to be 5% in the diet (2,826 mg/kg bw/day). Additionally, paprika color was not carcinogenic to male and female F344 rats under the present experimental conditions.

  2. Studying toxicity

    USGS Publications Warehouse

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  3. A chronic toxicity/carcinogenicity study of FD & C Yellow No. 5 (tartrazine) in mice.

    PubMed

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5, 1.5 or 5.0% in a long-term toxicity/carcinogenicity study. Each group consisted of 60 males and 60 females. Maximum exposure was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse effect level established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively.)

  4. 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

  5. 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

  6. 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.

  7. A chronic inhalation toxicity/oncogenicity study of methylethylketoxime in rats and mice.

    PubMed

    Newton, P E; Wooding, W L; Bolte, H F; Derelanko, M J; Hardisty, J F; Rinehart, W E

    2001-12-01

    To evaluate the oncogenic potential of methylethylketoxime (MEKO), CD-1 mice (50/sex/group) and F-344 rats (50/sex/group) were coexposed 6 h/day, 5 days/wk for 18 mo (mice) or 26 mo (rats) via whole-body inhalation exposures to target vapor concentrations of 0, 15, 75, and 375 ppm (actual concentrations of 0, 15 +/- 1, 75 +/- 2, or 374 +/- 10 ppm). Satellite groups of rats and mice (10/sex/group/interval) were exposed for 12 mo (mice) and 3, 12, or 18 mo (rats) to evaluate chronic toxicity. Methyl ethyl ketone (MEK), a possible hydrolysis product of MEKO, was present at less than 1%. Treatment-related effects included increased body weight (male rats only), methemoglobin formation, hematology and clinical chemistry changes, increased liver weight, and increased spleen and testes weights (rats only). A high incidence of cataracts and corneal dystrophy occurred in both control and MEKO-exposed rats, with an earlier appearance and slightly higher incidence for these ocular lesions in MEKO-exposed animals compared to controls. Degenerative and reparative changes of the olfactory epithelium in the nasal turbinates, primarily limited to the dorsal meatus, occurred in both rats (75 and 374 ppm) and mice (15, 75, and 374 ppm). In addition, in the mice, liver changes included increased incidences of pigment in reticuloendothelial cells, centilobular hypertrophy, granulomatous inflammation, and a slightly increased incidence of necrosis (75 and 374 ppm). An increase in hepatocellular carcinomas occurred in male mice at 374 ppm. Additional MEKO-related findings in the rat included congestion of the spleen with pigment in reticuloendothelial cells and extramedullary hematopoiesis and a decreased incidence of lymphoreticular mononuclear cell leukemia. Effects observed in the liver of the rats included decreases in the incidence of both peribiliary fibrosis and hyperplasia/proliferation of the biliary duct, an increase of spongiosis hepatis in males, and an increase in the

  8. Chronic toxicity/carcinogenicity studies of FD & C Yellow No. 5 (tartrazine) in rats.

    PubMed

    Borzelleca, J F; Hallagan, J B

    1988-03-01

    FD & C Yellow No. 5 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies were conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at levels of 0.0, 0.0, 0.1, 1.0 or 2.0% ('original study') and 0.0 or 5.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels with 70 rats of each sex/group, including the three control groups. The maximum exposure to the colouring was 113 and 114 wk for males and females, respectively, in the 'original' study and 122 and 125 wk for males and females, respectively, in the 'high-dose' study. No compound-related effects were noted. The no-adverse-effect level found in this study was 5.0% in the diet providing an average intake of 2641 and 3348 mg/kg/day for male and female rats, respectively.

  9. Acute and chronic toxicity study of the water accommodated fraction (WAF), chemically enhanced WAF (CEWAF) of crude oil and dispersant in the rock pool copepod Tigriopus japonicus.

    PubMed

    Lee, Kyun-Woo; Shim, Won Joon; Yim, Un Hyuk; Kang, Jung-Hoon

    2013-08-01

    We determined the toxicity of the water accommodated hydrocarbon fraction (WAF), two chemically enhanced WAFs (CEWAFs; CEWAF-C, Crude oil+Corexit 9500 and CEWAF-H, Crude oil+Hiclean) of crude oil and two dispersants (Corexit 9500 and Hiclean) to the rock pool copepod Tigriopus japonicus. In the acute toxicity test, Corexit 9500 was the most toxic of all the chemicals studied. The nauplius stage of T. japonicus was more susceptible to the toxic chemicals studied than the adult female. The toxicity data using the nauplius stage was then considered as baseline to determine the spiking concentration of chemicals for chronic toxicity tests on the copepod. As the endpoints in the chronic toxicity test, survival, sex ratio, developmental time and fecundity of the copepod were used. All chemicals used in this study resulted in increased toxicity in the F1 generation. The lowest-observed-adverse-effect (LOAE) concentrations of WAF, CEWAF-H, CEWAF-C, Hiclean and Corexit 9500 were observed to be 50%, 10%, 0.1%, 1% and 1%, respectively. The results in present study imply that copepods in marine may be negatively influenced by spilled oil and dispersant.

  10. Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats

    PubMed Central

    TIAN, YE; TENG, LI-RONG; WANG, ZHEN-ZUO; ZHAO, MIN; MENG, QING-FAN; LU, JIA-HUI; TIAN, JIAN-MING; ZHANG, WEI-WEI; ZHENG, XIAOYI; WANG, DI; TENG, LE-SHENG

    2015-01-01

    Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain. PMID:26136985

  11. 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.

  12. Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.

    PubMed

    Paul, P C; Chattopadhyay, A; Dutta, S K; Mazumder, D N; Santra, A

    2000-07-01

    Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes. We have studied skin biopsies from 42 patients of CAT. Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases. Squamous cell carcinoma was present in 2, basisquamous in 1 and basal cell carcinoma in 1 case. Changes of skin lesions after drug DMSA and DMPS therapy compared to placebo were studied. The result was inconclusive. Proliferative activity of skin lesions in CAT were studied by AgNOR stain to assess the biological behaviour of the lesions. AgNOR score showed--normal control 1.08, benign changes (e.g. Hyperkeratosis, parakeratosis, acanthosis, papillomatosis etc.) without dysplasia--1.35, mild to moderate dysplasia--1.735, severe dysplasia--3.0 and carcinoma--3.56. Thus, AgNOR score gives some idea on the biological behaviour of CAT lesions. It is suggested that AgNOR staining should be done regularly along with H&E staining for proper assessment of the cases.

  13. 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

  14. Chronic copper toxicity in a dairy herd

    PubMed Central

    Perrin, David J.; Schiefer, H. Bruno; Blakley, Barry R.

    1990-01-01

    The addition of excessive copper to a commercially prepared dairy ration caused chronic copper toxicity in a dairy herd. A formulation error by a feed company resulted in copper levels of 800 to 1,000 mg/kg in the “as fed concentrate,” amounting to about 400-500 mg copper/kg of the whole ration. Five animals died with typical signs of acute copper toxicity, including intravascular hemolysis and methemoglobinemia. A further 39 cows died on the farm from a combination of debilitation and secondary infectious causes, and 215 were sent to slaughter because of debilitation and poor milk production. The mortality of calves born to dams that had been fed the toxic concentrate was approximately 50%. We postulate that dairy cows, particularly pregnant cows, may be more susceptible to copper toxicity than other cattle, and suggest reexamination of the presently allowable maximum levels of copper supplementation of diets for dairy cattle. PMID:17423660

  15. Chronic Fluoride Toxicity: Dental Fluorosis

    PubMed Central

    DenBesten, Pamela; Li, Wu

    2012-01-01

    further studies are done, we will better understand the mechanisms responsible for dental fluorosis. PMID:21701193

  16. Multiple-dose chronic inhalation toxicity study of size-separated kaolin refractory ceramic fiber in male Fischer 344 rats.

    PubMed

    Mast, R W; McConnell, E E; Hesterberg, T W; Chevalier, J; Kotin, P; Thevenaz, P; Bernstein, D M; Glass, L R; Miiller, W; Anderson, R

    1995-01-01

    Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure an in an effort to define the dose-response, as a follow up to a maximum tolerated dose [30 mg/m(3)] study in rats (Mast et al., 1995), a multiple dose chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Four groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 3, 9, or 16 mg/m(3)(approximately 36, 91, and 162 fibers/cm(3)) of kaolin-based "size-selected" RCF fibers (approximately 1 µm in diameter and approximately 20 µm in length) for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and sacrificed (30 mo). Croups of 3-6 animals were sacrificed at 3, 6, 12, 18, and 24 mo to follow the progression of pulmonary lesions and to determine fiber lung burdens. Additional groups of 3-6 rats were removed from exposure at 3, 6, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. A dose-related increase in fiber lung burden was observed. Lung burdens at 24 mo ranged from 5.6 × 10(4) to 27.8 × 10(4) fibers/mg dry lung tissue. Significant increases in lung weights and lung to body weight ratios were seen in the high-dose group. Treatment-related lesions were restricted to the lungs. To some extent, all doses of RCF resulted in minimal to mild macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 12 mo of exposure. Interstitial fibrosis was observed at 12 mo in the 9 and 16 mg/m(3) groups but not in the low-dose group at any time point. A minimal amount of focal pleural fibrosis was first observed at 12 mo in the 9 and 76 mg/m(3) dose groups and progressed to a mild severity in the high

  17. Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats.

    PubMed

    Mast, R W; McConnell, E E; Anderson, R; Chevalier, J; Kotin, P; Bernstein, D M; Thevenaz, P; Glass, L R; Miiller, W C; Hesterberg, T W

    1995-01-01

    Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure, a chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Five groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m(3) (approximately 220 fibers/cm(3)) of three types [kaolin-based, high-purity, and aluminum zirconia silica (AZS)] of "size-selected" RCF fibers (approximately 1µ in diameter and approximately 20 um in length) and an "after-service" heat-treated (2400°F for 24 h) kaolin-based fiber for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and then sacrificed at 30 mo. A positive control group of 80 F344 rats was exposed to 10 mg/m(3) chrysotile asbestos. Croups of 3-6 animals were sacrificed at 3, 6, 9, 12, 15, 18, and 24 mo to follow the progression of lesions and to determine fiber lung burdens. Additional groups of 3 rats were removed from exposure at 3, 6, 9, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. Lung burdens increased rapidly for all RCFs, appearing to plateau by about 12 mo. By 24 mo, lung burdens ranged from 2.6 to 9.6 × 10(5) fiberslmg of dry lung tissue for the RCFs tested. Treatment-related lesions were restricted to the lungs. To some extent all types of RCF resulted in macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 3 mo of exposure. Interstitial fibrosis was observed at 6 mo for all types of RCF, except the "after-service" fiber where fibrosis was not seen until 12 mo. The lesions progressed in severity until 12-15 mo, after which they plateaued. A minimal amount of focal pleural fibrosis was first observed at 9 mo and progressed to a

  18. 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.

  19. Overlapping but distinct effects of genistein and ethinyl estradiol (EE2) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies

    PubMed Central

    Delclos, K. Barry; Weis, Constance C.; Bucci, Thomas J.; Olson, Greg; Mellick, Paul; Sadovova, Natalya; Latendresse, John R.; Thorn, Brett; Newbold, Retha R.

    2009-01-01

    Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE2 (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE2 at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE2 significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations. PMID:19159674

  20. [Acute and chronic toxicity of saponins from Argania spinosa].

    PubMed

    Alaoui, K; Belabbes, M; Cherrah, Y; Hassar, M; Charrouf, Z; Amarouch, H; Roquebert, J

    1998-01-01

    We evaluated the acute and chronic experimental toxicity of a water extract of saponins from Argania spinosa following oral and intraperitoneal (i.p.) administration in mice (Iops Ofa) and rats (Wistar). The DL50 obtained were 79 mg/kg for the i.p. route and 1,300 mg/kg for the oral route. For the chronic toxicity studies, we administred 100 and 200 mg/kg orally once a day during a 3 month period. There was a decrease in blood sugar in the third month of each therapy. Blood creatinine levels increased, thus evoking a renal pathology. A slight increase in transaminases levels was not significatif. Hematologic parameters were unchanged during the treatment and the histopathologic study showed hepatic glycogen decrease and a focal renal tube deterioration. PMID:9805821

  1. Psychologic sequelae of chronic toxic waste exposure.

    PubMed

    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. PMID:1738876

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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...

  9. 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

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

    PubMed Central

    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 should

  11. 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

  12. 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

  13. Chronic toxicity of diethyl phthalate-A three generation lactational and gestational exposure study on male Wistar rats.

    PubMed

    Pereira, Contzen; Mapuskar, Kranti; Rao, C Vaman

    2007-05-01

    Diethyl phthalate (DEP) is widely used in the perfume industry as a vehicle for fragrances and in personal care products making human exposure of DEP significant to adults as well as neonatals, as confirmed by levels recorded in blood as well as breast milk samples of human populations in some parts of the world. Therefore, a study was undertaken to understand the toxic effect of DEP over three generations in male Wistar rats. Healthy male and female albino rats of Wistar strain weighing 75-100g (6-7 weeks old) were randomly assigned to two groups of six each. Group I (Control) male and female rats were fed on normal diet and water ad libitum. Group II (DEP) male and female rats were given DEP dissolved in corn oil mixed with the diet at 50mg/kg of the diet/day. Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of the parental generation. The F1 and F2 generation pups were then segregated on the basis of their sex and six male and female pups of both generations were allowed to grow till they were 75-100g in weight. The treatment was then carried out similar to the parental generation but with reduced dose of 25mg/kg of the diet/day for F1 generation and 10mg/kg of the diet/day for F2 generation. Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP was continued throughout mating, gestation (21 days) until termination at weaning (21 days), which was 150 days of total treatment period of the F1 and F2 generation. Liver and serum ALT, AST and triglycerides were significantly increased over the three generations, which was much more significant in the F2 generation DEP treated group. The serum cholesterol and liver glutathione and glutathione reductase showed a significant decrease over the three generations, which was much more significant in the F2 generation DEP

  14. Chronic toxicity and tumorigenicity study of aluminum potassium sulfate in B6C3F1 mice.

    PubMed

    Oneda, S; Takasaki, T; Kuriwaki, K; Ohi, Y; Umekita, Y; Hatanaka, S; Fujiyoshi, T; Yoshida, A; Yoshida, H

    1994-01-01

    The tumorigenic potential of aluminum potassium sulfate [A1K (SO4)2 12H2O, APS], a compound which exists widely in the environment, was investigated in B6C3F1 mice. APS was administered in the diet for 20 months at dose levels of 1.0, 2.5, 5.0 and 10.0% (w/w). One group receiving the basal diet served as the control. Body weight gain in both sexes was decreased in the 10.0% APS treated group, and increased in the 1.0 and 2.5% APS treated groups. The survival rates at the end of the dosing period were 73.3% (male) and 78.3% (female) in the control group, and 86.7-95.0% (male) and 86.7-91.7% (female) in the APS treated groups. The survival rate showed a tendency to increase in both sexes in all the APS treated groups. In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group. The incidence of hepatocellular carcinoma was significantly decreased in females in all groups including the control group. As regards the nontumorous pathology, the incidence of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease in males in the APS treated groups. A comparison between the sexes revealed a significant decrease in the incidence of hepatocytic anisonucleosis, myocardial eosinophilic cytoplasm and acinar cell vacuolation of the submandibular gland in the females; and lymphocyte infiltration in renal cortex and pelvis, and vacuolation of cerebellar white matter were noted in the males. The results of the present study indicate that long-term administration of APS does not exert tumorigenic or any other toxic actions in B6C3F1 mice.

  15. 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

  16. Lead Toxicity Resulting from Chronic Ingestion of Opium

    PubMed Central

    Jalili, Mohammad; Azizkhani, Reza

    2009-01-01

    A 32-year-old man presented to the emergency department (ED) with lower abdominal pain and constipation. He related chronic ingestion of large amounts of opium. Physical examination showed mild abdominal tenderness and gingival discoloration. Diagnostic studies showed a mild hypochromic, microcytic anemia with basophilic stippling of the red blood cells. Abdominal imaging showed no intra-abdominal pathology. A diagnosis of lead toxicity was confirmed through serum lead levels. The patient was put on chelation therapy and his signs and symptoms started to resolve. As a comprehensive search for other sources of lead was unsuccessful, opium adulterants were considered as the culprit. Chemical analysis of the opium confirmed this. Contaminated drugs have been reported as a source of exposure to toxins such as arsenic or lead. While other reports deal with patients from clinics, this report illustrates lead toxicity from ingestion of contaminated opium in the ED. PMID:20046241

  17. 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/.

  18. 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.

  19. 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...

  20. Occupation and the risk of chronic toxic leukoencephalopathy.

    PubMed

    Filley, Christopher M

    2015-01-01

    Among the hundreds of environmental insults capable of inducing nervous system injury, a small number can produce clinically significant damage to the brain white matter. The use of magnetic resonance imaging (MRI) in affected individuals has greatly illuminated this previously obscure area of neurotoxicology. Toxic leukoencephalopathy has acute and chronic forms, in both of which cognitive dysfunction is the major clinical manifestation. Chronic toxic leukoencephalopathy (CTL) has been most thoroughly described in individuals with intense and prolonged exposure to leukotoxins, but the consequences of lesser degrees of exposure are not well understood. Rare cases of CTL have been reported in workers exposed to culpable leukotoxins, but study of this syndrome is hindered by many confounds such as uncertain level of toxin exposure, the presence of multiple toxins, vague dose-response relationship, comorbid medical or neurologic disorders, psychiatric illness, and legal issues. The risk of CTL in workers is low, although it is not possible to determine quantitative risk estimates. More knowledge can be expected with the application of advanced MRI techniques to the assessment of workers who may have been exposed to known or potential leukotoxins. Preventive measures for avoiding workplace CTL will be informed by clinical assessment involving the use of advanced neuroimaging and neuropsychologic evaluation in combination with accurate measurement of leukotoxin exposure. PMID:26563784

  1. Chronic toxicity evaluation of wastewater treatment plant effluents with bioluminescent bacteria: A comparison with invertebrates and fish

    SciTech Connect

    Sweet, L.I.; Travers, D.F.; Meier, P.G.

    1997-10-01

    The use of bioluminescent bacteria in chronic toxicity testing is a potentially useful yet unexplored tool in whole effluent biomonitoring. The purpose of this study was to determine the chronic toxicity of 14 different wastewater treatment plant effluents to Chronic Microtox{reg_sign} bacteria (Vibrio fischeri), a cladoceran (Ceriodaphnia dubia), and a minnow (Pimephales promelas). The invertebrate and fish have been utilized extensively for the evaluation of effluents and in establishing water quality criteria. The results of this study suggest that the 22-h Microtox Chronic Toxicity Test may correlate well with the most sensitive chronic no-observed-effect concentration value of the three-brood C. dubia test.

  2. Human diets cooked by microwave or conventionally: comparative sub-chronic (13-wk) toxicity study in rats.

    PubMed

    Jonker, D; Til, H P

    1995-04-01

    To compare the possible effects of microwave and conventional cooking on a range of common dietary components, mixed human diets containing beef, potatoes and vegetables were fed to groups of 10 male and 10 female Wistar rats for 13 wk. The diet ingredients were cooked by either of the methods in a normal and an abused manner, the latter consisting of the normal treatment followed by two cycles of reheating to approximately 85 degrees C and cooling. The cooked ingredients were freeze-dried, ground and mixed with supplements of vitamins and minerals to meet the rat requirements. An additional control group was fed a cereal-based rodent diet. Criteria to assess toxicity included clinical observations, ophthalmoscopy, growth, food and water intake, haematology, clinical chemistry, urinalysis, organ weights, micronucleated erythrocytes in bone marrow, gross examination at autopsy and microscopic examination of a wide range of organs. The results indicate no adverse effects of the diets cooked by microwave compared with those cooked conventionally. PMID:7737598

  3. 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.

  4. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... planned, the number should be increased by the number of animals scheduled to be sacrificed during the... used in administering the test substance, a vehicle control group. If the toxic properties of the... given by gavage or capsule for a period of at least 12 months. (B) If the......

  5. 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

  6. [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

  7. 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...

  8. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for asexual (parthenogenic) reproduction. For automatic feeding devices, a suggested rate is 5 to 7 mg... cultured to produce test organisms through reproduction. (2) Chronic toxicity test means a method used to... an extended period of time. In this test guideline, mortality and reproduction (and...

  9. 40 CFR 797.1330 - Daphnid chronic toxicity test.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for asexual (parthenogenic) reproduction. For automatic feeding devices, a suggested rate is 5 to 7 mg... cultured to produce test organisms through reproduction. (2) Chronic toxicity test means a method used to... an extended period of time. In this test guideline, mortality and reproduction (and...

  10. Chronic toxicity studies on 1,3,5-trinitrobenzene in Fischer 344 rats. Final report, 1 May 1993-30 April 1995

    SciTech Connect

    Reddy, T.V.; Daniel, F.B.; Olson, G.R.; Wiechman, B.; Torsella, J.

    1996-02-01

    Chronic toxic effects of I ,3,5-tnnitriotrobenzene (TNB) in male and female Fischer rats were evaluated by feeding certified powdered laboratory chow diet supplemented with varied concentrations of TNB (0, 5, 60 and 300 mg/kg diet). The study was designed to accommodate three interim sacrifices (10 rats/group/sex) at 90, 180 and 365 days. The final sacrifice was performed after two years. All data related to these interim sacrifices are presented independently in appendices J to L. The calculated average TNB consumption for females was 0.23, 2.68 and 13.31 mg/kg/day and was 0.22, 2.64 and 13.44 mg/kg/day for males. Terminal body weights were significantly decreased in both sexes in the 300 mg/kg group. Relative spleen weights were decreased in both sexes in the 300 mg/kg group while brain weights were increased in females in this same group. Methemoglobin was increased in both sexes in the 300 mg/kg group while other hematological effects noted at the interim sacrifice times were not evident at two years. Histopathological examinations suggested treatment related changes in both sexes involving the kidneys (cytoplasmic/hyaline droplets) in the 60 and 300 mg/kg groups and the spleen (erythroid cell hyperplasia and pigment deposition) in the 300 mg/kg group. The cytoplasmic/hyaline droplets were characterized by immunohistochemistry as alpha-2u-globulin. These renal droplets were also noted at the interim sacrifice times. A no observed adverse effect level (NOAEL) was established in this study at 2.68 mg/kg b.w./day for F-344 rats administered TNB for two years.

  11. Mustard gas toxicity: the acute and chronic pathological effects.

    PubMed

    Ghabili, Kamyar; Agutter, Paul S; Ghanei, Mostafa; Ansarin, Khalil; Shoja, Mohammadali M

    2010-10-01

    Ever since it was first used in armed conflict, mustard gas (sulfur mustard, MG) has been known to cause a wide range of acute and chronic injuries to exposure victims. The earliest descriptions of these injuries were published during and in the immediate aftermath of the First World War, and a further series of accounts followed the Second World War. More recently, MG has been deployed in warfare in the Middle East and this resulted in large numbers of victims, whose conditions have been studied in detail at hospitals in the region. In this review, we bring together the older and more recent clinical studies on MG toxicity and summarize what is now known about the acute and chronic effects of the agent on the eyes, skin, respiratory tract and other physiological systems. In the majority of patients, the most clinically serious long-term consequences of MG poisoning are on the respiratory system, but the effects on the skin and other systems also have a significant impact on quality of life. Aspects of the management of these patients are discussed.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Predictors for Chronic Urinary Toxicity After the Treatment of Prostate Cancer With Adaptive Three-Dimensional Conformal Radiotherapy: Dose-Volume Analysis of a Phase II Dose-Escalation Study

    SciTech Connect

    Harsolia, Asif; Vargas, Carlos; Yan Di; Brabbins, Donald; Lockman, David; Liang Jian; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro; Kestin, Larry L.

    2007-11-15

    Purpose: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. Methods and Materials: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. Results: The 3-year rates of Grade {>=}2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving {>=}30 Gy (V30) and {>=}82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade {>=}2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade {>=}2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade {>=}2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade {>=}2 and Grade 3 chronic urinary toxicity. Conclusions: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm{sup 3} and the V82 to <7 cm{sup 3} when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.

  18. Comparison of short-term chronic and chronic silver toxicity to fathead minnows in unamended and sodium chloride-amended waters.

    PubMed

    Naddy, Rami B; Rehner, Anita B; McNerney, Gina R; Gorsuch, Joseph W; Kramer, James R; Wood, Chris M; Paquin, Paul R; Stubblefield, William A

    2007-09-01

    The chronic (early life stage [ELS]) and short-term chronic (STC) toxicity of silver (as silver nitrate) to fathead minnows (FHM) was determined concurrently in flow-through exposures (33 volume additions/d). Paired ELS (approximately 30 d) and STC (7 d) studies were conducted with and without the addition of 60 mg/L Cl (as NaCl). The paired studies in unamended water were later repeated using standard flow conditions (9 volume additions/d). The purpose of the paired studies was to determine if short-term chronic endpoints can be used to predict effects in ELS studies. For each experiment, a "split-chamber" design (organisms were held in a common exposure chamber) allowed the direct comparison between short-term and chronic exposures. It appeared that the chronic toxicity of silver was mitigated to some extent by NaCl addition. The maximum acceptable toxicant concentration for growth in the ELS study was 0.53 microg dissolved Ag/L under standard flow conditions. Early life stage and STC endpoints in all three studies typically agreed within a factor of two. Whole-body sodium and silver concentrations measured in individual fathead minnows during these studies showed an increase in silver body burdens and a decrease in sodium concentration. These results indicate that the STC study could be used as a surrogate test to estimate chronic toxicity and that the mechanism of chronic silver toxicity may be the same as for acute toxicity.

  19. 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.

  20. 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...

  1. 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.

  2. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... loss of animals to the study (e.g., necropsy or refrigeration of those animals found dead and isolation... requirements as specified under 40 CFR part 792 subpart J, the following specific information should be... zone. (5) Particle size distribution (e.g., median aerodynamic diameter of particles with...

  3. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... loss of animals to the study (e.g., necropsy or refrigeration of those animals found dead and isolation... requirements as specified under 40 CFR part 792 subpart J, the following specific information should be... zone. (5) Particle size distribution (e.g., median aerodynamic diameter of particles with...

  4. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... loss of animals to the study (e.g., necropsy or refrigeration of those animals found dead and isolation... requirements as specified under 40 CFR part 792 subpart J, the following specific information should be... zone. (5) Particle size distribution (e.g., median aerodynamic diameter of particles with...

  5. 40 CFR 798.3260 - Chronic toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... species are used, the tester should provide justification/reasoning for their selection. (ii) Age. (A... case more than 8 weeks old. (B) Dosing of dogs should begin between 4 and 6 months of age and in no case later than 9 months of age. (C) At commencement of the study the weight variation of animals...

  6. 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

  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.

  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. Role of Folic Acid on Symptoms of Chronic Arsenic Toxicity

    PubMed Central

    Ghose, Nelima; Majumdar, Kunal Kanti; Ghose, A. K.; Saha, C. K.; Nandy, A. K.; Mazumder, D. N. Guha

    2014-01-01

    Background: Chronic arsenic toxicity (Arsenicosis) due to drinking of arsenic contaminated ground water is a global problem. However, its treatment is unsatisfactory. Methylation of arsenic facilitates its urinary excretion. Persons with relatively lower proportion of urinary dimethyl arsenic acid (DMA) are found to have at greater risk of developing symptoms of arsenicosis including its complications. The biochemical pathway responsible for methylation of arsenic is a folate-dependent pathway. Studies in rodents and humans suggest that folate nutritional status influences the metabolism of arsenic. Methods: The present study compares the effect of giving folic acid on 32 arsenicosis patients during a 6-month period and comparing the results with clinical effect of taking only arsenic-free safe water on 45 age and sex-matched arsenic-affected people for the same period. Results: There was significant improvement of arsenical skin lesion score of both patients treated with folic acid (2.96 ± 1.46 to 1.90 ± 0.90, P < 0.001) and arsenic free safe water (2.91 ± 1.26 to 1.62 ± 1.05, P < 0.001) for a period of 6 months. Significant improvement in systemic disease score was also observed from the baseline systemic score in folic acid treated group (4.78 ± 3.43 to 1.00 ± 1.56, P < 0.001) and the group treated with arsenic-free water (1.87 ± 2.11 to 0.82 ± 1.62, P < 0.001). However, there was a significant increased improvement of systematic disease score in the folic acid treated group compared to the control group taking arsenic free water (P < 0.001). Conclusions: This study provides evidence that folic acid treatment in arsenicosis cases could help in reducing clinical symptoms of arsenicosis. PMID:24554997

  12. Treating chronic arsenic toxicity with high selenium lentil diets.

    PubMed

    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 (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. 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 14weeks 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. PMID:23800687

  13. Treating chronic arsenic toxicity with high selenium lentil diets.

    PubMed

    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 (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. 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 14weeks 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.

  14. 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

  15. Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans.

    PubMed

    Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Fiumano, Vittorio; Isidori, Marina

    2014-11-01

    The growing use of cytostatic drugs is gaining relevance as an environmental concern. Environmental and distribution studies are increasing due to the development of accurate analytical methods, whereas ecotoxicological studies are still lacking. The aim of the present study was to investigate the acute and chronic toxicity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to five classes of Anatomical Therapeutic Classification (ATC) on primary consumers of the aquatic chain (Daphnia magna, Ceriodaphnia dubia, Brachionus calyciflorus, and Thamnocephalus platyurus). Acute ecotoxicological effects occurred at concentrations in the order of mgL(-)(1), higher than those predicted in the environment, and the most acutely toxic drugs among those tested were cisplatin and doxorubicin for most aquatic organisms. For chronic toxicity, cisplatin and 5-fluorouracil showed the highest toxic potential in all test organisms, inducing 50% reproduction inhibition in crustaceans at concentrations on the order of μgL(-)(1). Rotifers were less susceptible to these pharmaceuticals. On the basis of chronic results, the low effective concentrations suggest a potential environmental risk of cytostatics. Thus, this study could be an important starting point for establishing the real environmental impact of these substances.

  16. 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

  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.

  18. 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

  19. 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...

  20. 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

  1. Bull Run Fossil Plant toxicity biomonitoring study

    SciTech Connect

    Hackney, P.A.; Moses, J.

    1986-11-01

    This report presents the results of toxicity testing of the whole waste discharge from the Bull Run Steam-Electric Plant ashpond. Water chemistry tests were conducted for heavy metals content and suspended solids. Both acute and chronic toxicity tests were conducted on Daphnia pulex, Ceriodaphnia spp., Pimephales promelas, Micropterus salmoides, Lepomis macrochirus, and Cyprinus carpio. (ACR)

  2. Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

    PubMed

    Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

    2015-07-01

    After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

  3. 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

  4. Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

    PubMed

    Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

    2015-07-01

    After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver. PMID:25943488

  5. 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

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

    PubMed

    Wang, Ning; Ingersoll, Christopher G; Greer, I Eugene; Hardesty, Douglas K; Ivey, Christopher D; Kunz, James L; Brumbaugh, William G; Dwyer, F James; Roberts, Andy D; Augspurger, Tom; Kane, Cynthia M; Neves, Richard J; Barnhart, M Chris

    2007-10-01

    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 (>or=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 microg Cu/L for survival and from 4.6 to 8.5 microg 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 microg/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20 degrees 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. PMID:17867874

  7. 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.

  8. 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

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

    USGS Publications Warehouse

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

    2013-01-01

    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.

  10. A nine-year chronic toxicity study of cadmium ingestion in monkeys. I. Effects of dietary cadmium on the general health of monkeys.

    PubMed

    Masaoka, T; Akahori, F; Arai, S; Nomiyama, K; Nomiyama, H; Kobayashi, K; Nomura, Y; Suzuki, T

    1994-06-01

    Thirty-five male rhesus monkeys (Macaca mulatta) 2-5 y-of-age were separated into 5 groups and fed 200 g solid food daily which contained 0, 3, 10, 30 or 100 micrograms cadmium/g (ppm) as cadmium chloride for 462 w (9 y). The control feed (0 ppm) contained 0.27 micrograms cadmium/g. Dietary zinc intake was limited to the minimum requirement of 6 mg zinc/day (control food concentration was 3 mg zinc/100 g) to avoid impacting cadmium toxicity due to excessive zinc intake. Urine was collected at 3-w intervals. Decreased development (reduced body weight and body length) was observed in groups that received 10 ppm cadmium or more. The 100 ppm group had glucose in the urine after 48 w, elevated urine protein at 98 w, and markedly increased urine volume after the 102nd week. No abnormalities in renal functions were noted in the 3 or 10 ppm groups. Despite the development of these clinical signs of renal dysfunction, none of the 100 ppm group had aggravated renal dysfunction or renal failure during the 9 y of study.

  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.

  13. 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.

  14. 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).

  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. 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.

  17. 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

  18. 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.

  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. 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.

  1. Use of hydra for chronic toxicity assessment of waters intended for human consumption.

    PubMed

    Arkhipchuk, Victor V; Blaise, Christian; Malinovskaya, Maria V

    2006-07-01

    Methods developed with the cnidarian, Hydra attenuata (Pallas), have proven effective for screening acute toxicity in aqueous samples, whereas their use in revealing (sub)chronic toxic effects have had mitigated success. We therefore sought to explore manifestations of hydra mortality and abnormal morphological changes, as well as the reproductive capacity of hydras to further enhance the bioassay sensitivity and to assess (sub)chronic toxicity. These parameters were recorded following the onset of experiments after 8, 12 and 19-21 days of hydra exposure. Results obtained with potable waters (30 brands of bottled waters and artesian waters from 9 wells) showed chronic sublethal and lethal effects or reproduction rate inhibition for most samples. The effectiveness of the hydra toxicity test was demonstrated in comparison with other widely used bioassays. Our previous and present investigations suggest that hydra is a reliable and relevant test organism for the assessment of acute and chronic water toxicity.

  2. Acute and chronic toxicity of effluent water from an abandoned uranium mine.

    PubMed

    Antunes, S C; Pereira, R; Gonçalves, F

    2007-08-01

    Inactive or abandoned mines represent a significant source of environmental, chemical, physical, and aesthetic impact. Among concerning situations, the occurrence of abandoned or semi-abandoned mine-associated ponds (for sedimentation of solids, for effluent neutralization, or for washing the ore) is a common feature in this type of system. These ponds are a source of contamination for the groundwater resources and adjacent soils, because they lack appropriate impermeabilization. The use of this water for agriculture may also pose chronic risks to humans. In Portugal, these problems have been diagnosed and some remediation projects have been developed. The purpose of our study was to evaluate the acute and chronic toxicity of water samples collected from the aquatic system surrounding an abandoned uranium mine (Cunha Baixa, Mangualde, Central Portugal). The present study focuses on the water compartment, whose toxicity was evaluated by means of standard toxicity assays using two Daphnia species (D. longispina and D. magna). Three different ponds were used in the characterization of the aquatic system from Cunha Baixa mine: a reference pond (Ref), a mine effluent treatment pond (T), and a mine pit pond (M). Metal analyses performed in the water samples from these ponds showed values that, in some cases, were much higher than maximum recommendable values established (especially Al, Mn) by Portuguese legislation for waters for crop irrigation. Acute toxicity was only observed in the mine pit pond, with EC(50) values of 28.4% and 50.4% for D. longispina and D. magna, respectively. The significant impairment of chronic endpoints, translated in reductions in the population growth rate for both species, gives rise to concerns regarding the potential risks for aquatic zooplanktonic communities, from local receiving waters, potentially exposed to point source discharges of the treated and nontreated effluent from Cunha Baixa uranium mine.

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

    PubMed

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

    2014-09-01

    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.

  4. 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

  5. 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.

  6. 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.

  7. Optimal conditions for three brood chronic toxicity test method using a freshwater macroinvertebrate Moina macrocopa.

    PubMed

    Oh, Sorin; Choi, Kyungho

    2012-06-01

    Freshwater cladocera such as Daphnia magna and Ceriodaphnia dubia have been used extensively for freshwater toxicity test worldwide. However, these species may not be indigenous in certain geographical regions, which restrict the utility of these organisms as test species. In the present study, we investigated optimal culture and test conditions for an indigenous freshwater macroinvertebrate of Korea, Moina macrocopa. The culture conditions that were evaluated included water temperature (20°C and 25°C), rearing media (moderately hard water or MHW, with or without selenium supplementation, or Elendt M4), and food density (2.5 × 10(7) and 5 × 10(7) cells/mL of Selenastrum capricornutum), and their effects on the life history characteristics of M. macrocopa were determined. Population growth rate of M. macrocopa was maximized at 25°C with 5 × 10(7) cells/mL of algal food density in MHW. A series of chronic three brood reference toxicant tests were conducted under the ideal culture conditions that were identified here, and the results of the tests indicated reliable reproducibility of the test protocol. Optimal culture and test conditions that were identified for M. macrocopa in the present study are suggested for evaluation of chronic toxicity of chemicals and industrial or municipal discharge. PMID:21769559

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

    PubMed

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

    2013-01-01

    Irgarol 1051 has been widely used as a booster biocide in combination with copper (Cu) in antifouling paints. The combined toxicity of Irgarol with Cu on marine organisms, however, has not been fully investigated. This study investigated the acute and chronic toxicities of binary mixtures of Irgarol and CuSO(4) to the marine copepod Tigriopus japonicus. The acute combined toxicity of Irgarol and Cu was simple additive as revealed by two response surface models and their contours. However, based on chronic full life-cycle tests, when Irgarol was combined with Cu at an environmentally realistic concentration (10 μg L(-1)), a slightly synergistic effect was observed at a high Irgarol concentration (940 μg L(-1)), as shown by a significant increase in larval mortality. As Cu contamination is widespread in coastal environments, our results entail the importance of considering the combined toxic effect of the booster biocide and Cu for setting ecologically realistic water quality criteria.

  9. 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.

  10. Mechanisms of chronic waterborne Zn toxicity in Daphnia magna.

    PubMed

    Muyssen, Brita T A; De Schamphelaere, Karel A C; Janssen, Colin R

    2006-05-25

    In order to gain better insights in the integrated response of Daphnia magna following chronic zinc exposure, several physiological parameters were measured in a time-dependent manner. D. magna juveniles were exposed for 21 days to dissolved Zn concentrations up to 340 microg/L. Next to standard endpoints such as mortality, growth and reproduction the following sub-lethal endpoints were measured: filtration and ingestion rate, respiration rate, energy reserves, internal Zn and total Ca concentrations in the organisms. Organisms exposed to 80 microg/L generally performed better than the Zn deprived control organisms. The former were used to elucidate the effects of higher Zn concentrations on the endpoints mentioned above. After 1 week, only 7% of the organisms exposed to 340 microg/L survived. Body Zn contents of these organisms were 281 +/- 76 microg g dry weight and a 37% decrease of the Ca contents was observed. This suggests a competitive effect of Zn on Ca uptake. Filtration rate (-51%), individual weight (-58%) and energy reserves (-35%) also exhibited a decreasing trend as a function of increasing Zn exposure concentrations. During the second and third exposure week an overall repair process was observed. In the surviving organisms mortality and reproduction were only slightly affected. This can be explained by (over)compensation reactions at lower levels of biological organisation: Ca contents (+24%) and filtration rate (+90%) increased as a function of the exposure concentration while respiration rate decreased (-29%) resulting in energy reserves remaining constant as a function of Zn exposure. It is hypothesized that a disturbed Ca balance is probably the first cause for zinc toxicity effects in D. magna. PMID:16472524

  11. 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—...

  12. 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

  13. [Chronic toxic effects of aluminum on nervous system in rabbits].

    PubMed

    Zhang, W Q; Xu, G S; Huang, G W

    1994-05-01

    Twenty-one male rabbits were administered with alum (aluminum potassium sulfate) for 32 weeks to study the accumulative toxic effects of aluminum in food additives on central nervous system. Results showed aluminum levels in blood and brain tissue of the animals increased significantly with intake of alum (P < 0.01). Blood zinc levels, and activities of superoxide dismutase (SOD) and monoamine oxidase B (MAO-B) correlated negatively with aluminum levels in blood and brain, and SOD activity correlated negatively to accumulative aluminum deposit and positively to lipid oxide level in brain. Pathological examinations showed lesions in gyrus centralis anterior, gyrus hippocampi and spinal cord of the animals got more severely and extensively with aluminum intake and brain aluminum content, with disarrangement of neurofilaments and neurotubule, and deformation of synaptic structures.

  14. 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.

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

    PubMed

    Farag, Aïda M; Harper, David D

    2014-03-01

    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. This article is a US Government work and is in the public domain in the USA.

  16. 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.

  17. 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

  18. 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

  19. Chronic toxicity of silver nanoparticles to Daphnia magna under different feeding conditions.

    PubMed

    Mackevica, Aiga; Skjolding, Lars Michael; Gergs, Andre; Palmqvist, Annemette; Baun, Anders

    2015-04-01

    Despite substantial information on the acute toxicity of silver nanoparticles (AgNP) to aquatic organisms, little is known about their potential chronic effects and the applicability of current test guidelines for testing nanomaterials. The purpose of this study was to study the influence of food availability on toxicity. This was done through a series of Daphnia magna 21-day reproduction tests (OECD 211) using 30 nm citric acid stabilized AgNP aimed at studying the influence of food abundance on the reproductive toxicity of AgNP in D. magna. The experiments were carried out as static renewal tests with exposure concentrations from 10 to 50 μg Ag/L, and test animals were fed green algae Pseudokirchneriella subcapitata in low and high food treatments. The endpoints recorded were survival, growth of parent animals and number of live neonates produced. Detrimental effects of AgNP on survival, growth and reproduction were observed in concentrations higher than 10 μg Ag/L, whereas the animals exposed to 10 μg Ag/L had larger body length and produced more offspring than controls at both food treatments. High food treatment resulted in higher animal survival, growth and reproduction compared to result found for low food treatment. PMID:25661705

  20. 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.

  1. 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

  2. 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

  3. Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents.

    PubMed

    Mukinda, J T; Syce, J A

    2007-05-30

    Artemisia afra (Jacq. Ex. Willd), "African Wormwood" is widely used traditionally in South Africa with no literature evidence substantiating its safety. The aim of this study was to investigate the safety of the aqueous extract of Artemisia afra by determining its pharmaco-toxicological effects after acute and chronic administration in mice and rats, respectively. The aqueous extract mimicked the traditional decoction dosage form of Artemisia afra. In mice, single intraperitoneal injections of Artemisia afra-extract (1.5-5.5g/kg) induced a regular dose-dependent increase in the death rate and incidence of general behaviour adverse effects, while with single oral doses (2-24g/kg) the increases in incidence of general behaviour adverse effects and mortality rate were dose-independent. The LD(50s) after acute intraperitoneal and oral doses were 2.45 and 8.96g/kg, respectively. Rats given oral doses of Artemisia afra-extract (0.1 or 1g/kg/day) survived the 3 months of dosing (i.e. LD(50) much higher than 1g/kg), experienced no significant changes in general behaviour and haematological and biochemical parameters, except for transient decrease in AST activity. No significant changes were observed in organ weights, and histopathological results showed normal profile suggesting no morphological alterations. Collectively, the results indicate that Artemisia afra-extract is non-toxic when given acutely, has low chronic toxicity potential and, in high doses, may have a hepatoprotective effect.

  4. A comparison of mixture toxicity assessment: examining the chronic toxicity of atrazine, permethrin and chlorothalonil in mixtures to Ceriodaphnia cf. dubia.

    PubMed

    Phyu, Y L; Palmer, C G; Warne, M St J; Hose, G C; Chapman, J C; Lim, R P

    2011-11-01

    Pesticides predominantly occur in aquatic ecosystems as mixtures of varying complexity, yet relatively few studies have examined the toxicity of pesticide mixtures. Atrazine, chlorothalonil and permethrin are widely used pesticides that have different modes of action. This study examined the chronic toxicities (7-d reproductive impairment) of these pesticides in binary and ternary mixtures to the freshwater cladoceran Ceriodaphnia cf. dubia. The toxicity of the mixtures was compared to that predicted by the independent action (IA) model for mixtures, as this is the most appropriate model for chemicals with different modes of action. Following this they were compared to the toxicity predicted by the concentration addition (CA) model for mixtures. According to the IA model, the toxicity of the chlorothalonil plus atrazine mixture conformed to antagonism, while that of chlorothalonil and permethrin conformed to synergism. The toxicity of the atrazine and permethrin mixture as well as the ternary mixture conformed to IA implying there was either no interaction between the components of these mixtures and/or in the case of the ternary mixture the interactions cancelled each other out to result in IA. The synergistic and antagonistic mixtures deviated from IA by factors greater than 3 and less than 2.5, respectively. When the toxicity of the mixtures was compared to the predictions of the CA model, the binary mixture of chlorothalonil plus atrazine, permethrin plus atrazine and the ternary mixture all conformed to antagonism, while the binary mixture of chlorothalonil plus permethrin conformed to CA. Using the CA model provided estimates of mixture toxicity that did not markedly underestimate the measured toxicity, unlike the IA model, and therefore the CA model is the most suitable to use in ecological risk assessments of these pesticides.

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Acute and chronic toxicity of emerging contaminants, alone or in combination, in Chlorella vulgaris and Daphnia magna.

    PubMed

    Pablos, María Victoria; García-Hortigüela, Pilar; Fernández, Carlos

    2015-04-01

    This work presents the toxicity results of different compounds classified as emerging contaminants on primary producers and primary consumers in the aquatic compartment. The objectives were to (1) obtain acute and chronic toxicity results for algae and Daphnia magna using standardised or currently used tests, (2) study the relationship between the effects on the impaired feeding rate for daphnia and the effects of reproduction and (3) examine the responses on daphnia and algae after binary combinations of environmentally relevant compounds and perfluorooctane sulfonate (PFOS). Toxicity data on personal care products (PCPs), not reported in the scientific literature up to now, are presented. The results confirmed that the Daphnia feeding bioassay can be a sensitive, ecologically relevant endpoint to detect sublethal effects and could complement the information obtained with the reproduction test on Daphnia. The results also suggested that the concomitant occurrence of PFOS and other emerging contaminants in the aquatic compartment could affect the toxicity of some compounds according to their lipophilicity.

  11. Chronic respiratory failure due to toxic epidermal necrosis in a 10 year old girl.

    PubMed

    Thimmesch, M; Gilbert, A; Tuerlinckx, D; Bodart, E

    2015-02-01

    Toxic epidermal necrosis is a severe mucocutaneous disease with a high mortality rate. A third of the patients surviving the acute phase will develop pulmonary complications. The most frequent complication is bronchiolitis obliterans. Despite well-conducted treatment, in most cases, lung injury often leads to chronic respiratory failure. We describe here the case of a young patient that presented a toxic epidermal necrosis at the age of 3 years. Poor therapeutic compliance result in chronic respiratory failure and after 7 years of follow-up, pulmonary transplant remains the only long-term alternative. Close monitoring of respiratory symptoms in the course of toxic epidermal necrosis, intense treatment as soon as they appear and a long-term follow-up are essential to postpone chronic respiratory failure. PMID:25324191

  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. 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...

  14. 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.

  15. Effects of water chemistry on the chronic toxicity of lead to the cladoceran, Ceriodaphnia dubia.

    PubMed

    Mager, Edward M; Brix, Kevin V; Gerdes, Robert M; Ryan, Adam C; Grosell, Martin

    2011-03-01

    As the first step toward parameterization of a chronic lead (Pb) biotic ligand model (BLM) for Ceriodaphnia dubia, 7-d toxicity tests were performed in waters modified to evaluate the influences of hardness, DOM (as Suwannee River NOM and Aldrich humic acid (HA)), pH (buffered with 4 mM MOPS) and alkalinity on the chronic toxicity of Pb. Calculated EC(20)s for the control base water test and each of the most extreme modified test waters were as follows in μg L(-1) Pb (95% confidence interval): base water control=45 (14-53), 5 mM CaSO(4)=22 (12-30), 32 mg L(-1) DOM=523 (388-573), 2.5 mM NaHCO(3)=73 (21-120) and pH 6.4 buffered with MOPS=3.9 μg L(-1) Pb (1-5). Results indicate that hardness does not protect against chronic toxicity of Pb to C. dubia, whereas HA does protect at the highest concentration tested (597 μM). Additionally, our findings suggest that low pH increases the chronic toxicity of Pb whereas increased alkalinity is protective. The findings reported herein support the need for a chronic Pb BLM as an alternative approach to hardness-based regulations.

  16. 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

  17. 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

  18. Acute and sub-chronic toxicity of glucose-cysteine Maillard reaction products in Sprague-Dawley rats.

    PubMed

    Li, Yixing; Su, Linliang; Li, Fenfang; Wang, Chaozheng; Yuan, Debao; Chen, Jiao; Tan, Lin; Jin, Zhiqiang; Ma, Weihong

    2015-06-01

    Maillard reaction products (MRPs) derived from glucose-cysteine reactions have excellent anti-browning ability. However, there is a lack of information about their acute and sub-chronic toxicities. To our knowledge, the present study is the first to evaluate the acute and sub-chronic toxicities of MRPs in experimental animals. Acute toxicity testing and analysis by Horn's method showed that the median lethal oral dose (LD50) of MRPs in rats was 6.81 g/kg body weight. The sub-chronic toxicity test involved feeding rats with diet containing 0, 0.43, 0.85, or 1.70% (w/w) MRPs for 90 days. These treatments did not affect mortality, gross pathology, histology, hematology, or blood chemistry, and there were no dose-dependent changes in feed consumption. Based on these results, the dietary no-observed-adverse-effect level (NOAEL) for 90-day exposure was 1.29 and 1.51 g MRPs/kg body weight/day for male and female rats, respectively. PMID:25817020

  19. Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation.

    PubMed

    Alves, L; Paixão, S M

    2011-10-01

    The acute toxicity of some compounds used in fossil fuels biodesulphurisation studies, on the respiration activity, was evaluated by Gordonia alkanivorans and Rhodococcus erythropolis. Moreover, the effect of 2-hydroxybiphenyl on cell growth of both strains was also determined, using batch (chronic bioassays) and continuous cultures. The IC₅₀ values obtained showed the toxicity of all the compounds tested to both strains, specially the high toxicity of 2-HBP. These results were confirmed by the chronic toxicity data. The toxicity data sets highlight for a higher sensitivity to the toxicant by the strain presenting a lower growth rate, due to a lower cells number in contact with the toxicant. Thus, microorganisms exhibiting faster generation times could be more resistant to 2-HBP accumulation during a BDS process. The physiological response of both strains to 2-HBP pulse in a steady-state continuous culture shows their potential to be used in a future fossil fuel BDS process.

  20. 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

  1. 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.

  2. 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.

  3. 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.

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

    PubMed

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

    2007-08-01

    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 microg/L for Missouri sculpins and 37 microg/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 microg/L (Missouri) and 1.9 microg/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 microg/L) than Missouri sculpins (chronic ChV = 219 microg/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.

  5. Multi-linear regression analysis, preliminary biotic ligand modeling, and cross species comparison of the effects of water chemistry on chronic lead toxicity in invertebrates.

    PubMed

    Esbaugh, A J; Brix, K V; Mager, E M; De Schamphelaere, K; Grosell, M

    2012-03-01

    The current study examined the chronic toxicity of lead (Pb) to three invertebrate species: the cladoceran Ceriodaphnia dubia, the snail Lymnaea stagnalis and the rotifer Philodina rapida. The test media consisted of natural waters from across North America, varying in pertinent water chemistry parameters including dissolved organic carbon (DOC), calcium, pH and total CO(2). Chronic toxicity was assessed using reproductive endpoints for C. dubia and P. rapida while growth was assessed for L. stagnalis, with chronic toxicity varying markedly according to water chemistry. A multi-linear regression (MLR) approach was used to identify the relative importance of individual water chemistry components in predicting chronic Pb toxicity for each species. DOC was an integral component of MLR models for C. dubia and L. stagnalis, but surprisingly had no predictive impact on chronic Pb toxicity for P. rapida. Furthermore, sodium and total CO(2) were also identified as important factors affecting C. dubia toxicity; no other factors were predictive for L. stagnalis. The Pb toxicity of P. rapida was predicted by calcium and pH. The predictive power of the C. dubia and L. stagnalis MLR models was generally similar to that of the current C. dubia BLM, with R(2) values of 0.55 and 0.82 for the respective MLR models, compared to 0.45 and 0.79 for the respective BLMs. In contrast the BLM poorly predicted P. rapida toxicity (R(2)=0.19), as compared to the MLR (R(2)=0.92). The cross species variability in the effects of water chemistry, especially with respect to rotifers, suggests that cross species modeling of invertebrate chronic Pb toxicity using a C. dubia model may not always be appropriate.

  6. 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

  7. 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

  8. 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.

  9. Effects of Body-Mind Training and Relaxation Stretching on Persons with Chronic Toxic Encephalopathy.

    ERIC Educational Resources Information Center

    Engel, Lis; Andersen, Lars Bo

    2000-01-01

    Investigates the psychological and physical effects of training of body awareness and slow stretching on persons (N=8) with chronic toxic encephalopathy. Results show that electromyography on the frontalis muscle and state anxiety decreased, but no changes were observed in trait anxiety and in the creativity score. (Author/MKA)

  10. 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 ...

  11. 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,...

  12. [Pathomorphological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of a street drugs brand].

    PubMed

    Ruzin, G P; Tkachenko, O V; Miroshnichenko, M S; Pliten', O N

    2013-06-01

    In the article the authors present the pathological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of handicraft production (pervitin, vint). It is shown that this pathology is characterized by the predominance of marked degenerative, necrotic and inflammatory changes over the reparative processes.

  13. Mice fed on a diet enriched with genetically engineered multivitamin corn show no sub-acute toxic effects and no sub-chronic toxicity.

    PubMed

    Arjó, Gemma; Capell, Teresa; Matias-Guiu, Xavier; Zhu, Changfu; Christou, Paul; Piñol, Carme

    2012-12-01

    Multivitamin corn is a novel genetically engineered variety that simultaneously produces high levels of β-carotene, ascorbate and folate, and therefore has the potential to address simultaneously multiple micronutrient deficiencies caused by the lack of vitamins A, B9 and C in developing country populations. As part of the development process for genetically engineered crops and following European Food Safety Authority (EFSA) recommendations, multivitamin corn must be tested in whole food/feed sub-chronic animal feeding studies to ensure there are no adverse effects, and potential allergens must be identified. We carried out a 28-day toxicity assessment in mice, which showed no short-term sub-acute evidence of diet-related adverse health effects and no difference in clinical markers (food consumption, body weight, organ/tissue weight, haematological and biochemical blood parameters and histopathology) compared to mice fed on a control diet. A subsequent 90-day sub-chronic feeding study again showed no indications of toxicity compared to mice fed on control diets. Our data confirm that diets enriched with multivitamin corn have no adverse effects on mice, do not induce any clinical signs of toxicity and do not contain known allergens.

  14. Sporadic mortality in chronic toxicity tests using Pimephales promelas (Rafinesque): Cases of characterization and control

    SciTech Connect

    Downey, P.J.; Fleming, K.; Guinn, R.; Chapman, N.; Varner, P.; Cooney, J.D.

    2000-01-01

    In whole effluent toxicity tests, organisms are exposed to various effluent concentrations for a specific time period to estimate the potential effects of an effluent on a receiving stream. Laboratories typically have good success performing valid chronic toxicity tests. However, some difficulty in conducting valid chronic whole effluent toxicity tests with Pimephales promelas (fathead minnow) has been encountered as a result of sporadic control mortality. Some investigators report an interference that causes anomalous patterns of survival in chronic fathead minnow tests. This interference has been termed sporadic mortality phenomenon. Characteristics of sporadic mortality phenomenon include high variability among replicates, nonmonotonic dose responses, mortality beginning on or about day 4 of the test, and fungal growths often observed on the larvae. Histopathologic examinations often indicate bacterial and/or fungal infections on fish exhibiting symptoms of sporadic mortality phenomenon. The most plausible explanation of sporadic mortality phenomenon is a naturally occurring pathogen or pathogens that interfere with the test method. This interference may invalidate tests or falsely indicate toxicity. Sporadic mortality phenomenon can be reduced or eliminated by sample treatments intended to inactivate (heating, antibiotics, or ultraviolet light) or remove (filtration) pathogenic microorganisms. These methods must be used with forethought because of their potential to alter the toxicity of a sample.

  15. 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

  16. Bioavailability and chronic toxicity of cadmium in sediment to the estuarine amphipod Leptocheirus plumulosus

    SciTech Connect

    DeWitt, T.H.; Swartz, R.C.; Hansen, D.J.; McGovern, D.; Berry, W.J.

    1996-12-01

    Numerous studies have demonstrated the efficacy of interstitial water metal concentrations and simultaneously extracted metals/acid-volatile sulfide (SEM/AVS) ratios in explaining the acute toxicity of sediment-associated metals to benthic organisms. However, no full life-cycle chronic marine or estuarine tests have been conducted for this purpose. In this study, cohorts of newborn amphipods, Leptocheirus plumulosus, were exposed to cadmium-spiked estuarine sediment for 28 d to determine effects on mortality, growth, and reproduction relative to interstitial water and SEM/AVS normalization. Seven treatments of cadmium were tested: 0 (control), 0.34, 0.74, 1.31, 1.55, 2.23, and 4.82 M SEM{sub Cd}/AVS ratios (measured concentrations). Interstitial water cadmium (IW{sub Cd}) and sediment concentrations of SEM{sub Cd} and AVS were monitored periodically and by depth during the exposure. When sediment SEM{sub Cd}/AVS ratios were {le} 1.55, mean IW{sub Cd} concentrations were less than the 96-h water-only cadmium LC50 for juvenile and subadult L. plumulosus, and mortality, growth, and reproduction were not affected. When SEM{sub Cd}/AVD ratios were {ge} 2.23, IW{sub Cd} concentrations were more than 100 times greater than the 96-h water-only cadmium LC50, and all amphipods died. These results are consistent with predictions of metal bioavailability from acute tests with metal-spiked sediments, i.e., that sediments with SEM{sub Cd}/AVS ratios < 1 are not toxic, while sediments with SEM{sub Cd}/AVS ratios > 1 may be toxic.

  17. 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

  18. 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.

  19. 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.

    2016-01-01

    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.

  20. 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.

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

    PubMed

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

    2016-01-01

    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 1 mg K/L to 3 mg 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.

  2. 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

  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 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.

  5. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... animal studies. EPA has proposed guidelines for assessing female reproductive risk but has not yet proposed a specific system for categorization of female reproductive toxicants. (i) Known Human Female... “Probable Human Male Reproductive Toxicant.” (4) Female Reproductive Toxicants. Female...

  6. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... animal studies. EPA has proposed guidelines for assessing female reproductive risk but has not yet proposed a specific system for categorization of female reproductive toxicants. (i) Known Human Female... “Probable Human Male Reproductive Toxicant.” (4) Female Reproductive Toxicants. Female...

  7. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... animal studies. EPA has proposed guidelines for assessing female reproductive risk but has not yet proposed a specific system for categorization of female reproductive toxicants. (i) Known Human Female... “Probable Human Male Reproductive Toxicant.” (4) Female Reproductive Toxicants. Female...

  8. 16 CFR 1500.135 - Summary of guidelines for determining chronic toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... animal studies. EPA has proposed guidelines for assessing female reproductive risk but has not yet proposed a specific system for categorization of female reproductive toxicants. (i) Known Human Female... “Probable Human Male Reproductive Toxicant.” (4) Female Reproductive Toxicants. Female...

  9. Development of a water quality criterion for chronic toxicity using an alternative measure of the NOEL

    SciTech Connect

    Fikslin, T.

    1995-12-31

    The use of the NOEL (No Effect Level) to determine safe concentrations of toxic substances has recently been questioned since the NOEL is generally estimated using hypothesis testing procedures, and is significantly affected by several test variables. An alternative approach involved the selection of a benchmark effect level and a statistical procedure to estimate the effluent concentration which would result in a fixed reduction of 10% in the growth of the fathead minnow, Pimephales promelas, or the reproduction of the cladoceran, Ceriodaphnia. Tests conducted on ambient samples and samples from 50 industrial and municipal effluents discharging to the tidal Delaware River were utilized to derive EC10 and NOEL values for each test. 72% of the ratios of the EC10 to NOEL values were less than or equal to 1.0 indicating that the NOEL determined using hypothesis testing procedures frequently exceeded a concentration which produces a 10% reduction in the response of test organisms compared to control organisms. A water quality criterion for chronic toxicity was developed using these results by calculating the goth percentile of the cumulative frequency distribution of the ratios. This procedure is similar to the one used by the US Environmental Protection Agency to develop the acute toxicity criterion of 0.3 Toxic Units. A 90th percentile value of 0.47 was calculated for this data set. A water quality criterion of 0.5 Toxic Units for chronic toxicity to aquatic life in the tidal Delaware River would therefore represent a more consistent and acceptable level of chronic toxicity based upon a fixed and minimal impairment in growth and reproduction.

  10. Chronic toxicity of a laundry detergent to the freshwater flagellate Euglena gracilis.

    PubMed

    Azizullah, Azizullah; Richter, Peter; Jamil, Muhammad; Häder, Donat-Peter

    2012-10-01

    Chronic toxicity of the common laundry detergent Ariel on the freshwater alga Euglena gracilis was investigated by growing the alga in a medium containing the detergent for 7 days. Cell density, motility, swimming velocity, gravitactic orientation, cell shape, photosynthesis and concentration of light-harvesting pigments were used as end point parameters for the assessment of toxicity. Cell density was significantly reduced at a concentration of 1 mg l(-1) or above. Among the other tested parameters, with the exception of cell shape, gravitaxis and chlorophyll b, all were adversely affected by the detergent at concentrations exceeding 1 mg l(-1). It is concluded that long-term (7-days) exposure to the detergent caused significant toxicity to E. gracilis. Furthermore, long-term tests with E. gracilis can be used as sensitive indicator for the toxicity assessment of laundry detergents in aquatic environments.

  11. Effect of an acute and chronic toxicity of four commercial detergents on the freshwater fish Gambusia affinis Baird & Gerard.

    PubMed

    Saxena, Pratibha; Sharma, Subhasini; Sharma, Shweta; Suryavathi, V; Grover, Ruby; Soni, Pratima; Kumar, Suresh; Sharma, K P

    2005-04-01

    The toxic effects of four commercial detergents (two washing powders and two cakes) are reported in this paper on behavior, mortality and RBC counts of a freshwater fish Gambusia affinis. During acute toxicity studies (96h), surface movements of fish increased markedly for 24h, only at higher concentrations (>10 ppm) of all the four detergents. Thereafter, they were lethargic and bottom dwellers similar to those exposed for a period of 30 days in the longterm ecotoxicological studies made on detergent powders at a sublethal concentration (10 ppm). The detergents exposed to fish were found slippery due to mucous secretion. Hemorrhage regions were also found on their gills. The dissolved oxygen content also decreased (10-18%) in the detergent treatments of higher concentration (> 10 ppm). During acute toxicity studies, cakes (LC50 = 6.69 - 19.98ppm) were found more toxic than powders (LC50 = 18.34-20.72ppm). In comparison to the control fish, RBC counts decreased (12-64%) in the detergent exposed fish, being more pronounced among those exposed to cakes. The chronic exposure (30 days) of the fish also resulted in reduction in the RBC counts (41-58%). It is thus evident that all the four detergents are toxic to the fish Gambusia affinis.

  12. 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

  13. The effect of chronic toxicity of pethidine on the spinal cord: an experimental model in rabbits.

    PubMed

    Peştean, C; Taulescu, M; Ober, C; Cătoi, C; Miclăuş, V; Oana, L; Bodolea, C

    2013-01-01

    The aim of this study was to evaluate the toxicity of chronic spinal analgesia with pethidine in a rabbit model. We introduced epidural catheters in twenty New Zealand white rabbits, divided into two groups, and we administered 0.5 mg/kg pethidine or the same volume of normal saline through the catheters, for three consecutive days. Throughout the experiment, the animals were evaluated in terms of neurological status using the Tarlov score. After the rabbit's euthanasia, 4 μm sections of spinal cord stained with Hematoxylin-Eosin were analyzed by a pathologist blinded to the study for neurohistopathological changes. The results were statistically analyzed with Prism 5 software for Windows. No significant differences were noticed between the two groups in as far as body temperature (p=0.295) and weight (p=0.139) were concerned. In the group of animals, which received epidural pethidine, nine rabbits showed histological changes suggestive for neurotoxicity at the lumbar level of the spinal cord. These findings were significantly different compared with the control group which received only saline (no microscopic lesions revealed; p=0.0006). When combining the data from both groups or using the pethidine group alone, there was a significant correlation between the presence of neurological injury (Tarlov score) and the presence of the histopathological lesions in the spinal cord (r=-0.709, p=0.0002 and r=-0.635, p=0.013, respectively). Based on our findings, the chronic epidural administration of pethidine in rabbits induces moderate to severe histological changes on the spinal cord, but further investigations are needed to make a definitive statement about the histological effect of pethidine on the neurological tissue. PMID:24068413

  14. Acute and chronic toxicity of atrazine and its metabolites deethylatrazine and deisopropylatrazine on aquatic organisms.

    PubMed

    Ralston-Hooper, Kimberly; Hardy, Jeff; Hahn, Leighanne; Ochoa-Acuña, Hugo; Lee, Linda S; Mollenhauer, Robert; Sepúlveda, Maria S

    2009-10-01

    Little is known about the toxicity of the atrazine (ATRZ) metabolites desethylatrazine (DEA) and deisopropylatrazine (DIA). We evaluated the acute and chronic toxicity of ATRZ, DEA, and DIA on the amphipods Hyalella azteca and Diporeia spp., and the unicellular algae Pseudokirchneriella subcapitata. In general, acute and chronic toxicity was ranked ATRZ > DEA > DIA. All 96-h median inhibition concentrations (IC(50)) were above concentrations found in the environment (>1,500 microg/L), and sensitivity was highest for the algae. When amphipods were exposed chronically (21 days), Diporeia was several orders of magnitude more sensitive compared to H. azteca. Neither ATRZ nor DEA altered H. azteca sex ratios. In conclusion, our results suggest that short-term exposures of these chemicals to algae and amphipods to concentrations routinely detected in surface waters are unlikely to be a cause of concern. However, the unexpected high sensitivity of Diporeia spp. to these herbicides deserves further attention considering the declining status of this amphipod in the Great Lakes basin.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  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. 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.

  2. Chronic arsenic toxicity in west Bengal--the worst calamity in the world.

    PubMed

    Mazumder, D N; Das Gupta, J; Santra, A; Pal, A; Ghose, A; Sarkar, S

    1998-01-01

    Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.

  3. Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol--I. Introduction, experimental design, and aerosol generation methods.

    PubMed

    Ulrich, C E; Rinehart, W; Busey, W

    1979-03-01

    A brief literature review on manganese toxicity is presented; as related to designing a chronic inhalation study for evaluating methylcyclopentadienyl manganese tricarbonyl when utilized as a motor fuel additive. The experimental design of this study is described. The generation system utilized to simulate the manganese aerosol produced by an internal combustion engine is described in detail. This generation system operated twenty-four hours per day, seven days per week producing aerosols at 11.6, 112.5, and 1152 micrograms Mn/m3 with an aerodynamic diameter of approximately 0.11 micron.

  4. 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

  5. Comparative toxicity assessment of nanosilver on three Daphnia species in acute, chronic and multi-generation experiments.

    PubMed

    Völker, Carolin; Boedicker, Cathinka; Daubenthaler, Jan; Oetken, Matthias; Oehlmann, Jörg

    2013-01-01

    The antibacterial properties of nanosilver have led to a versatile application spectrum including medical purposes and personal care products. However, the increasing use of nanosilver has raised concerns about its environmental impacts. Long-term exposure studies with aquatic invertebrates are essential to assess possible adverse effects on aquatic ecosystems. In the present study, acute (48 h), chronic (21 d) and long-term effects of nanosilver (primary size 15 nm) on five successive generations of three Daphnia species (D. magna, D. pulex, and D. galeata) were investigated. Acute EC50 values of nanosilver were 121 µg Ag L(-1) for D. magna being the least sensitive species and 8.95 and 13.9 µg Ag L(-1) for D. pulex and D. galeata, respectively. Chronic exposure provided EC10 values of 0.92 µg Ag L(-1) for D. magna showing the most sensitive chronic reaction and 2.25 and 3.45 µg Ag L(-1) for D. pulex and D. galeata, respectively. Comparative exposure to AgNO3 revealed a generally higher toxicity of the soluble form of silver. The multi-generation experiments resulted in effects on the population level for all tested species. Exposure of D. magna indicated an increased toxicity of nanosilver in the fifth generation of animals exposed to 10 µg Ag L(-1). Neonates from pre-exposed parental daphnids did not completely recover when transferred into clean water. Exposure of D. pulex and D. galeata revealed not only increasing toxicity in some generations, but also greater tolerance to nanosilver. This study contributes to the assessment of the risk potential of nanosilver on aquatic ecosystems. It shows that effects of nanosilver vary within one genus and change with exposure duration. Therefore, long-term studies considering different aquatic species are needed to better understand the possible effects of nanosilver on aquatic ecosystems.

  6. Comparative Toxicity Assessment of Nanosilver on Three Daphnia Species in Acute, Chronic and Multi-Generation Experiments

    PubMed Central

    Völker, Carolin; Boedicker, Cathinka; Daubenthaler, Jan; Oetken, Matthias; Oehlmann, Jörg

    2013-01-01

    The antibacterial properties of nanosilver have led to a versatile application spectrum including medical purposes and personal care products. However, the increasing use of nanosilver has raised concerns about its environmental impacts. Long-term exposure studies with aquatic invertebrates are essential to assess possible adverse effects on aquatic ecosystems. In the present study, acute (48 h), chronic (21 d) and long-term effects of nanosilver (primary size 15 nm) on five successive generations of three Daphnia species (D. magna, D. pulex, and D. galeata) were investigated. Acute EC50 values of nanosilver were 121 µg Ag L−1 for D. magna being the least sensitive species and 8.95 and 13.9 µg Ag L−1 for D. pulex and D. galeata, respectively. Chronic exposure provided EC10 values of 0.92 µg Ag L−1 for D. magna showing the most sensitive chronic reaction and 2.25 and 3.45 µg Ag L−1 for D. pulex and D. galeata, respectively. Comparative exposure to AgNO3 revealed a generally higher toxicity of the soluble form of silver. The multi-generation experiments resulted in effects on the population level for all tested species. Exposure of D. magna indicated an increased toxicity of nanosilver in the fifth generation of animals exposed to 10 µg Ag L−1. Neonates from pre-exposed parental daphnids did not completely recover when transferred into clean water. Exposure of D. pulex and D. galeata revealed not only increasing toxicity in some generations, but also greater tolerance to nanosilver. This study contributes to the assessment of the risk potential of nanosilver on aquatic ecosystems. It shows that effects of nanosilver vary within one genus and change with exposure duration. Therefore, long-term studies considering different aquatic species are needed to better understand the possible effects of nanosilver on aquatic ecosystems. PMID:24116021

  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. Impact of aluminum sub-chronic toxicity on body weight and recognition memory of wistar rat.

    PubMed

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2008-07-15

    The aims of this study was to investigate the impact of aluminum nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain aluminum accumulation and especially in recognition memory of wistar rats. Two groups of young female wistar rats were used. Treated rats received (80 mg L(-1)) of aluminum nitrate diluted in drinking water, while control rats received a drinking water only, for 3 months. An evolution of body weight, a motor activity, object recognition memory (NOR) and brain aluminum concentration has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the open field test and to the novel object recognizing memory test. The results have showed a significant decrease in rats' body weight (p < 0.05). Though, no significance was registered for motor activity. Nevertheless, a high significance is showed for recognition memory compared to control rats (p < 0.01), especially at the end of testing period, even the difference between control and aluminium treated rats in brain aluminum levels was not significant.

  9. Impact of lead sub-chronic toxicity on recognition memory and motor activity of Wistar rat.

    PubMed

    Azzaoui, F Z; Ahami, A O T; Khadmaoui, A

    2009-01-15

    The aim of this research was to investigate the impact of lead nitrate administered in drinking water during 90 days (sub-chronic toxicity), on body weight gain, motor activity, brain lead accumulation and especially on recognition memory of Wistar rats. Two groups of young female Wistar rats were used. Treated rats received 20 mg L(-1) of lead nitrate diluted in drinking water, while control rats received drinking water only, for 3 months. An evolution of body weight, motor activity, object recognition memory and measure of brain lead levels has been evaluated. The body weight was taken weekly, whereas the memory abilities and the motor activity are measured once every fortnight alternatively, by submitting rats to the Open Field (OF) test and to the Novel Object Recognizing (NOR) memory test. The results have shown a non significant effect in gain of body weight. However, a high significance was shown for horizontal activity (p<0.01), long memory term (p<0.01), at the end of testing period and for brain lead levels (p<0.05) between studied groups.

  10. The chronic toxicity of molybdate to freshwater organisms. I. Generating reliable effects data.

    PubMed

    De Schamphelaere, K A C; Stubblefield, W; Rodriguez, P; Vleminckx, K; Janssen, C R

    2010-10-15

    The European Union regulation on Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) (EC, 2006) requires the characterization of the chronic toxicity of many chemicals in the aquatic environment, including molybdate (MoO(4)(2-)). Our literature review on the ecotoxicity of molybdate revealed that a limited amount of reliable chronic no observed effect concentrations (NOECs) for the derivation of a predicted no-effect concentration (PNEC) existed. This paper presents the results of additional ecotoxicity experiments that were conducted in order to fulfill the requirements for the derivation of a PNEC by means of the scientifically most robust species sensitivity distribution (SSD) approach (also called the statistical extrapolation approach). Ten test species were chronically exposed to molybdate (added as sodium molybdate dihydrate, Na(2)MoO(4)·2H(2)O) according to internationally accepted standard testing guidelines or equivalent. The 10% effective concentrations (EC10, expressed as measured dissolved molybdenum) for the most sensitive endpoint per species were 62.8-105.6 (mg Mo)/L for Daphnia magna (21day-reproduction), 78.2 (mg Mo)/L for Ceriodaphnia dubia (7day-reproduction), 61.2-366.2 (mg Mo)/L for the green alga Pseudokirchneriella subcapitata (72h-growth rate), 193.6 (mg Mo)/L for the rotifer Brachionus calyciflorus (48h-population growth rate), 121.4 (mg Mo)/L for the midge Chironomus riparius (14day-growth), 211.3 (mg Mo)/L for the snail Lymnaea stagnalis (28day-growth rate), 115.9 (mg Mo)/L for the frog Xenopus laevis (4day-larval development), 241.5 (mg Mo)/L for the higher plant Lemna minor (7day-growth rate), 39.3 (mg Mo)/L for the fathead minnow Pimephales promelas (34day-dry weight/biomass), and 43.2 (mg Mo)/L for the rainbow trout Oncorhynchus mykiss (78day-biomass). These effect concentrations are in line with the few reliable data currently available in the open literature. The data presented in this study can

  11. Toxicity effects of hazardous and noxious substances (HNS) to marine organisms: acute and chronic toxicity of p-xylene to the amphipod Gammarus locusta.

    PubMed

    Neuparth, T; Capela, R; Pereira, S P P; Moreira, S M; Santos, M M; Reis-Henriques, M A

    2014-01-01

    Despite the recent focus on hazardous and noxious substances (HNS) spills preparedness and responses, much remains to be done regarding the threat posed by HNS spills on marine biota. Among the identified priority HNS, p-xylene was selected to conduct ecotoxicological assays. The aim of this study was to assess the performance of the amphipod Gammarus locusta under acute and chronic exposure to p-xylene simulating conditions of a spill incident. In the acute exposure (96 h) the p-xylene LC50 was estimated. In the chronic bioassay (36 d), an integration of organism-level endpoints (survival, growth rate, and sex ratio) with biochemical markers indicative of oxidative stress including catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD) activities and lipid peroxidation (LPO) levels was determined. The aim was to increase the xylene ecotoxicological database and better predict its impact in aquatic environments. p-Xylene induced several chronic toxicity effects in G. locusta. Significant alterations in antioxidant enzymes and lipid peroxidation levels as well as growth rate and biased sex-ratio were observed. p-Xylene significantly affected the activities of CAT, SOD, and GST in G. locusta and produced oxidative damage by increasing levels of LPO in males. Further, impacts in key ecological endpoints, that is, growth and sex ratio, were noted that might be indicative of potential effects at the population level in a spill scenario. The present data may be useful to assist relevant bodies in preparedness and response to HNS spills. PMID:25208661

  12. Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

    PubMed

    Rahman, M M; Chowdhury, U K; Mukherjee, S C; Mondal, B K; Paul, K; Lodh, D; Biswas, B K; Chanda, C R; Basu, G K; Saha, K C; Roy, S; Das, R; Palit, S K; Quamruzzaman, Q; Chakraborti, D

    2001-01-01

    Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement

  13. 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.

  14. 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

  15. 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.

  16. Chronic toxicity of heavy fuel oils to fish embryos using multiple exposure scenarios.

    PubMed

    Martin, Jonathan D; Adams, Julie; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

    2014-03-01

    The chronic toxicity to rainbow trout (Oncorhynchus mykiss) embryos of heavy fuel oil (HFO) 6303, weathered HFO 6303, HFO 7102, and medium South American (MESA) crude oil was assessed by different exposure regimes. These included water accommodated fractions (WAF; water in contact with floating oil), chemically enhanced WAF (CEWAF; oil dispersed with Corexit 9500), and effluent from columns of gravel coated with stranded oil. Heavy fuel oil WAF was nontoxic and did not contain detectable concentrations of hydrocarbons, likely because the high density and viscosity of HFO prevented droplet formation. In contrast, chemically dispersed HFO and effluent from columns of stranded HFO contained measurable concentrations of alkyl polycyclic aromatic hydrocarbons (PAH), coincident with embryo toxicity. These exposure regimes enhanced the surface area of oil in contact with water, facilitating oil-water partitioning of hydrocarbons. Heavy fuel oil was consistently more toxic to fish than crude oil and the rank order of alkyl PAH concentrations in whole oil were sufficient to explain the rank order of toxicity, regardless of exposure method. Thus, the propensity of HFO to sink and strand in spawning shoals creates a long-term risk to developing fish because of the sustained release of PAHs from HFO to interstitial waters. Further, PAH monitoring is key to accurate risk assessment.

  17. 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

  18. Acute and chronic cadmium toxicity to a saltwater cladoceran Moina monogolica Daday and its relative importance.

    PubMed

    Wang, Zaosheng; Yan, Changzhou; Zhang, Xian

    2009-01-01

    Acute and chronic toxicity tests of a saltwater cladoceran Moina monogolica Daday exposed to cadmium were conducted according to the American Society for Testing and Materials (ASTM) guidelines. The 24- and 48-h LC50s and their 95% confidence intervals (CIs) were calculated as 9.59 (8.91-10.26) and 1.87 (1.46-2.32) mg Cd/l, respectively, based on measured cadmium concentrations. When compared with different phyla or classes of saltwater animals, M. monogolica had moderate sensitivity and was suitable to be used as an indicator organism. Eight end points used to evaluate chronic effects were affected at chronic cadmium concentrations. Test organisms ceased to reproduce when exposed to equal to or greater than 308.10 microg Cd/l. Comparisons of chronic effects showed that mechanisms of metal accumulation patterns M. monogolica exposed to cadmium are different from those of dissolved copper exposure. The point estimates using linear regression equations of net reproductive rate generated the maximum-acceptable-toxicant concentration of 1.78 microg Cd/l, the lowest-observed-effect concentration of 3.01 microg Cd/l and the no-observed-effect concentration of 1.11 microg Cd/l. Comparisons among thresholds, cadmium concentrations in natural aquatic systems and water quality criteria showed that aquatic organisms were possibly negatively affected at some sites of higher cadmium concentrations. Further research is needed to focus on risk assessment of cadmium on saltwater aquatic organisms and water quality criteria development of China. PMID:18719993

  19. Chronic arsenic toxicity: clinical features, epidemiology, and treatment: experience in West Bengal.

    PubMed

    Guha Mazumder, D N

    2003-01-01

    Chronic arsenic toxicity due to drinking arsenic-contaminated water has been one of the worst environmental health hazards affecting eight districts of West Bengal since the early eighties. Detailed clinical examination and investigation of 248 such patients revealed protean clinical manifestations of such toxicity. Over and above hyperpigmentation and keratosis, weakness, anaemia, burning sensation of eyes, solid swelling of legs, liver fibrosis, chronic lung disease, gangrene of toes, neuropathy, and skin cancer are some of the other manifestations. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. Out of a population of 7683 surveyed, 3467 and 4216 people consumed water containing As below and above 0.05 mg/L, respectively. Except pain abdomen the prevalence of all other clinical manifestations tested (e.g., pigmentation, keratosis, hepatomegaly, weakness, nausea, lung disease and neuropathy) were found to be significantly higher in As exposed people (water As > 0.05 mg/L) compared to control population (water As level < 0.05 mg/L). The prevalence of pigmentation and keratosis, hepatomegaly, chronic respiratory disease and weakness rose significantly with increasing arsenic concentrations in drinking water. The respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesion. Therapy with chelating agent DMSA was not found to be superior to placebo effect. However, therapy with DMPS caused significant improvement of clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90 +/- 2.84 to 3.27 +/- 1.73; p < 0.0001. Efficacy of specific chelation therapy for patients suffering from chronic As toxicity has further need to be fully substantiated. However, supportive treatment could help in reducing many symptoms of the patients. Treatment in hospital with

  20. Evidence of antiapoptotic properties of Pleurotus florida lectin against chronic arsenic toxicity in renal cells of rats.

    PubMed

    Rana, Tanmoy; Bera, Asit Kumar; Bhattacharya, Debasis; Das, Subhashree; Pan, Diganta; Das, Subrata Kumar

    2012-01-01

    Chronic arsenic exposure results in toxicity in humans and causes many toxicologic manifestations. Apoptosis was measured by cell adhesion, morphologic alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL), and caspase-3/CPP32 fluorometric protease assay. Results of the present study suggested that arsenic administration in rats caused apoptosis by elevating morphologic alterations, TUNEL-positive nuclei, caspase-3 activity, and DNA damage and by reducing cell adhesion and cell proliferation in a time-dependent manner. The apoptosis in renal cells of arsenic-exposed rats reverted to normal values after coadministration of mushroom lectin. This study provided significant evidence that Pleurotus florida lectin has an antiapoptotic property by protecting from arsenic-induced toxicity. The beneficial effect of Pleurotus florida lectin was proportional to its duration of exposure. This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent. PMID:22591283

  1. Evidence of antiapoptotic properties of Pleurotus florida lectin against chronic arsenic toxicity in renal cells of rats.

    PubMed

    Rana, Tanmoy; Bera, Asit Kumar; Bhattacharya, Debasis; Das, Subhashree; Pan, Diganta; Das, Subrata Kumar

    2012-01-01

    Chronic arsenic exposure results in toxicity in humans and causes many toxicologic manifestations. Apoptosis was measured by cell adhesion, morphologic alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL), and caspase-3/CPP32 fluorometric protease assay. Results of the present study suggested that arsenic administration in rats caused apoptosis by elevating morphologic alterations, TUNEL-positive nuclei, caspase-3 activity, and DNA damage and by reducing cell adhesion and cell proliferation in a time-dependent manner. The apoptosis in renal cells of arsenic-exposed rats reverted to normal values after coadministration of mushroom lectin. This study provided significant evidence that Pleurotus florida lectin has an antiapoptotic property by protecting from arsenic-induced toxicity. The beneficial effect of Pleurotus florida lectin was proportional to its duration of exposure. This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent.

  2. 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.

  3. 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

  4. Accumulation and chronic toxicity of uranium over different life stages of the aquatic invertebrate Chironomus tentans.

    PubMed

    Muscatello, Jorgelina R; Liber, Karsten

    2009-10-01

    Limited data are available on the effects of uranium (U) exposures on benthic macroinvertebrates, something that would be needed before national or provincial water quality guidelines could be developed. The goal of this study was to evaluate chronic U toxicity and accumulation in the aquatic invertebrate Chironomus tentans. Test organisms were exposed to three aqueous U concentrations (40, 200, and 1,000 microg/L) and an untreated control. Larval growth, adult emergence, and U tissue concentrations at different life stages were evaluated. The measured no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) for growth of C. tentans larvae after 10 days of U exposure were 39 and 157 microg/L, respectively. At U concentrations >157 ug/L, there was reduced larval growth of 30% to 40%, which corresponded to reduced adult emergence of 40% to 60%. Despite significant delays in time to adult emergence, there were no significant effects on reproductive output of successfully emerged adults. The F(1) generation C. tentans larvae that were never directly exposed to U, but originated from adult males and females exposed to U during their immature life stages, displayed a significant decrease in 10-day growth that was similar to that observed for the F(0)-exposed larvae. This suggests that the environment of the parental generation can significantly influence the development of the next generation through environmentally induced parental effects. Uranium accumulated in C. tentans immature stages was partially excreted during molting and metamorphosis to the adult stage. However, the elimination of U was not complete and some was still measured in adult midges. Consequently, a minor transfer of U from the aquatic to the terrestrial environment could be expected to occur.

  5. 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.

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

    PubMed

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

    1982-03-01

    Acute injections of high doses of Cd induce 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 contributions 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 sacrificed 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 significant 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.

  7. Cerebrospinal fluid proteins and free amino acids in patients with solvent induced chronic toxic encephalopathy and healthy controls.

    PubMed Central

    Moen, B E; Kyvik, K R; Engelsen, B A; Riise, T

    1990-01-01

    The concentrations of protein, albumin, IgG, and free amino acids in the cerebrospinal fluid of 16 patients with chronic toxic encephalopathy due to organic solvents were measured. The patient group consisted of all patients with this diagnosis in a neurological department in 1985. The diagnosis was based on neuraesthenic symptoms, pathological psychometric performance, and verified exposure to neurotoxic organic solvents. A control group of 16 patients with myalgias or backache, or both, and no signs of disease was used for comparison. The purpose was to study possible changes in the cerebrospinal fluid that might contribute to understanding the aetiology of solvent induced chronic toxic encephalopathy. A rise in protein, albumin, and IgG was found in the patient group compared with the control group, as well as reduced concentrations of phosphoethanolamine, taurine, homocarnosine, ethanolamine, alpha-aminobutyric acid, and leucine. Using a stepwise multiple regression analysis, taurine was negatively correlated to exposure to solvents. These findings may indicate membrane alterations in the central nervous system related to exposure to organic solvents. PMID:2337535

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Alzheimer's disease and methanol toxicity (part 1): chronic methanol feeding led to memory impairments and tau hyperphosphorylation in mice.

    PubMed

    Yang, Meifeng; Lu, Jing; Miao, Junye; Rizak, Joshua; Yang, Jianzhen; Zhai, Rongwei; Zhou, Jun; Qu, Jiagui; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Hu, Xintian; He, Rongqiao

    2014-01-01

    Although methanol toxicity is well known for acute neurological sequelae leading to blindness or death, there is a new impetus to investigate the chronic effects of methanol exposure. These include a recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology. In the present study, mice were fed with methanol to revisit the chronic effects of methanol toxicity, especially as it pertains to AD progression. Three groups of mice (n = 9) were given either water as a control or a methanol solution (concentrations of 2% or 3.8%) over a 6-week period. The methanol-fed mice were found to have impaired spatial recognition and olfactory memory in Y-maze and olfactory memory paradigms. Immunohistochemical analysis of the mouse brains found increased neuronal tau phosphorylation in the hippocampus and an increased cellular apoptotic marker in hippocampal CA1 neurons (~10% of neurons displayed chromatin condensation) in the methanol-fed groups. Two additional in vitro experiments in mouse embryonic cerebral cortex neurons and mouse neuroblastoma N2a cells found that formaldehyde, but not methanol or the methanol end product formic acid, induced microtubule disintegration and tau protein hyperphosphorylation. The findings of the behavioral tests and immunohistochemical analysis suggested that the methanol-fed mice presented with partial AD-like symptoms. The in vitro experiments suggested that formaldehyde was most likely the detrimental component of methanol toxicity related to hippocampal tau phosphorylation and the subsequent impaired memory in the mice. These findings add to a growing body of evidence that links formaldehyde to AD pathology.

  14. 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

  15. 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.

  16. 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...

  17. Subchronic toxicity study of GH transgenic carp.

    PubMed

    Yong, Ling; Liu, Yu-Mei; Jia, Xu-Dong; Li, Ning; Zhang, Wen-Zhong

    2012-11-01

    A subchronic toxicity study of GH (growth hormone) transgenic carp was carried out with 60 SD rats aged 4 weeks, weight 115∼125 g. Ten male and 10 female rats were allotted into each group. Animals of the three groups (transgenic carp group (GH-TC), parental carp group (PC) and control group) were fed soy- and alfalfa-free diet (SAFD) with 10% GH transgenic carp powder, 10% parental carp powder or 10% common carp powder for 90 consecutive days, respectively. In the end of study, animals were killed by exsanguination via the carotid artery under diethyl ether anesthesia, then weights of heart, liver, kidneys, spleen, thymus, brain, ovaries and uterus/testis were measured. Pathological examination of organs was determined. Endocrine hormones of triiodothyronine (T3), thyroid hormone (T4), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone (P) and testosterone (T) levels were detected by specific ELISA kit. Parameters of blood routine and blood biochemical were measured. The weights of the body and organs of the rats, food intake, blood routine, blood biochemical test and serum hormones showed no significant differences among the GH transgenic carp-treated, parental carp-treated and control groups (P>0.05). Thus, it was concluded that at the dose level of this study, GH transgenic carp showed no subchronic toxicity and endocrine disruption to SD rats.

  18. Toxicological studies on aquatic contaminants originating from coal production and utilization: the induction of tolerance to silver in laboratory populations of fish and the chronic toxicity of nickel to fish early-life stages. Research report July 1983-August 1984

    SciTech Connect

    Birge, W.J.; Black, J.A.; Hobson, J.F.; Westerman, A.G.; Short, T.M.

    1984-08-01

    Aquatic toxicity studies were performed on two important coal-derived contaminants, silver and nickel. Silver was investigated with regard to metal-induced tolerance in laboratory populations of the fathead minnow (Pimephales promelas). Fish were exposed to acute silver concentrations following acclimation to sublethal exposures of this metal. Based on median lethal times (LT50), animals receiving 14 days prior exposure to 1.5 and 15 micrograms Ag/l were three to four times more resistant to silver than were previously unexposed organisms. The metal-induced resistance was not a sustained response. After organisms that had been acclimated to 15 micrograms/l had been transferred to clean water for two weeks, LT50 values determined with these animals were statistically indistinguishable from those calculated with non-acclimated control fish. With respect to nickel, a 32-day continuous-flow test was performed with the fathead minnow. Nickel was administered in duplicate at six exposure concentrations ranging from 0.038 to 0.733 mg/l in medium-hard water (100 mg CaCO3/l).

  19. Development and validation of a biotic ligand model for predicting chronic toxicity of lead to Ceriodaphnia dubia.

    PubMed

    Nys, Charlotte; Janssen, Colin R; Mager, Edward M; Esbaugh, Andrew J; Brix, Kevin V; Grosell, Martin; Stubblefield, William A; Holtze, Keith; De Schamphelaere, Karel A C

    2014-02-01

    While it is increasingly being recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the development of chronic BLMs has been less advanced for lead than for other metals. The authors investigated the univariate effects of Ca and pH on the chronic reproductive toxicity of Pb to Ceriodaphnia dubia at 4 levels. Calcium influenced chronic Pb toxicity to C. dubia only to a relatively small extent, whereas a high pH (8.2) provided strong protection against Pb toxicity (compared with lower pH levels). Based on this data set, a chronic Pb BLM for C. dubia was developed. The effect of pH was modeled as a single biotic ligand site competition by H(+) with a log stability constant for binding of H(+) to the biotic ligand (K(HBL)) of 7.6, while no other competitive constants were needed. The developed BLM was shown, in an independent validation with 3 other data sets, to be capable of predicting chronic Pb toxicity to different clones of C. dubia by an error of less than a factor of 2 in most synthetic and natural waters considered. The results add to the growing evidence that BLM-based risk assessment or water-quality criteria for Pb are likely to be more appropriate relative to hardness-based assessments or criteria.

  20. Transcriptomic studies on liver toxicity of acetaminophen.

    PubMed

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  1. Sauna as a valuable clinical tool for cardiovascular, autoimmune, toxicant- induced and other chronic health problems.

    PubMed

    Crinnion, Walter J

    2011-09-01

    Sauna therapy has been used for hundreds of years in the Scandinavian region as a standard health activity. Studies document the effectiveness of sauna therapy for persons with hypertension, congestive heart failure, and for post-myocardial infarction care. Some individuals with chronic obstructive pulmonary disease (COPD), chronic fatigue, chronic pain, or addictions also find benefit. Existing evidence supports the use of saunas as a component of depuration (purification or cleansing) protocols for environmentally-induced illness. While far-infrared saunas have been used in many cardiovascular studies, all studies applying sauna for depuration have utilized saunas with radiant heating units. Overall, regular sauna therapy (either radiant heat or far-infrared units) appears to be safe and offers multiple health benefits to regular users. One potential area of concern is sauna use in early pregnancy because of evidence suggesting that hyperthermia might be teratogenic.

  2. 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.

  3. 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.

  4. Short-term methods for estimating the chronic toxicity of effluents and receiving water to freshwater organisms. Third edition

    SciTech Connect

    Lewis, P.A.; Klemm, D.J.; Lazorchak, J.M.; Norberg-King, T.J.; Peltier, W.H.

    1994-07-01

    This manual describes four short-term (four- to seven-day) methods for estimating the chronic toxicity of effluents and receiving waters to three freshwater species: The fathead minnow, Pimephales promelas, a daphnid, Ceriodaphnia dubia, and a green alga, Selenastrum capricornutum. The methods include single and multiple concentration static renewal and non-renewal toxicity tests for effluents and receiving waters. Also included are guidelines on laboratory safety, quality assurance, facilities, equipment and supplies; dilution water; effluent and receiving water sample collection, preservation, shipping, and holding; test conditions; toxicity test data analysis; report preparation; and organism culturing, holding, and handling.

  5. Influence of salinity and organic carbon on the chronic toxicity of silver to mysids (Americamysis bahia) and silversides (Menidia beryllina).

    PubMed

    Ward, Timothy J; Boeri, Robert L; Hogstrand, Christer; Kramer, James R; Lussier, Suzanne M; Stubblefield, William A; Wyskiel, Derek C; Gorsuch, Joseph W

    2006-07-01

    Tests were conducted with mysids (Americamysis bahia) and silversides (Menidia beryllina) to evaluate the influence of salinity and organic carbon on the chronic toxicity of silver. During 7- and 28-d tests conducted at 10, 20, and 30% per hundred salinity, higher concentrations of dissolved silver generally were required to cause a chronic effect as the salinity of the seawater was increased. The 28-d mysid and silverside 20%-effective concentration values (expressed as dissolved silver) ranged from 3.9 to 60 and from 38 to 170 microg/L, respectively, over the salinity range. This pattern was not observed when the same test results were evaluated against the concentrations of free ionic silver (measured directly during toxicity tests), as predicted by the free-ion activity model. Increasing the concentration of dissolved organic carbon from 1 mg/L to the apparent maximum achievable concentration of 6 mg/L in seawater caused a slight decrease in chronic toxicity to silversides but had no effect on the chronic toxicity to mysids. The possible additive toxicity of silver in both food and water also was investigated. Even at the maximum achievable foodborne concentration, the chronic toxicity of silver added to the water was not affected when silver was also added to the food, based on the most sensitive endpoint (growth). However, although fecundity was unaffected at all five tested concentrations during the test with silver in water only, it was significantly reduced at the two highest waterborne silver concentrations (12 and 24 microg/L) during the test with silver dosed into food and water.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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

  15. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    PubMed

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs.

  16. Identification of compounds in heavy fuel oil that are chronically toxic to rainbow trout embryos by effects-driven chemical fractionation.

    PubMed

    Adams, Julie; Bornstein, Jason M; Munno, Keenan; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V

    2014-04-01

    The present study isolated and identified compounds in heavy fuel oil 7102 (HFO 7102) that are bioavailable and chronically toxic to rainbow trout embryos (Oncorhynchus mykiss). An effects-driven chemical fractionation combined the chemical separation of oil with toxicity testing and chemical analyses of each fraction to identify the major classes of compounds associated with embryo toxicity. Toxicity was assessed with 2 exposure methods, a high-energy chemical dispersion of oil in water, which included oil droplets in test solutions, and water accommodated fractions which were produced by oiled gravel desorption columns, and which did not contain visible oil droplets. Fractions of HFO with high concentrations of naphthalenes, alkanes, asphaltenes, and resins were nontoxic to embryos over the range of concentrations tested. In contrast, fractions enriched with 3- to 4-ringed alkyl polycyclic aromatic hydrocarbons (PAHs) were embryotoxic, consistent with published studies of crude oils and individual alkyl PAHs. The rank order of fraction toxicity did not vary between the exposure methods and was consistent with their PAH content; fractions with higher-molecular weight alkyl PAHs were the most toxic. Exposure of juvenile trout to most fractions of HFO induced higher activities of cytochrome P450 enzymes, with a rank order of potency that varied with exposure method and differed somewhat from that of embryotoxicity. Induction reflected the bioavailability of PAHs but did not accurately predict embryotoxicity.

  17. Evaluation of the developmental and reproductive toxicity of methoxychlor using an anuran (Xenopus tropicalis) chronic exposure model.

    PubMed

    Fort, Douglas J; Thomas, John H; Rogers, Robert L; Noll, Andra; Spaulding, Clinton D; Guiney, Patrick D; Weeks, John A

    2004-10-01

    The chronic toxicity of methoxychlor to the South African clawed frog, Xenopus (Silurana) tropicalis, was evaluated using a life cycle approach. The chronic exposure period ranged from mid-cell blastula stage [NF (Nieuwkoop and Faber, 1994) stage 8] to 90 days of exposure, during which time the organisms generally completed metamorphosis and emerged as juvenile frogs. Methoxychlor concentrations ranged from 1 to 100 micrograms/l. Methoxychlor concentrations >10 micrograms/l caused delayed development. Organisms exposed to 10 micrograms/l methoxychlor for 30 days showed enlarged thyroid glands with follicular hyperplasia. No increase in mortality or external malformation was observed at any of the test concentrations during early embryo-larval development (NF stage 8 to NF stage 46; ca. 2 days exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted after 90 days of exposure, however. Skewing of the sex ratio toward the female gender decreased ovary weight and number of oocytes, and increased oocyte immaturity and necrosis were noted at methoxychlor concentrations of 100 micrograms/l. Reductions in testis weight and sperm cell count were also detected at 100 micrograms/l methoxychlor. Results from these studies suggested that methoxychlor was capable of altering the rate of larval development, but did not adversely affect early embryo-larval development (2 days of exposure) as manifested in external malformations. Internal malformations, increases in the ratio of phenotypic females, were induced by chronic methoxychlor exposure. In addition, reproductive endpoints, most notably in the female specimens, were adversely affected by methoxychlor exposure. These studies add to the standardization and validation of a useful amphibian test methods capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.

  18. 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

  19. 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

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

    PubMed

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

    2013-01-01

    Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat. PMID:24146512

  1. Transcending chronic liver disease: a qualitative study.

    PubMed

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  2. 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.

  3. 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

  4. 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

  5. Chronic arsenic toxicity from drinking tubewell water in rural West Bengal.

    PubMed

    Guha Mazumder, D N; Chakraborty, A K; Ghose, A; Gupta, J D; Chakraborty, D P; Dey, S B; Chattopadhyay, N

    1988-01-01

    Hepatic damage caused by chronic exposure to arsenic has been frequently described. Here we report on 13 patients from West Bengal, India, who consumed large amounts of arsenic in drinking water. An epidemiological investigation of the study area showed evidence of chronic arsenical dermatosis and hepatomegaly in 62 (92.5%) of 67 members of families who drank contaminated water (arsenic level, 0.2-2 mg/l). In contrast, only six (6.25%) of 96 persons from the same area who drank safe water (arsenic level, <0.05 mg/l) had non-specific hepatomegaly, while none had skin lesions. Hepatomegaly occurred in all the 13 patients who were studied in detail, although five had splenomegaly. Biopsy of samples of liver from these patients revealed various degrees of fibrosis and expansion of the portal zone that resembled non-cirrhotic portal fibrosis (NCPF).

  6. 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.

  7. Chronic pain in Australia: a prevalence study.

    PubMed

    Blyth, F M; March, L M; Brnabic, A J; Jorm, L R; Williamson, M; Cousins, M J

    2001-01-01

    This study reports chronic pain prevalence in a randomly selected sample of the adult Australian population. Data were collected by Computer-Assisted Telephone Interview (CATI) using randomly generated telephone numbers and a two-stage stratified sample design. Chronic pain was defined as pain experienced every day for three months in the six months prior to interview. There were 17,543 completed interviews (response rate=70.8%). Chronic pain was reported by 17.1% of males and 20.0% of females. For males, prevalence peaked at 27.0% in the 65--69 year age group and for females, prevalence peaked at 31.0% in the oldest age group (80--84 years). Having chronic pain was significantly associated with older age, female gender, lower levels of completed education, and not having private health insurance; it was also strongly associated with receiving a disability benefit (adjusted OR=3.89, P<0.001) or unemployment benefit (adjusted OR=1.99, P<0.001); being unemployed for health reasons (adjusted OR=6.41, P<0.001); having poor self-rated health (adjusted OR=7.24, P<0.001); and high levels of psychological distress (adjusted OR=3.16, P<0.001). Eleven per cent of males and 13.5% of females in the survey reported some degree of interference with daily activities caused by their pain. Prevalence of interference was highest in the 55--59 year age group in both males (17.2%) and females (19.7%). Younger respondents with chronic pain were proportionately most likely to report interference due to pain, affecting 84.3% of females and 75.9% of males aged 20--24 years with chronic pain. Within the subgroup of respondents reporting chronic pain, the presence of interference with daily activities caused by pain was significantly associated with younger age; female gender; and not having private health insurance. There were strong associations between having interfering chronic pain and receiving disability benefits (adjusted OR=3.31, P<0.001) or being unemployed due to health reasons

  8. Short-term methods for estimating the chronic toxicity of effluents and receiving waters to freshwater organisms. Second edition

    SciTech Connect

    Weber, C.I.; Peltier, W.H.; Norberg-King, T.J.; Horning, W.B.; Kessler, F.A.

    1989-03-01

    This manual describes short-term (four- to seven-day) methods for estimating the chronic toxicity of effluents and receiving waters to the fathead minnow (Pimephales promelas), a cladoceran (Ceriodaphnia dubia), and a green alga (Selenastrum capricornutum). Also included are guidelines on laboratory safety, quality assurance, facilities and equipment, dilution water, effluent sampling and holding, data analysis, report preparation, and organism culturing and handling. Examples of the statistical analysis of test data are included with the methods. Supplementary information on statistical techniques for test design and analysis of toxicity test data is provided in the Appendices.

  9. 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).

  10. 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).

  11. 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.

  12. Drinking water toxicity study of the environmental contaminant--Bromate.

    PubMed

    Dongmei, Liu; Zhiwei, Wang; Qi, Zhu; Fuyi, Cui; Yujuan, Shan; Xiaodong, Liu

    2015-12-01

    Bromate is a byproduct of water disinfection that is produced when waters contain bromide treated with ozone. To investigate the level of the toxicity of bromate and find the most sensitive indicators in a short time, a series of toxicological assessments were conducted including the acute toxicity, cumulative toxicity, genetic toxicity and subacute toxicity of bromate (using Potassium Bromate to represent bromate). The LD50 of orally administered Potassium Bromate was 215 mg/kg in Wistar rats and 464 mg/kg in ICR mice. The cumulative toxicity of Potassium Bromate was not obvious. The Ames test, mouse bone marrow cell micronucleus test and mouse sperm abnormality test did not indicate mutagenicity. The results of the subacute study did not exhibit significant differences in most of the parameters, except the white blood cell count, which was significantly decreased in male rats. In addition, Potassium Bromate influenced the albumin, creatinine, total cholesterol, triglycerides and glucose levels in male rats to various extents. A thorough analysis of the above tests clearly demonstrates that bromate has toxicity, not obvious cumulative toxicity and the white blood cell count can be used as an indicator to reflect the toxicity of bromate and investigate bromate's toxic mechanism.

  13. 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

  14. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    PubMed Central

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity. PMID:24386634

  15. Chronic toxicity of zinc-spiked sediments; Evaluation of the acid volatile sulfide (AVS) model using Chironomus tentans

    SciTech Connect

    Sibley, P.K.; Ankley, G.T.; Cotter, A.M.; Leonard, E.N.

    1995-12-31

    Most research supporting AVS as a normalization phase for predicting the bioavailability of cationic metals from sediments is based on short-term laboratory exposures. Evidence supporting the theory with respect to chronic exposures is lacking. The purpose of this study, therefore, was to investigate whether the AVS model could predict toxicity to Chironomus tentans in a life cycle exposure to zinc-spiked sediments. Clean sediment was spiked with Zn to obtain nominal treatments ranging from {minus}2.35 to 58.5 {micro}g/g dw with respect to the molar difference between simultaneously extracted metal and AVS. The test was initiated with newly hatched larvae and carried through one complete generation (56 d) during which survival, growth, emergence, and reproduction were monitored. When SEM-AVS was < 0, the concentration of Zn in the pore water was low and no adverse effects were observed for any of the endpoints. Conversely, when SEM-AVS exceeded 0, a dose-dependent increase in the relative concentration of pore water Zn was observed. However, the absolute concentration of pore water Zn at each treatment declined with time, corresponding to an increase in AVS and to loss of Zn due to diffusion into the overlying water (renewed twice daily). Only when SEM-AVS exceeded approximately 6.5 were significant reductions in survival, growth, emergence, and reproductive output observed. In general, the chemical and biological data of this study agree with observations made in short-term exposures and thus support the use of AVS as a normalization phase for predicting the potential for toxicity in metal-contaminated sediments.

  16. Chronic toxicity and hazard assessment of an inorganic mixture simulating irrigation drainwater to razorback sucker and bonytail

    USGS Publications Warehouse

    Hamilton, Steven J.; Buhl, Kevin J.; Bullard, Fern A.; Little, Edward E.

    2000-01-01

    We conducted two 90 day chronic toxicity studies with two endangered fish, razorback sucker and bonytail. Swim-up larvae were exposed in a reconstituted water simulating the middle Green River. The toxicant mixture simulated the environmental ratio and concentrations of inorganics reported in a Department of the Interior study for the mouth of Ashley Creek on the Green River, and was composed of nine elements. The mixture was tested at 1X, 2X, 4X, 8X, and 16X where X was the measured environmental concentration (2 μg/L arsenic, 630 μg/L boron, 10 μg/L copper, 5 μg/L molybdenum, 51 μg/L selenate, 8 μg/L selenite, 33 μg/L uranium, 2 μg/L vanadium, and 20 μg/L zinc). Razorback sucker had reduced survival after 60 days exposure to the inorganic mixture at 8X, whereas growth was reduced after 30 and 60 days at 2X and after 90 days at 4X. Bonytail had reduced survival after 30 days exposure at 16X, whereas growth was reduced after 30, 60, and 90 days at 8X. Swimming performance of razorback sucker and bonytail were reduced after 60 and 90 days of exposure at 8X. Whole-body residues of copper, selenium, and zinc increased in a concentration-response manner and seemed to be regulated at 90 days of exposure at 4X and lower treatments for razorback sucker, and at 8X and lower for bonytail. Adverse effects occurred in fish with whole-body residues of copper, selenium, and zinc similar to those causing similar effects in other fish species. Comparison of adverse effect concentrations with measured environmental concentrations showed a high hazard to the two endangered fish. Irrigation activities may be a contributing factor to the decline of these endangered fishes in the middle Green River. 

  17. The role of metabolic biomarkers in drug toxicity studies.

    PubMed

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  18. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.; Taylor, Larry

    2008-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be

  19. Chronic toxicity evaluation of the flame retardant tris (2-butoxyethyl) phosphate (TBOEP) using Daphnia magna transcriptomic response.

    PubMed

    Giraudo, Maeva; Douville, Mélanie; Houde, Magali

    2015-08-01

    Tris (2-butoxyethyl) phosphate (TBOEP) is an organophosphorous-containing flame retardant (OPFR) of high production volume used in a broad range of applications. The use of TBOEP containing products has resulted in its release and ubiquitous occurrence in the aquatic environment. In this study, Daphnia magna transcriptomic response was measured by microarray to evaluate sublethal effects of TBOEP as part of a multi-level biological approach including specific gene transcription measured by qRT-PCR, enzyme activity, and life-history endpoints (i.e., survival, growth and reproduction). Chronic exposure (21 d) to a range of sublethal concentrations of TBOEP (14.7-1470μgL(-1)) did not impact growth, survival or reproduction, although the number of offspring decreased between the lowest and the highest dose. Gene transcription profiling by microarray analysis revealed that 101 genes were differentially transcribed in response to TBOEP (fold change treated/control ±1, p<0.05). Most of the responding genes were involved in protein metabolism (9), biosynthesis (4) and energy metabolism (6) indicating that TBOEP could have chronic toxic effects on aquatic organisms at sublethal doses by disrupting essential biological pathways. Nine genes were found to be commonly affected by more than one dose, including a gene coding for cathepsin D and multiple isoforms of genes coding for hemoglobin, suggesting potential biomarkers of interest. Microarray results were confirmed by qRT-PCR and measurements at the protein level as cathepsin D enzymatic activity increased significantly in the highest dose treatment. Results highlight the relevance of using the transcriptomic response of D. magna as a first line of evidence to unravel the mode of action of chemicals.

  20. Chronic toxicity evaluation of the flame retardant tris (2-butoxyethyl) phosphate (TBOEP) using Daphnia magna transcriptomic response.

    PubMed

    Giraudo, Maeva; Douville, Mélanie; Houde, Magali

    2015-08-01

    Tris (2-butoxyethyl) phosphate (TBOEP) is an organophosphorous-containing flame retardant (OPFR) of high production volume used in a broad range of applications. The use of TBOEP containing products has resulted in its release and ubiquitous occurrence in the aquatic environment. In this study, Daphnia magna transcriptomic response was measured by microarray to evaluate sublethal effects of TBOEP as part of a multi-level biological approach including specific gene transcription measured by qRT-PCR, enzyme activity, and life-history endpoints (i.e., survival, growth and reproduction). Chronic exposure (21 d) to a range of sublethal concentrations of TBOEP (14.7-1470μgL(-1)) did not impact growth, survival or reproduction, although the number of offspring decreased between the lowest and the highest dose. Gene transcription profiling by microarray analysis revealed that 101 genes were differentially transcribed in response to TBOEP (fold change treated/control ±1, p<0.05). Most of the responding genes were involved in protein metabolism (9), biosynthesis (4) and energy metabolism (6) indicating that TBOEP could have chronic toxic effects on aquatic organisms at sublethal doses by disrupting essential biological pathways. Nine genes were found to be commonly affected by more than one dose, including a gene coding for cathepsin D and multiple isoforms of genes coding for hemoglobin, suggesting potential biomarkers of interest. Microarray results were confirmed by qRT-PCR and measurements at the protein level as cathepsin D enzymatic activity increased significantly in the highest dose treatment. Results highlight the relevance of using the transcriptomic response of D. magna as a first line of evidence to unravel the mode of action of chemicals. PMID:25855008

  1. Acute and chronic toxicity testing of bisphenol A with aquatic invertebrates and plants.

    PubMed

    Mihaich, Ellen M; Friederich, Urs; Caspers, Norbert; Hall, A Tilghman; Klecka, Gary M; Dimond, Stephen S; Staples, Charles A; Ortego, Lisa S; Hentges, Steven G

    2009-07-01

    Bisphenol A (BPA, 4,4'-isopropylidine diphenol) is a commercially important chemical used primarily as an intermediate in the production of polycarbonate plastic and epoxy resins. Extensive effect data are currently available, including long-term studies with BPA on fish, amphibians, crustaceans, and mollusks. The aim of this study was to perform additional tests with a number of aquatic invertebrates and an aquatic plant. These studies include acute tests with the midge (Chironomus tentans) and the snail (Marisa cornuarietis), and chronic studies with rotifers (Brachionus calyciflorus), amphipods (Hyalella azteca), and plants (Lemna gibba). The effect data on different aquatic invertebrate and plant species presented in this paper correspond well with the effect and no-effect concentrations (NOECs) available from invertebrate studies in the published literature and are within the range found for other aquatic species tested with BPA. PMID:19327838

  2. Comparison of four chronic sediment toxicity tests using selected marine/estuarine tests species

    SciTech Connect

    Sims, I.; Fleming, R.

    1995-12-31

    Several draft standard guidelines exist for acute marine/estuarine sediment bioassays which measure lethality over a 4 to 14 day exposure period. Although these are very useful tools for certain applications, such tests may not be useful for discriminating between sediments with the low levels of contaminants most likely to be found in UK estuaries. For this application, chronic sediment bioassays are required which allow the measurement of both lethal and sublethal effects (growth, development and reproduction). Some chronic bioassays are currently being developed for estuarine sediments by workers in Europe, America and Canada. The objectives of the study presented here were to compare four bioassays, currently in development, in terms of their sensitivity to sediment-bound lindane and to differences in particle size. The test species selected for the study were Corophium volutator, Arenicola marina, Macoma Balthica and Neanthes arenaceodentata. Three sediment types were used: high, medium and low percentage of fine material, These were achieved using mixtures of silica sand and a fine, natural, estuarine sediment, and spiked with lindane using a spiking protocol developed at WRc. The results of the study will be presented.

  3. Is Combination Therapy for Chronic Hepatitis C Toxic for Cardiac Function?

    PubMed Central

    Almawardy, Ramzy; Elhammady, Walid; Mousa, Nasser; Abotaleb, Sherif

    2012-01-01

    Background Many types of cardiovascular complications such as; cardiac arrhythmias, impaired cardiac function, myocardial ischemia and decreased left ventricular function, have been attributed to interferon therapy. Objectives The aim of this study was to evaluate the effects of combination therapy pegylated interferon and ribavirin on left ventricular systolic and diastolic functions in patients with a chronic hepatitis C infection. Patients and Methods A total of 120 patients, eligible for hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin, were included in this study. All patients underwent a full cardiovascular baseline examination including; detailed medical history, thorough clinical examination, 12 lead electrocardiogram (ECG), and echocardiography. A cardiac evaluation was performed at the beginning and six months after starting combination therapy. Results No significant changes regarding cardiac symptoms including; shortness of breath, cough, palpitations, chest pain and hypertension, were found during or six months after starting the combined therapy. ECG findings showed statistically non-significant decreases in the QT interval, while corrected QT showed statistically non-significant increases six months after beginning combined therapy, when compared to their values before treatment. Also with regard to the echocardiography findings, there was no statistically significant difference found between any of the echocardiography parameters six months after starting combined therapy compared to their values before treatment. Conclusions The results of our study suggest that, combination therapy does not cause a significant deterioration in cardiac function in patients with a chronic hepatitis C infection, and it may be used safely in patients without cardiac disease. PMID:23105944

  4. Toxicity study of oxfendazole in pregnant sows.

    PubMed

    Morgan, D W

    1982-08-21

    The safety of oxfendazole when administered to pregnant sows was assessed. Thirty-six pregnant sows were dosed orally on repeated occasions at dose rates of 4.5 mg/kg bodyweight and 13.5 mg/kg during the critical period of embryo organogenesis and implantation. Twelve sows were observed as untreated controls. Oxfendazole was administered as 6.48 per cent medicated pellets. Records were kept of the reproductive performance of all 48 sows. There were no obviously drug-related clinical signs of toxicity in the sows after treatment with oxfendazole, neither were drug-related anatomical or behavioural abnormalities detected in the newborn pigs.

  5. Studies on the mechanism of benzene toxicity.

    PubMed Central

    Snyder, R; Dimitriadis, E; Guy, R; Hu, P; Cooper, K; Bauer, H; Witz, G; Goldstein, B D

    1989-01-01

    Using the 59Fe uptake method of Lee et al. it was shown that erythropoiesis in female mice was inhibited following IP administration of benzene, hydroquinone, p-benzoquinone, and muconaldehyde. Toluene protected against the effects of benzene. Coadministration of phenol plus either hydroquinone or catechol resulted in greatly increased toxicity. The combination of metabolites most effective in reducing iron uptake was hydroquinone plus muconaldehyde. We have also shown that treating animals with benzene leads to the formation of adducts of bone marrow DNA as measured by the 32P-postlabeling technique. PMID:2792049

  6. The chronic toxicity of ZnO nanoparticles and ZnCl2 to Daphnia magna and the use of different methods to assess nanoparticle aggregation and dissolution.

    PubMed

    Adam, Nathalie; Schmitt, Claudia; Galceran, Josep; Companys, Encarna; Vakurov, Alexander; Wallace, Rachel; Knapen, Dries; Blust, Ronny

    2014-11-01

    In this study, the effect of ZnO nanoparticles and ZnCl2 on growth, reproduction and accumulation of zinc in Daphnia magna was determined in a 21-day chronic toxicity test. A variety of techniques were used to distinguish the free zinc ion, dissolved, nanoparticle and aggregated zinc fraction in the Daphnia test medium. The results showed similar chronic effects on growth, reproduction and accumulation for the ZnO nanoparticles (EC10, 20, 50 reproduction: 0.030, 0.049, 0.112 mg Zn/l) and the ZnCl2 (EC10, 20, 50 reproduction: 0.014, 0.027, 0.082 mg Zn/l). A large fraction of the nanoparticles rapidly dissolved after introduction in the exposure medium. Aggregation of nanoparticles was also observed but within 48 h of exposure most of these ZnO aggregates were dissolved. Based on the combined dissolution kinetics and toxicity results, it can be concluded that the toxicological effects of ZnO nanoparticles at the chronic level can be largely attributed to the dissolved fraction rather than the nanoparticles or initially formed aggregates.

  7. A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

    PubMed

    Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

    2016-07-01

    Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (<0.45-μm filtered fraction) at 28 °C were 115 μg/L and 185 μg/L, respectively. The toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC. PMID:26643415

  8. A chronic toxicity test for the tropical marine snail Nassarius dorsatus to assess the toxicity of copper, aluminium, gallium, and molybdenum.

    PubMed

    Trenfield, Melanie A; van Dam, Joost W; Harford, Andrew J; Parry, David; Streten, Claire; Gibb, Karen; van Dam, Rick A

    2016-07-01

    Chronic toxicity test methods for assessing the toxicity of contaminants to tropical marine organisms are generally lacking. A 96-h chronic growth rate toxicity test was developed for the larval stage of the tropical dogwhelk, Nassarius dorsatus. Growth rates of N. dorsatus larvae were assessed following exposures to copper (Cu), aluminium (Al), gallium (Ga), and molybdenum (Mo). Exposure to Cu at 28 °C validated the sensitivity of the test method, with 10% (EC10) and 50% (EC50) effect concentrations of 4.2 μg/L and 7.3 μg/L Cu, respectively. The EC10 and EC50 values for Al (<0.45-μm filtered fraction) at 28 °C were 115 μg/L and 185 μg/L, respectively. The toxicity of Cu and Al was also assessed at 24 °C and 31 °C, representing average year-round water temperatures for subtropical and tropical Australian coastal environments. At 24 °C, the growth rate of control larvae was reduced by 52% compared with the growth rate at 28 °C and there was an increase in sensitivity to Cu (EC50 = 4.7 μg/L) but a similar sensitivity to Al (EC50 = 180 μg/L). At 31 °C the control growth rate increased by 35% from that measured at 28 °C and there was reduced sensitivity to both Cu and Al (EC50s = 8.5 μg/L and 642 μg/L, respectively). There was minimal toxicity resulting from Ga (EC50 = 4560 μg/L) and Mo (no effect at ≤7000 μg/L Mo). Environ Toxicol Chem 2016;35:1788-1795. © 2015 SETAC.

  9. Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats

    PubMed Central

    Razmaraii, Nasser; Babaei, Hossein; Mohajjel Nayebi, Alireza; Assadnassab, Gholamreza; Ashrafi Helan, Javad; Azarmi, Yadollah

    2016-01-01

    Purpose: The aim of the present study was to determine the ability of grape seed extract (GSE) as a powerful antioxidant in preventing adverse effect of doxorubicin (DOX) on heart function. Methods: Male rats were divided into three groups: control, DOX (2 mg/kg/48h, for 12 days) and GSE (100 mg/kg/24h, for 16 days) plus DOX. Left ventricular (LV) function and hemodynamic parameters were assessed using echocardiography, electrocardiography and a Millar pressure catheter. Histopathological analysis and in vitro antitumor activity were also evaluated. Results: DOX induced heart damage in rats through decreasing the left ventricular systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening and contractility index as demonstrated by echocardiography, electrocardiography and hemodynamic parameters relative to control group. Our data demonstrated that GSE treatment markedly attenuated DOX-induced toxicity, structural changes in myocardium and improved ventricular function. Additionally, GSE did not intervene with the antitumor effect of DOX. Conclusion: Collectively, the results suggest that GSE is potentially protective against DOX-induced toxicity in rat heart and maybe increase therapeutic index of DOX in human cancer treatment. PMID:27766227

  10. Study on wastewater toxicity using ToxTrak™ method.

    PubMed

    Liwarska-Bizukojc, Ewa; Ślęzak, Radoslaw; Klink, Małgorzata

    2016-05-01

    ToxTrak™ method is an analytical tool for the measurement of toxicity of drinking water, wastewater and natural water. It is based upon the estimation of the inhibitive effect on bacterial respiration processes. The main aim of this work was to test the applicability of ToxTrak™ method in the assessment of wastewater toxicity in a full-scale WWTP in Poland. In order to achieve it, the study was divided into two parts. First, the validation of ToxTrak™ method was performed. Second, wastewater toxicity was monitored in the long- and short-term campaigns. Validation of ToxTrak™ method revealed that the indigenous biomass (mixed cultures of activated sludge microorganisms) was more sensitive than Escherichia coli for both materials (wastewater and phenol) tested. The values of degree of inhibition determined for phenol towards indigenous biomass and E. coli were close to each other, and no statistically significant difference between them was found. It confirmed the reliability of the results obtained with the help of ToxTrak™ test. The toxicity of the effluent was always lower than that of the influent and the linear correlation between them was found. Despite, the decrease of wastewater toxicity in the WWTP, the effluents were ranked as toxic or highly toxic according to the classification of wastewater based upon the acute toxicity. PMID:26832868

  11. Proper interpretation of chronic toxicity studies and their statistics: A critique of "Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example".

    PubMed

    Kissling, Grace E; Haseman, Joseph K; Zeiger, Errol

    2015-09-01

    A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP's statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP, 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800×0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP's decision making process, overstates the number of statistical comparisons made, and ignores the fact that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus' conclusion that such obvious responses merely "generate a hypothesis" rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors.

  12. Proper interpretation of chronic toxicity studies and their statistics: A critique of "Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example".

    PubMed

    Kissling, Grace E; Haseman, Joseph K; Zeiger, Errol

    2015-09-01

    A recent article by Gaus (2014) demonstrates a serious misunderstanding of the NTP's statistical analysis and interpretation of rodent carcinogenicity data as reported in Technical Report 578 (Ginkgo biloba) (NTP, 2013), as well as a failure to acknowledge the abundant literature on false positive rates in rodent carcinogenicity studies. The NTP reported Ginkgo biloba extract to be carcinogenic in mice and rats. Gaus claims that, in this study, 4800 statistical comparisons were possible, and that 209 of them were statistically significant (p<0.05) compared with 240 (4800×0.05) expected by chance alone; thus, the carcinogenicity of Ginkgo biloba extract cannot be definitively established. However, his assumptions and calculations are flawed since he incorrectly assumes that the NTP uses no correction for multiple comparisons, and that significance tests for discrete data operate at exactly the nominal level. He also misrepresents the NTP's decision making process, overstates the number of statistical comparisons made, and ignores the fact that the mouse liver tumor effects were so striking (e.g., p<0.0000000000001) that it is virtually impossible that they could be false positive outcomes. Gaus' conclusion that such obvious responses merely "generate a hypothesis" rather than demonstrate a real carcinogenic effect has no scientific credibility. Moreover, his claims regarding the high frequency of false positive outcomes in carcinogenicity studies are misleading because of his methodological misconceptions and errors. PMID:25261588

  13. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.

    2009-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

  14. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  15. Category III chronic prostatitis/chronic pelvic pain syndrome: insights from the National Institutes of Health Chronic Prostatitis Collaborative Research Network studies.

    PubMed

    Nickel, J Curtis; Alexander, Richard B; Anderson, Rodney; Berger, Richard; Comiter, Craig V; Datta, Nand S; Fowler, Jackson E; Krieger, John N; Landis, J Richard; Litwin, Mark S; McNaughton-Collins, Mary; O'Leary, Michael P; Pontari, Michel A; Schaeffer, Anthony J; Shoskes, Daniel A; White, Paige; Kusek, John; Nyberg, Leroy

    2008-07-01

    Chronic prostatitis/chronic pelvic pain syndrome remains an enigmatic medical condition. Creation of the National Institutes of Health-funded Chronic Prostatitis Collaborative Research Network (CPCRN) has stimulated a renewed interest in research on and clinical aspects of chronic prostatitis/chronic pelvic pain syndrome. Landmark publications of the CPCRN document a decade of progress. Insights from these CPCRN studies have improved our management of chronic prostatitis/chronic pelvic pain syndrome and offer hope for continued progress. PMID:18765132

  16. Development of biotic ligand models for chronic manganese toxicity to fish, invertebrates, and algae.

    PubMed

    Peters, Adam; Lofts, Stephen; Merrington, Graham; Brown, Bruce; Stubblefield, William; Harlow, Keven

    2011-11-01

    Ecotoxicity tests were performed with fish, invertebrates, and algae to investigate the effect of water quality parameters on Mn toxicity. Models were developed to describe the effects of Mn as a function of water quality. Calcium (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and magnesium (Mg) also provides a protective effect for invertebrates. Protons have a protective effect on Mn toxicity to algae. The models derived are consistent with models of the toxicity of other metals to aquatic organisms in that divalent cations can act as competitors to Mn toxicity in fish and invertebrates, and protons act as competitors to Mn toxicity in algae. The selected models are able to predict Mn toxicity to the test organisms to within a factor of 2 in most cases. Under low-pH conditions invertebrates are the most sensitive taxa, and under high-pH conditions algae are most sensitive. The point at which algae become more sensitive than invertebrates depends on the Ca concentration and occurs at higher pH when Ca concentrations are low, because of the sensitivity of invertebrates under these conditions. Dissolved organic carbon concentrations have very little effect on the toxicity of Mn to aquatic organisms.

  17. Development of biotic ligand models for chronic manganese toxicity to fish, invertebrates, and algae.

    PubMed

    Peters, Adam; Lofts, Stephen; Merrington, Graham; Brown, Bruce; Stubblefield, William; Harlow, Keven

    2011-11-01

    Ecotoxicity tests were performed with fish, invertebrates, and algae to investigate the effect of water quality parameters on Mn toxicity. Models were developed to describe the effects of Mn as a function of water quality. Calcium (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and magnesium (Mg) also provides a protective effect for invertebrates. Protons have a protective effect on Mn toxicity to algae. The models derived are consistent with models of the toxicity of other metals to aquatic organisms in that divalent cations can act as competitors to Mn toxicity in fish and invertebrates, and protons act as competitors to Mn toxicity in algae. The selected models are able to predict Mn toxicity to the test organisms to within a factor of 2 in most cases. Under low-pH conditions invertebrates are the most sensitive taxa, and under high-pH conditions algae are most sensitive. The point at which algae become more sensitive than invertebrates depends on the Ca concentration and occurs at higher pH when Ca concentrations are low, because of the sensitivity of invertebrates under these conditions. Dissolved organic carbon concentrations have very little effect on the toxicity of Mn to aquatic organisms. PMID:21842490

  18. Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity

    PubMed Central

    Cortes, Jorge E.; Hochhaus, Andreas; Saglio, Giuseppe; le Coutre, Philipp; Porkka, Kimmo; Mustjoki, Satu; Mohamed, Hesham; Shah, Neil P.

    2016-01-01

    BACKGROUND The proliferation of clonal cytotoxic T‐cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib‐treated patients with newly diagnosed CML in chronic phase (CML‐CP), CML‐CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid‐blast phase were analyzed. RESULTS Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib‐treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML‐CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression‐free and overall survival rates were significantly longer in patients with CML‐CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS Overall, lymphocytosis occurred and persisted in many dasatinib‐treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398–1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. PMID:26998677

  19. Sensitivity of early life stages of freshwater mussels (Unionidae) to acute and chronic toxicity of lead, cadmium, and zinc in water

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Ivey, C.D.; Hardesty, D.K.; May, T.W.; Augspurger, T.; Roberts, A.D.; Van Genderen, E.; Barnhart, M.C.

    2010-01-01

    Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d exposures with two- or four-month-old mussels in reconstituted soft water. The 24-h median effect concentrations (EC50s) for fatmucket glochidia (>299??g Pb/L, >227??g Cd/L, 2,685??g Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426??g Pb/L, 199??g Cd/L, 1,700??g Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298??g Pb/L, 16??g Cd/L, 151 and 175??g Zn/L) and Neosho mucket (188??g Pb/L, 20??g Cd/L, 145??g Zn/L). Chronic values for fatmucket were 10??g Pb/L, 6.0??g Cd/L, and 63 and 68??g Zn/L. When mussel data from the present study and the literature were included in updated databases for deriving U.S. Environmental Protection Agency water quality criteria, mussel genus mean acute values were in the lower percentiles of the sensitivity distribution of all freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus mean chronic value was the lowest value ever reported for Pb (the 9th percentile) but was near the middle of the sensitivity distribution for Cd (the 61st percentile) or Zn (the 44th percentile). These results indicate that mussels were relatively sensitive to the acute toxicity of these three metals and to the chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of Cd or Zn compared to other freshwater species. ?? 2010 SETAC.

  20. Chronic toxicity of a homologous series of alcohol ethoxylate surfactants to Daphnia magna

    SciTech Connect

    Gillespie, W.B. Jr.; Rodgers, J.H. Jr.; Wong, D.C.L.; Dorn, P.B.

    1995-12-31

    The effects of three homologous nonionic surfactants were evaluated in a series of 21 d Daphnia magna flow-through laboratory experiments. No observed effects concentrations and effects concentrations for survival and reproduction were determined for three linear alcohol ethoxylate (LAE) surfactants with average carbon chain lengths of 10, 12.5, and 14.5 and average ethylene oxide units/mole of 6, 6.5, and 7, respectively. Mean measured concentrations of LAE in laboratory experiments ranged from 0.91 to 16.91 mg/L, 0.38 to 5.21 mg/L and 0.31 to 1.83 mg/L for C{sub 10}, C{sub 12.5}, and C{sub 14.5} LAEs, respectively. Daphnid survival NOECs were 2.8 mg/L (C{sub 10}), 1.8 mg/L (C{sub 12.5}), and 0.79 mg/L (C{sub 14.5}). Daphnid survival and reproduction were equally sensitive to the C{sub 10} and C{sub 14.5} surfactants, however, reproduction was more sensitive than survival for the C{sub 12.5} surfactant. Reproduction NOECs were 2.8, 0.77, and 0.79 mg/L for the C{sub 10}, C{sub 12.5}, and C{sub 14.5} LAEs, respectively. The 21 d chronic survival NOECs for daphnids were similar to NOECs for cladoceran densities obtained in outdoor stream mesocosm studies conducted at the University of Mississippi Field Station. These results indicate a relationship of approximately 1:1 between the chronic laboratory and field results.

  1. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management. PMID:26854702

  2. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management.

  3. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Cao, Xingyuan

    2015-09-01

    Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day. PMID:26397222

  4. Studies on toxicity of OTEC plant components on marine animals from the Gulf of Mexico. Final report, September 1, 1978-November 30, 1980

    SciTech Connect

    Venkataramiah, A.; Lakshmi, G.J.; Best, C.; Gunter, G.; Hartwig, E.; Wilde, P.

    1981-06-01

    Ammonia and chlorine were chosen for toxicity studies as they pose the greatest potential environmental threat. Acute and chronic bioassays determined the LT/sub 50/, LC/sub 50/ and the behavior of mullet (Mugil cephalus), sargassum shrimp (Latreutes focorum) and filefish (Monocanthus hispidus). The chronic bioassays were carried out mainly in sublethal concentrations of ammonia and chlorine. The findings indicate that high concentrations of ammonia and chlorine from the OTEC plants are toxic to marine animals. Also the level of toxicity is related to the species, their habitats and life stages.

  5. Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress.

    PubMed

    Marques-Aleixo, Inês; Santos-Alves, Estela; Mariani, Diogo; Rizo-Roca, David; Padrão, Ana I; Rocha-Rodrigues, Sílvia; Viscor, Ginés; Torrella, J Ramon; Ferreira, Rita; Oliveira, Paulo J; Magalhães, José; Ascensão, António

    2015-01-01

    Doxorubicin (DOX) is an anti-cancer agent whose clinical usage results in a cumulative and dose-dependent cardiotoxicity. We have previously shown that exercise performed prior to DOX treatment reduces the resulting cardiac(mito) toxicity. We sought to determine the effects on cardiac mitochondrial toxicity of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free-wheel activity-FW) when used prior and during DOX treatment. Male-young Sprague-Dawley rats were divided into six groups (n=6 per group): SAL+SED (saline sedentary), SAL+TM (12-weeks TM), SAL+FW (12-weeks FW), DOX+SED (7-weeks of chronic DOX treatment 2mg/kg per week), DOX+TM and DOX+FW. DOX administration started 5weeks after the beginning of the exercise protocol. Heart mitochondrial ultrastructural alterations, mitochondrial function (oxygen consumption and membrane potential), semi-quantification of oxidative phosphorylation (OXPHOS) proteins and their in-gel activity, as well as proteins involved in mitochondrial oxidative stress (SIRT3, p66shc and UCP2), biogenesis (PGC1α and TFAM), acetylation and markers for oxidative damage (carbonyl groups, MDA,SH, aconitase, Mn-SOD activity) were evaluated. DOX treatment resulted in ultrastructural and functional alterations and decreased OXPHOS. Moreover, DOX decreased complex I activity and content, mitochondrial biogenesis (TFAM), increased acetylation and oxidative stress. TM and FW prevented DOX-induced alteration in OXPHOS, the increase in oxidative stress, the decrease in complex V activity and in complex I activity and content. DOX-induced decreases in TFAM and SIRT3 content were prevented by TM only. Both chronic models of physical exercise performed before and during the course of sub-chronic DOX treatment translated into an improved mitochondrial bioenergetic fitness, which may result in part from the prevention of mitochondrial oxidative stress and damage. PMID:25446396

  6. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review

    PubMed Central

    Geamănu (Pancă), A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, CD; Voinea, LM

    2014-01-01

    Abstract Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects. PMID:25408748

  7. Subchronic (13-week) toxicity and prenatal developmental toxicity studies of dietary astaxanthin in rats.

    PubMed

    Vega, Katherine; Edwards, James; Beilstein, Paul

    2015-12-01

    Two studies examined the effects of dietary astaxanthin on Hanlbm Wistar (SPF) rats. Male and female rats receiving astaxanthin concentrations up to 1.52% of the feed for 13 weeks showed no evidence of toxicity; no effects were noted in the offspring of female rats exposed to astaxanthin at up to 1.39% of the feed during the period of organogenesis (GD 7-16). Discoloration of the feces and yellow pigmentation of adipose tissue was seen in the 13-week study, an intrinsic property of the substance, and not a sign of toxicity. Differences between the control and astaxanthin groups, some of which reached statistical significance, were generally sporadic (i.e., transient and/or not related to astaxanthin concentration) and not considered of biological or toxicological significance. Blood cholesterol levels, for example, were greater in animals receiving astaxanthin for 13 weeks, but remained within the normal range. The highest dietary concentration of astaxanthin in each of the studies is proposed as a no-observable-adverse-effect level (NOAEL). Specifically, 1.52% for the 13-week study, corresponding to a mean intake of 1033 mg/kg bw/day (range: 880-1240 mg/kg bw/day), and 1.39% for the developmental toxicity study, corresponding to a mean intake of approximately 830 mg/kg bw/day (range: 457-957 mg/kg bw/day).

  8. Short term chronic and acute toxicity screening of water and sediment using fathead minnows, daphnids, rotifers (Rotox[reg sign]) and light emitting bacteria (Microtox[reg sign]), Ambient Stream Monitoring, summers of 1990 and 1991

    SciTech Connect

    Moses, J.; Wade, D.C.

    1992-07-01

    Toxicological evaluation of water column and sediment samples from six locations in the Ambient Stream Monitoring fixed station network was initiated in 1986 using short-term chronic bioassay methods. Toxicological evaluation of six additional stations was initiated in 1990. Chronic studies were conducted at one of these new stations and acute screening methods were used at all twelve locations now included in the activity. This report provides results from studies conducted during the summers of 1990 and 1991. The 1990--91 studies evaluated toxicity of stream water and porewater extracted from sediments as test media, whereas previous studies evaluated water and sediment elutriate samples.

  9. Short term chronic and acute toxicity screening of water and sediment using fathead minnows, daphnids, rotifers (Rotox{reg_sign}) and light emitting bacteria (Microtox{reg_sign}), Ambient Stream Monitoring, summers of 1990 and 1991

    SciTech Connect

    Moses, J.; Wade, D.C.

    1992-07-01

    Toxicological evaluation of water column and sediment samples from six locations in the Ambient Stream Monitoring fixed station network was initiated in 1986 using short-term chronic bioassay methods. Toxicological evaluation of six additional stations was initiated in 1990. Chronic studies were conducted at one of these new stations and acute screening methods were used at all twelve locations now included in the activity. This report provides results from studies conducted during the summers of 1990 and 1991. The 1990--91 studies evaluated toxicity of stream water and porewater extracted from sediments as test media, whereas previous studies evaluated water and sediment elutriate samples.

  10. Studies on bioremediation of polycyclic aromatic hydrocarbon-contaminated sediments: bioavailability, biodegradability, and toxicity issues.

    PubMed

    Tabak, Henry H; Lazorchak, James M; Lei, Li; Khodadoust, Amid P; Antia, Jimmy E; Bagchi, Rajesh; Suidan, Makram T

    2003-03-01

    The widespread contamination by polycyclic aromatic hydrocarbons (PAHs) has created a need for cost-effective bioremediation processes. This research studied a chronically PAH-contaminated estuarine sediment from the East River (ER; NY, USA) characterized by high concentrations of PAHs (approximately 4-190 ppm), sulfide, and metals and a marine sediment from New York/ New Jersey Harbor (NY/NJH; USA) with only trace quantities of PAHs (0.1-0.6 ppm). The focus was to examine the relationship between bioavailability of PAHs and their biological removal in a slurry system. Freshwater and marine sediment toxicity tests were conducted to measure baseline toxicity of both sediments to amphipods, aquatic worms, fathead and sheepshead minnow larvae, and a vascular plant; to determine the cause of toxicity; and to evaluate the effectiveness of the biotreatment strategies in reducing toxicity. Results showed the ER sediment was acutely toxic to all freshwater and marine organisms tested and that the toxicity was mainly caused by sulfide, PAHs, and metals present in the sediment. In spite of the high toxicity, most of the PAH compounds showed significant degradation in the aerobic sediment/water slurry system if the initial high oxygen demand due to the high sulfide content of the sediment was overcome. The removal of PAHs by biodegradation was closely related to their desorbed amount in 90% isopropanol solution during 24 h of contact, while the desorption of model PAH compounds from freshly spiked NY/NJH sediment did not describe the bioavailability of PAHs in the East River sediment well. The research improves our understanding of bioavailability as a controlling factor in bioremediation of PAHs and the potential of aerobic biodegradation for PAH removal and ecotoxicity reduction. PMID:12627632

  11. Studies on bioremediation of polycyclic aromatic hydrocarbon-contaminated sediments: bioavailability, biodegradability, and toxicity issues.

    PubMed

    Tabak, Henry H; Lazorchak, James M; Lei, Li; Khodadoust, Amid P; Antia, Jimmy E; Bagchi, Rajesh; Suidan, Makram T

    2003-03-01

    The widespread contamination by polycyclic aromatic hydrocarbons (PAHs) has created a need for cost-effective bioremediation processes. This research studied a chronically PAH-contaminated estuarine sediment from the East River (ER; NY, USA) characterized by high concentrations of PAHs (approximately 4-190 ppm), sulfide, and metals and a marine sediment from New York/ New Jersey Harbor (NY/NJH; USA) with only trace quantities of PAHs (0.1-0.6 ppm). The focus was to examine the relationship between bioavailability of PAHs and their biological removal in a slurry system. Freshwater and marine sediment toxicity tests were conducted to measure baseline toxicity of both sediments to amphipods, aquatic worms, fathead and sheepshead minnow larvae, and a vascular plant; to determine the cause of toxicity; and to evaluate the effectiveness of the biotreatment strategies in reducing toxicity. Results showed the ER sediment was acutely toxic to all freshwater and marine organisms tested and that the toxicity was mainly caused by sulfide, PAHs, and metals present in the sediment. In spite of the high toxicity, most of the PAH compounds showed significant degradation in the aerobic sediment/water slurry system if the initial high oxygen demand due to the high sulfide content of the sediment was overcome. The removal of PAHs by biodegradation was closely related to their desorbed amount in 90% isopropanol solution during 24 h of contact, while the desorption of model PAH compounds from freshly spiked NY/NJH sediment did not describe the bioavailability of PAHs in the East River sediment well. The research improves our understanding of bioavailability as a controlling factor in bioremediation of PAHs and the potential of aerobic biodegradation for PAH removal and ecotoxicity reduction.

  12. Toxic effect on the rat small intestine of chronic administration of asbestos in drinking water.

    PubMed

    Delahunty, T J; Hollander, D

    1987-12-01

    Sprague-Dawley rats were given a 0.5 g/l Chrysotile asbestos solution in their drinking water (approximately 7 mg/day ingested) for 1.5 years and compared to control rats of the same age. During this time there were no differences in weight or appearance of the asbestos-treated rats in comparison to controls maintained under the same conditions. However, when in vivo intestinal permeability studies were performed using a gavage/urinary collection technique, some significant changes were noted. The recovery of lactulose in the urine of asbestos-treated rats was 0.66 +/- 0.07%, significantly less than that of the controls (1.01 +/- 0.08, P less than 0.005). The recovery of mannitol was similarly decreased (2.2 +/- 0.28 vs. 3.0 +/- 0.17, P less than 0.02), but that of rhamnose was unchanged. Creatinine clearance studies indicated that there was no impairment of kidney function in the asbestos-treated group and polarized light microscopy did not reveal any asbestos fibers in sections of the small bowel. The results suggest that the chronic exposure of rats to asbestos fibers in the drinking water results in a decreased ability of the intestine to absorb some non-metabolizable sugars. PMID:3120357

  13. Oral Toxicity Study and Skin Sensitization Test of a Cricket

    PubMed Central

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-01-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  14. Radionuclide studies of chronic schistosomal uropathy

    SciTech Connect

    Lamki, L.M.; Lamki, N.

    1981-08-01

    Fifty patients with chronic urinary tract schistosomiasis were studied with /sup 99m/Tc-DTPA. All had a flow study, sequential analog imaging, and digital imaging for 25-35 minutes (20-sec. frames). Time-activity curves (DTPA renograms) were extracted; 12 patients had /sup 131/I-Hippuran probe renograms as well. Renal changes included diminished perfusion and structural abnormalities ranging from minor calyceal dilatation to overt hydronephrosis. Ureteral changes included dilatation, tortuosity, and kinking. Marked distortion of the ureterovesical tunction was seen in some patients due to periureteral and perivesicular fibrosis, which is a major factor in upper urinary tract damage. Renograms showed varying obstruction and parenchymal damage. Nuclear medicine complements excretory urography and is sometimes preferable for visualization of the ureters. After the initial urogram, sequential DTPA scanning and renography are sufficient for follow-up.

  15. Ovarian toxicity and carcinogenicity in eight recent national toxicology program studies

    SciTech Connect

    Maronpot, R.R.

    1987-08-01

    Ovarian toxicity and/or carcinogenicity has been documented for at least eight chemicals recently tested in National Toxicity Program prechronic and chronic rodent studies. The chemicals that yielded treatment-related ovarian lesions were 1,3-butadiene, 4-vinylcyclohexene, vinylcylohexene deipoxide, nitrofurantoin, nitrofurazone, benzene, ..delta..-9-tetrahydrocannabinol, and tricresylphosphate. Typical nonneoplastic ovarian changes included hypoplasia, atrophy, follicular necrosis, and tubular hyperplasia. The most commonly observed treatment-related neoplasms were granulosa cell tumors and benign mixed tumors. A relationship between antecedent ovarian hypoplasia, atrophy, and hyperplasia and subsequent ovarian neoplasia is supported by some of these National Toxicology Program studies. Pathologic changes in other tissues such as the adrenal glands and uterus were associated with the treatment-related ovarian changes.

  16. Flavorings Boost Toxicity of E-Cigarettes in Lab Study

    MedlinePlus

    ... studies on animals often do not predict clinical effects in humans, the same is true of cell toxicity studies," Conley said. The study findings were published online recently in the journal Tobacco Control . Earlier this year, the U.S. Food and Drug Administration extended its authority over tobacco ...

  17. Ecological modelling and toxicity data coupled to assess population recovery of marine amphipod Gammarus locusta: Application to disturbance by chronic exposure to aniline.

    PubMed

    de los Santos, Carmen B; Neuparth, Teresa; Torres, Tiago; Martins, Irene; Cunha, Isabel; Sheahan, Dave; McGowan, Tom; Santos, Miguel M

    2015-06-01

    A population agent-based model of marine amphipod Gammarus locusta was designed and implemented as a basis for ecological risk assessment of chemical pollutants impairing life-history traits at the individual level. We further used the model to assess the toxic effects of aniline (a priority hazardous and noxious substance, HNS) on amphipod populations using empirically-built dose-response functions derived from a chronic bioassay that we previously performed with this species. We observed a significant toxicant-induced mortality and adverse effects in reproductive performance (reduction of newborn production) in G. locusta at the individual level. Coupling the population model with the toxicological data from the chronic bioassay allowed the projection of the ecological costs associated with exposure to aniline that might occur in wild populations. Model simulations with different scenarios indicated that even low level prolonged exposure to the HNS aniline can have significant long-term impacts on G. locusta population abundance, until the impacted population returns to undisturbed levels. This approach may be a useful complement in ecotoxicological studies of chemical pollution to transfer individual-collected data to ecological-relevant levels.

  18. Effects of erucic acid supplemented feeding on chronic doxorubucin toxicity in rats

    PubMed Central

    Bozcali, Evin; Süzer, Öner; Gürsoy, Hatice Nilüfer; Atukeren, Pinar; Gümüstas, Koray M

    2009-01-01

    One of the undesired complications of the chemotherapy with doxorubicin is cardiotoxicity. Cardiac effect of erucic acid, which is a member of omega-9 fatty acid, is investigated on doxorubicin treatment in this study. Forty-eight rats were divided into eight groups and each group contained six rats. First group rats were fed with milk. In the third and fifth groups we fed rats with milk supplemented 0.5% and 5% erucic acid respectively. The groups 2, 4, 6 were fed as the groups 1, 3, 5 respectively; we injected 2 mg/kg twice weekly intraperitoneal doxorubicin to these groups whereas we injected isovolumous normal saline to the groups 1, 3, 5. Two other groups (groups 7 and 8) were fed with standard pellet. Group 8 received 2 mg/kg doxorubicin twice weekly; group 7 received normal saline. After 4 weeks hearts were isolated and mounted on a Langendorff apparatus perfused by modified Tyrode solution. Surviving rats were significantly less in erucic acid + doxorubicin groups at the end of the treatment period (p<0.05). No significant difference was found between groups for malondialdehyde, catalase, cytochrome c oxidase and isolated heart measurements. Concomitant application of erucic acid and doxorubicin showed profound toxicity. PMID:20057977

  19. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    PubMed

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period.

  20. [Sub-chronic toxicity and test of eye irritability of leaf aqueous extract from Plantago major (plantaginaceae)].

    PubMed

    García González, Mildred; Coto Morales, Teresita; Soto Rodríguez, Gerardo A; Pazos, Liliana

    2003-01-01

    For the sub-chronic toxicity an aqueous preparation of Plantago major leaves was tested in 20 male NGP mice, with an average weight of 20.15 g and separated in two groups of ten individuals each. The dose used was 2000 mg/kg and the control group received 0.5 ml of distilled water. The extract administration was done daily during five days at week for a total period of 40 days. Signs of sub-chronic toxicity were observed in the days two and 12 of treatment. No significant change in corporal weight was observed. The ocular irritation was tested in five New Zeland male rabbits, with an average weight of 3.640 kg. The dose used was a 200 microliters the preparation (100 mg/ml) of Plantago major leaves, instill into the right eye and the control was used the left eye instill 200 microliters of distilled water. The administration was done daily during five days. The extract shows no significant irritation during the observation period. PMID:15162770

  1. Decreased renal accumulation and toxicity of a new VCM formulation in rats with chronic renal failure.

    PubMed

    Hodoshima, Naoko; Masuda, Satohiro; Inui, Ken-Ichi

    2007-12-01

    We previously reported that MEEK, a generic product of vancomycin hydrochloride (VCM), was less nephrotoxic than a conventional preparation (S-VCM) in normal rats at a nephrotoxic dose (400 mg/kg) of VCM.(1)) To infer the clinical significance of this finding, we compared the risk of nephrotoxicity of these two formulations in rats with chronic renal failure in this study. MEEK or S-VCM was given intravenously to two weeks post-5/6 nephrectomy rats, and the pharmacokinetic profile of VCM and pathological evaluation were compared. There were no differences at the daily clinical dose (40 mg/kg), but at the twice the daily clinical dose (80 mg/kg), the mean plasma concentration of VCM was higher after S-VCM administration than after MEEK and the CL(tot) and CL(r) decreased to approximately 60% of those after MEEK. The renal tissue concentration of VCM was 1.5-fold higher at 24hr after S-VCM administration than after MEEK. Pathologically, no marked differences between the findings were observed at 24hr after administration of each formulation. These findings suggest that MEEK reduces renal damage caused by VCM and prevents the iatrogenic aggravation of nephrotoxicity. These results hold out hope that MEEK will permit high-dose administration of VCM, while revealing clinical significance of the nephrotoxicity-reduction by MEEK.

  2. Two-generation reproduction toxicity study in rats with methoxychlor.

    PubMed

    Aoyama, Hiroaki; Hojo, Hitoshi; Takahashi, Ken L; Shimizu-Endo, Naoko; Araki, Masayuki; Takeuchi-Kashimoto, Yukiko; Saka, Machiko; Teramoto, Shoji

    2012-03-01

    A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

  3. Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

    PubMed Central

    Wang, Bing; Tanaka, Kaoru; Katsube, Takanori; Ninomiya, Yasuharu; Vares, Guillaume; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru

    2015-01-01

    Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. PMID:26045492

  4. Historical control data on developmental toxicity studies in rodents.

    PubMed

    Ema, Makoto; Endoh, Katsumi; Fukushima, Ryou; Fujii, Sakiko; Hara, Hiroaki; Hirata-Koizumi, Mutsuko; Hirose, Akihiko; Hojo, Hitoshi; Horimoto, Masao; Hoshino, Nobuhito; Hosokawa, Yoshinori; Imai, Yukari; Inada, Hiroshi; Inawaka, Kunifumi; Itoh, Keiichi; Katsumata, Yoshihiro; Izumi, Hiroyuki; Kato, Hirohito; Maeda, Maki; Matsumoto, Kiyoshi; Matsuo, Seiki; Matsuoka, Toshiki; Matsuura, Ikuo; Mineshima, Hiroshi; Miwa, Yoji; Nakano, Nao; Naya, Masato; Noyori, Hiroko; Ohta, Takafumi; Oku, Harutaka; Ono, Atsushi; Shimizu, Tatsuya; Shimomura, Kazuhiro; Takakura, Ikuro; Tanaka, Ryota; Tateishi, Taishi; Tominaga, Yuko; Uesugi, Tohru; Urakawa, Chizuru; Yabe, Kaoru; Yamashita, Akihito; Yamauchi, Toshiaki; Yokoi, Ryohei

    2014-08-01

    Historical control data on rodent developmental toxicity studies, performed between 1994 and 2010, were obtained from 19 laboratories in Japan, including 10 pharmaceutical and chemical companies and nine contract research organizations. Rats, mice, and hamsters were used for developmental toxicity studies. Data included maternal reproductive findings at terminal cesarean sections and fetal findings including the spontaneous incidences of external, visceral, and skeletal anomalies. No noticeable differences were observed in maternal reproductive data between laboratories. Inter-laboratory variations in the incidences of fetuses with anomalies appeared to be due to differences in the selection of observation parameters, observation criteria, classification of the findings, and terminology of fetal alterations. Historical control data are useful for the appropriate interpretation of experimental results and evaluation of the effects of chemical on reproductive and developmental toxicities. PMID:24666250

  5. Development of a chronic fish toxicity model for predicting sub-lethal NOEC values for non-polar narcotics.

    PubMed

    Austin, T J; Eadsforth, C V

    2014-01-01

    To comply with the REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) regulations, the generation of chronic fish toxicity data is required for chemicals produced or imported within or into the EU in quantities greater than 100 tonnes per year. This comes at a great cost to industry and consumers alike and requires the sacrifice of many vertebrates. In acknowledgment of these issues the REACH regulations encourage the use of non-testing methods (NTM). These include read-across, weight-of-evidence and QSAR (quantitative structure-activity relationship) techniques. There are many QSAR tools available to generate predictive values for a number of physico-chemical properties, as well as human and environmental health end points; however, close analysis of the currently available chronic fish models identified room for improvement in both the selection of data used and in its application in model creation. In light of this a model was developed using only sub-lethal no-observed-effect concentration (NOEC) end-point data according to best practice QSAR development. Only the lowest value was taken for each compound, in line with the conservative approach taken by the European Chemicals Agency (ECHA). The model developed meets the Organisation for Economic Co-operation and Development (OECD) principles, has strong internal and external validation statistics, and can reliably predict sub-lethal chronic NOEC values for fish within its defined applicability domain.

  6. Parenting in the context of chronic pain: A controlled study of parents with chronic pain

    PubMed Central

    Wilson, Anna C.; Fales, Jessica L.

    2014-01-01

    Objectives This study aims to describe what adults with chronic pain experience in their role as parents, utilizing quantitative and qualitative methods. The first aim is to compare parents with chronic pain to parents without chronic pain on perceptions of their adolescent’s pain, parental response to pain, and catastrophizing beliefs about pain. The study also examined predictors of parental protective behaviors, and examined whether these associations differed by study group. Methods Parents with chronic pain (n=58) and parents without chronic pain (n=72) participated, and completed questionnaire measures of pain characteristics and pain interference, as well as measures of parental catastrophizing and protective pain responses. Parents with chronic pain also completed a structured interview about their experience of being a parent. Interview responses were videotaped and subsequently coded for content. Results Compared to controls, parents with chronic pain endorsed more pain in their adolescents, and were more likely to catastrophize about their adolescent’s pain and respond with protective behaviors. Parent’s own pain interference and the perception of higher pain in their adolescent was associated with increased protective parenting in the chronic pain group. Qualitative coding revealed a number of areas of common impact of chronic pain on parenting. Discussion Chronic pain impacts everyday parenting activities and emotions, and impacts pain-specific parent responses that are known to be related to increased pain and pain catastrophizing in children and adolescents. Parents with chronic pain might benefit from interventions that address potential parenting difficulties, and might improve outcomes for their children. PMID:25232862

  7. Target organ profiles in toxicity studies supporting human dosing: Does severity progress with longer duration of exposure?

    PubMed

    Roberts, Ruth; Callander, Richard; Duffy, Paul; Jacobsen, Matt; Knight, Richard; Boobis, Alan

    2015-12-01

    We have previously reported the profile of target organs (defined as organs showing histopathological changes) in rodent and non-rodent toxicity studies conducted prior to first-time-in-man (FTiM) for 77 AstraZeneca candidate drugs (CDs). Here, we test the assumption that toxicity is exacerbated by dosing duration by comparing the incidence and severity of target organ toxicities in these ≤ 6 week FTiM studies with those observed in subsequent subchronic/chronic (≥ 3 month) studies. Looking at the effect of dosing duration on severity (pathological score) and incidence (percentage of animals within the group) for the 39 CDs that met the criteria for inclusion (comparable doses between FTiM and subchronic/chronic studies), new toxicities appeared for 31 target organs but existing ones resolved for 29 target organs. Increased severity was more frequent for rodent (16 target organs) than for non-rodent (4 target organs). Most notable changes were a large increase in severity/incidence in liver and in non-rodent lung in contrast to a large decrease in severity and incidence for kidneys/ureter and for the non-rodent thymus. Overall this analysis shows that, even with continued exposure, target organ toxicities of CDs are as likely to show partial or complete recovery as they are to progress in severity.

  8. Interactive toxicity of major ion salts: Comparisons among species and between acute and chronic endpoints

    EPA Science Inventory

    Increased concentrations of major ions (Na, K, Ca, Mg, Cl, SO4, HCO3) in freshwater systems can result from a variety of anthropogenic activities, and can adversely affect aquatic organisms if the increase is sufficiently severe. Laboratory tests have indicated that the toxicity...

  9. Modifying Foods and Feeding Regimes to Optimize the Performance of Hyalella azteca during Chronic Toxicity Tests

    EPA Science Inventory

    The amphipod Hyalella azteca is commonly used to assess the toxicity of sediments and waters. However, laboratories have reported varying success in maintaining healthy cultures and in obtaining consistent growth and reproduction (where applicable), especially during tests...

  10. 40 CFR 799.9430 - TSCA combined chronic toxicity/carcinogenicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... occurring as a result of prolonged action on, or increased concentration of, the administered test substance... toxic effect of the class of substances being tested, if known, and provided it does not have a... vehicles. (ii) One lot of the test substance should be used throughout the duration......

  11. Predictive Signatures from ToxCast Data for Chronic, Developmental and Reproductive Toxicity Endpoints

    EPA Science Inventory

    The EPA ToxCast program is using in vitro assay data and chemical descriptors to build predictive models for in vivo toxicity endpoints. In vitro assays measure activity of chemicals against molecular targets such as enzymes and receptors (measured in cell-free and cell-based sys...

  12. The spectrum of cutaneous and internal malignancies in chronic arsenic toxicity.

    PubMed

    Wong, S T; Chan, H L; Teo, S K

    1998-04-01

    We report 3 patients of chronic arsenic poisoning with characteristic skin changes. All 3 patients had a past history of asthma and were treated with Traditional Chinese Medication. We believe that the Chinese medications were the source of arsenic poisoning. Two of the 3 patients also had internal malignancy. The association of arsenic with internal malignancy is reviewed.

  13. A 3R compliant testing strategy to predict chronic fish toxicity

    EPA Science Inventory

    To ensure an ecologically relevant basis for environmental quality standards, whole-organism vertebrate tests are considered most suitable. Currently, the fish early life-stage (FELS) test (OECD 210), which involves an exposure up to one - two months, is used to estimate chronic ...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... relating to the chronic hazard of sensitization are discussed in 16 CFR 1500.3(c)(5).) (a) Carcinogenicity... substances or for which there is no evidence of carcinogenic effect under the following categories lack...-related increase in the incidence of malignant tumors, combined malignant and benign tumors, or...

  15. [Study on the toxicity of horseshoe crabs in mice].

    PubMed

    Liao, Y; Li, X

    2000-05-30

    In order to study the toxicity of horseshoe crabs(tachypleus tridentatus and carcinoscorpius rotundicauda) in the sea of China, the extracts of tissues from tachypleus tridentatus and carcinoscorpius rotundicauda were injected into the abdominal cavity of mice for testing their poisoning effects. The results showed that the toxicity of carcinoscorpius rotundicauda was much higher than that of tachypleus tridentatus. The length of time from the injection to the death was much shorter for Carcinoscorpius rotundicauda than that for tachypleus tridentatus. The signs before death for Carcinoscorpius rotundicauda poisoning were restless, jumping and spasm but that for Tachypleus tridentatus was lethargy. The toxicity of adult horseshoe crabs was much higher than that of young horseshoe crabs.

  16. Macrolide-induced digoxin toxicity: a population-based study.

    PubMed

    Gomes, T; Mamdani, M M; Juurlink, D N

    2009-10-01

    In this 15-year, population-based, nested case-control study, we investigated the association between hospitalization for digoxin toxicity and recent exposure to individual macrolide antibiotics. Clarithromycin was associated with the highest risk of digoxin toxicity (adjusted odds ratio (OR) 14.8; 95% confidence interval (CI) 7.9-27.9), whereas erythromycin and azithromycin were associated with much lower risk (adjusted OR 3.7; 95% CI 1.7-7.9; and adjusted OR 3.7; 95% CI 1.1-12.5, respectively). We found no increased risk with a neutral comparator, cefuroxime (adjusted OR 0.8; 95% CI 0.2-3.4).

  17. PROSPECTIVE PREGNANCY STUDY DESIGNS FOR ASSESSING REPRODUCTIVE AND DEVELOPMENTAL TOXICANTS

    EPA Science Inventory

    Prospective Pregnancy Study Designs for Assessing Reproductive and Developmental Toxicants
    Germaine M. Buck,1 Courtney D. Johnson,1 Joseph Stanford,2 Anne Sweeney,3 Laura Schieve,4 John Rockett,5 Sherry G. Selevan,6 Steve Schrader 7

    Abstract
    The origin of successfu...

  18. Malaria in cynomolgus monkeys used in toxicity studies in Japan.

    PubMed

    Ohta, Etsuko; Nagayama, Yuko; Koyama, Naoki; Kakiuchi, Dai; Hosokawa, Satoru

    2016-01-01

    Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies.

  19. Malaria in cynomolgus monkeys used in toxicity studies in Japan

    PubMed Central

    Ohta, Etsuko; Nagayama, Yuko; Koyama, Naoki; Kakiuchi, Dai; Hosokawa, Satoru

    2015-01-01

    Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies. PMID:26989299

  20. Interactions of waterborne and dietborne Pb in rainbow trout, Oncorhynchus mykiss: Bioaccumulation, physiological responses, and chronic toxicity.

    PubMed

    Alsop, Derek; Ng, Tania Y-T; Chowdhury, M Jasim; Wood, Chris M

    2016-08-01

    In Pb-contaminated environments, simultaneous exposure to both waterborne and dietborne Pb is likely to occur. This study examined the potential interactive effects of these two pathways in juvenile rainbow trout that were exposed to Pb in the water alone, in the diet alone, and in combination for 7 weeks. The highest waterborne Pb concentration tested (110μgL(-1)) was approximately equivalent to the 7-week LC20 (97μgL(-1)) measured in a separate trial, while the lowest was a concentration often measured in contaminated environments (8.5μgL(-1)). The live diet (10% daily ration on a wet mass basis) consisted of oligochaete worms (Lumbriculus variegatus) pre-exposed for 28days to the same waterborne Pb concentration, and the highest dietary dosing rate to the trout was 12.6μg Pb g fish(-1)day(-1). With waterborne exposure, whole body Pb burden increased to a greater extent in the worms than in the fish. Nonetheless, in trout waterborne exposure still resulted in 20-60-fold greater Pb accumulation compared to dietborne Pb exposure. However, combined exposure to both waterborne and dietborne Pb reduced the whole body accumulation extensively at waterborne Pb>50μgL(-1), with similar antagonistic interaction in liver and carcass (but not gill or gut) at a lower threshold of 20μgL(-1). Growth effects in trout were minimal with marginal reductions in the dietborne and combined exposures seen only at 110μgL(-1). Chronic Pb exposure reduced lipid and carbohydrates level in the worms by 50% and 80% respectively, while protein was unchanged, so growth effects in trout may have been of indirect origin. After 7 weeks, Ca(2+) homeostasis in the trout was unaffected, but there were impacts on Na(+). Blood Na(+) was reduced in waterborne and dietborne exposures, while gut Na(+)/K(+) ATPase activities were reduced in waterborne and combined exposures. This study is the first, to our knowledge to examine the interaction of waterborne and dietborne Pb exposure in fish. While

  1. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, C.-W.; James, J. T.; Taylor, L.; Zeidler-Erdely, P. C.; Castranova, V.

    2009-01-01

    NASA will build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of fine, reactive dust. Astronauts on the Moon will go in and out of the base for various activities, and will inevitably bring some dust into the living quarters. Depressurizing the airlock so that astronauts can exit for outdoor activities could also bring dust inside the airlock to the habitable area. Concerned about the potential health effects on astronauts exposed to airborne lunar dust, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust. The toxicity data also will be needed by toxicologists to establish safe exposure limits for astronauts residing in the lunar habitat and by environmental engineers to design an appropriate dust mitigation strategy. We conducted a study to examine biomarkers of toxicity (inflammation and cytotoxicity) in lung lavage fluids from mice intrapharyngeally instilled with lunar dust samples; we also collected lung tissue from the mice for histopathological examination 3 months after the dust instillation. Reference dusts (TiO2 and quartz) having known toxicities and industrial exposure limits were studied in parallel with lunar dust so that the relative toxicity of lunar dust can be determined. A 6-month histopathology study has been planned. These instillation experiments will be followed by inhalation studies, which are more labor intensive and technologically difficult. The animal inhalation studies will be conducted first with an appropriate lunar dust simulant to ensure that the exposure techniques to be used with actual lunar dust will be successful. The results of these studies collectively will reveal the toxicological risk of exposures and enable us to establish exposure limits on lunar dust for astronauts living in the lunar habitat.

  2. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  3. Toxic Effects of Chronic Mercury Exposure on the Retinal Nerve Fiber Layer and Macular and Choroidal Thickness in Industrial Mercury Battery Workers

    PubMed Central

    Ekinci, Metin; Ceylan, Erdinç; Keleş, Sadullah; Çağatay, Halil Hüseyin; Apil, Aytekin; Tanyıldız, Burak; Uludag, Gunay

    2014-01-01

    Background The aim of this study was to evaluate the toxic effects of mercury on retinal nerve fiber layer thickness (RNFLT), macular thickness (MT), and choroidal thickness (CT) by using spectral-domain optical coherence tomography (SD-OCT) in battery industry workers who had been chronically exposed to mercury. Material/Methods Battery factory workers (n=31) and healthy non-factory employee controls (n=15) participated in the study. Participants were divided into 3 groups: Group 1 (n=15) was factory workers who had worked for more than 5 years in a mercury battery factory; Group 2 (n=16) was factory worker who had worked for less than 5 years in a mercury battery factory; and Group 3 (n=15) was healthy non-employees. Systemic symptoms were recorded. Ophthalmic examination included best-corrected visual acuity test, color vision test, full ophthalmologic examination, and SD-OCT of the RNLF, macula, and choroid. To determine mercury exposure, venous blood samples were collected and mercury levels were assessed. Results In our study group the most common systemic symptoms were insomnia (67.7%) and fatigue (67.7%). There were no significant differences between Group 1 and Group 2, but there were significant differences between Group 3 and both Group 1 and Group 2 in best-corrected visual acuity values (1=2<3), color vision scores, blood mercury levels, and duration (mean ±SD, range) of mercury exposure(1>2>3). OCT values of RNFLTs, MTs, and CTs of all 3 groups were statistically different from each another (1<2<3). Conclusions SD-OCT can be useful for evaluating the toxic effects of chronic exposure to mercury. PMID:25056093

  4. Short-term methods for estimating the chronic toxicity of effluents and receiving water to marine and estuarine organisms. Second edition

    SciTech Connect

    Klemm, D.J.; Morrison, G.E.; Norberg-King, T.J.; Peltier, W.H.; Heber, M.A.

    1994-07-01

    This manual describes six short-term (one hour to nine days) estuarine and marine methods for measuring the chronic toxicity of effluents and receiving waters to five species; the sheepshead minnow, Cyprinodon variegatus; the inland silverside, Menidia beryllina; the mysid, Mysidopsis bahia; the sea urchin, Arbacia punctualata; and the red macroalga, Champia parvula. The methods include single and multiple concentration static renewal and static nonrenewal toxicity tests for effluents and receiving waters. Also included are guidelines on laboratory safety, quality assurance, facilities, and equipment and supplies; dilution water; effluent and receiving water sample collection, preservation, shipping, and holding; test conditions; toxicity test data analysis; report preparation; and organism culturing, holding, and handling.

  5. Studies of skin toxicity in vitro: dose-response studies on JB6 cells.

    PubMed

    Jain, P T; Fitzpatrick, M J; Phelps, P C; Berezesky, I K; Trump, B F

    1992-01-01

    There are many reasons for developing in vitro tests of toxicity including cost, speed, studies of mechanisms, and studies utilizing human cells and tissues. The present study focuses on the development of in vitro tests to predict in vivo toxicity by comparing them to data from the literature. A broad spectrum of model toxic compounds was evaluated for toxicity on mouse skin JB6 cells in culture. These included mercuric chloride, sodium lauryl sulfate, formaldehyde, dimethyl sulfoxide, benzoyl peroxide, and ionomycin, all of which have been proven to be positive in the Draize test or in cutaneous toxicity studies. Cell viability was evaluated every 15 min for up to 1 hr, and then after 24 hr of treatment using the Trypan Blue exclusion method; morphological changes were evaluated using phase-contrast and transmission electron microscopy. Dose- and time-dependent cell death and morphological changes were observed at concentrations ranging from 10(-14) to 10(-2) M. Arbitrary rankings were assigned based on 1) IC50 value estimated from the present data, and 2) in vivo toxicity reported in the Registry of Toxic Effects of Chemical Substances. Good correlation between in vitro and in vivo toxicity based on arbitrary rankings was observed. Thus, these findings suggest that the JB6 cell culture model can be used for predicting in vivo toxicity. In the future, it may be possible to utilize this system for the study of intracellular ionized calcium ([Ca2+]i), and the expression of oncogenes as early indicators of toxicity.

  6. ILSI/HESI Maternal Toxicity Workshop Summary: Maternal Toxicity and its Impact on Study Design and Data Interpretation

    EPA Science Inventory

    Workshops on maternal toxicity were held at the annual meetings of the Society of Toxicology, Teratology Society, and European Teratology Society in 2009. Prior to a general discussion of the issues involved with maternal toxicity and its impact on study design and data interpret...

  7. Denver Potable Water Reuse Demonstration Project: comprehensive chronic rat study.

    PubMed

    Condie, L W; Lauer, W C; Wolfe, G W; Czeh, E T; Burns, J M

    1994-11-01

    The health effects testing program for the Denver Water Department's Potable Water Reuse Demonstration Project was designed to evaluate the relative health effects of highly treated reclaimed water derived from secondary wastewater in comparison with Denver's present high-quality drinking water. The 1 x 10(6) gal/day treatment plant provided 500-fold concentrates of water that had been treated by multiple processes to remove microbial and chemical contaminants. Fischer 344 rats were exposed to the complex mixture solutions for up to 2 yr to evaluate chronic toxicity and oncogenicity effects. The following parameters were evaluated: clinical observations, survival rate, growth, food and water consumption, haematology, clinical chemistry, urinalysis, organ weights, gross autopsy and histopathological examination of all lesions, major tissues and organs. Clinical pathology, gross pathology, and microscopic pathology conducted at wk 26 and 65 and at the end of the study did not reveal any findings that could be considered to be treatment related. Administration of drinking water concentrates at up to 500 times the original concentration in the original water samples to F344 rats for up to 104 wk did not result in any overt toxicological or carcinogenic effects. PMID:7959456

  8. Study of splenic irradiation in chronic lymphocytic leukemia

    SciTech Connect

    Guiney, M.J.; Liew, K.H.; Quong, G.G.; Cooper, I.A.

    1989-01-01

    A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

  9. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia

    PubMed Central

    Falchi, Lorenzo; Baron, Jessica M.; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs. PMID:26977270

  10. In vivo toxicity studies of europium hydroxide nanorods in mice

    SciTech Connect

    Patra, Chitta Ranjan Abdel Moneim, Soha S.; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H.; Mukhopadhyay, Debabrata

    2009-10-01

    Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu{sup III}(OH){sub 3}] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg{sup -1} day{sup -1}) and time dependent manner (8-60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.

  11. Developing acute-to-chronic toxicity ratios for lead, cadmium, and zinc using rainbow trout, a mayfly, and a midge

    USGS Publications Warehouse

    Mebane, C.A.; Hennessy, D.P.; Dillon, F.S.

    2008-01-01

    In order to estimate acute-to-chronic toxicity ratios (ACRs) relevant to a coldwater stream community, we exposed rainbow trout (Oncorhynchus mykiss) to cadmium (Cd), lead (Pb), and zinc (Zn) in 96-h acute and 60+ day early-life stage (ELS) exposures. We also tested the acute and sublethal responses of a mayfly (Baetis tricaudatus) and a midge (Chironomus dilutus, formerly C. tentans) with Pb. We examine the statistical interpretation of test endpoints and the acute-to-chronic ratio concept. Increasing the number of control replicates by 2 to 3x decreased the minimum detectable differences by almost half. Pb ACR estimates mostly increased with increasing acute resistance of the organisms (rainbow trout ACRs

  12. Metabolomics and its application to studying metal toxicity.

    PubMed

    Booth, Sean C; Workentine, Matthew L; Weljie, Aalim M; Turner, Raymond J

    2011-11-01

    Here we explain the omics approach of metabolomics and how it can be applied to study a physiological response to toxic metal exposure. This review aims to educate the metallomics field to the tool of metabolomics. Metabolomics is becoming an increasingly used tool to compare natural and challenged states of various organisms, from disease states in humans to toxin exposure to environmental systems. This approach is key to understanding and identifying the cellular or biochemical targets of metals and the underlying physiological response. Metabolomics steps are described and overviews of its application to metal toxicity to organisms are given. As this approach is very new there are yet only a small number of total studies and therefore only a brief overview of some metal metabolomics studies is described. A frank critical evaluation of the approach is given to provide newcomers to the method a clear idea of the challenges and the rewards of applying metabolomics to their research.

  13. Clinical pathology testing recommendations for nonclinical toxicity and safety studies. AACC-DACC/ASVCP Joint Task Force.

    PubMed

    Weingand, K; Bloom, J; Carakostas, M; Hall, R; Helfrich, M; Latimer, K; Levine, B; Neptun, D; Rebar, A; Stitzel, K

    1992-01-01

    Clinical pathology testing in nonclinical toxicity and safety studies is an important part of safety assessment. In recent years, clinical laboratory testing has rapidly expanded and improved. Some government regulatory agencies provide guidelines for clinical pathology testing in nonclinical toxicity and safety studies. To improve these testing guidelines and the resultant safety assessments, the American Association for Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society for Veterinary Clinical Pathology formed a joint committee to provide expert recommendations for clinical pathology testing of laboratory species involved in subchronic and chronic nonclinical toxicity and safety studies. These recommendations include technical recommendations on blood collection techniques and hematology, serum chemistry, and urinalysis tests. PMID:1296288

  14. Improved chronic fatigue symptoms after removal of mercury in patient with increased mercury concentration in hair toxic mineral assay: a case.

    PubMed

    Shin, Sae-Ron; Han, A-Lum

    2012-09-01

    Clinical manifestations of chronic exposure to organic mercury usually have a gradual onset. As the primary target is the nervous system, chronic mercury exposure can cause symptoms such as fatigue, weakness, headache, and poor recall and concentration. In severe cases chronic exposure leads to intellectual deterioration and neurologic abnormality. Recent outbreaks of bovine spongiform encephalopathy and pathogenic avian influenza have increased fish consumption in Korea. Methyl-mercury, a type of organic mercury, is present in higher than normal ranges in the general Korean population. When we examine a patient with chronic fatigue, we assess his/her methyl-mercury concentrations in the body if environmental exposure such as excessive fish consumption is suspected. In the current case, we learned the patient had consumed many slices of raw tuna and was initially diagnosed with chronic fatigue syndrome. Therefore, we suspected that he was exposured to methyl-mercury and that the mercury concentration in his hair would be below the poisoning level identified by World Health Organization but above the normal range according to hair toxic mineral assay. Our patient's toxic chronic fatigue symptoms improved after he was given mercury removal therapy, indicating that he was correctly diagnosed with chronic exposure to organic mercury. PMID:23115707

  15. Development of Alternatives to Chronic Ecotoxicity Tests: Predicting Early-life Stage and Endocrine-mediated Toxicity in Aquatic Vertebrate Species

    EPA Science Inventory

    In June 2010, the ILSI Health and Environmental Sciences Institute (HESI) with support from sanofi-aventis, NC3Rs, the Humane Society, L’Oreal, and ECVAM, held a workshop aimed at examining critical science needs related to the development of alternatives to chronic fish toxicity...

  16. SHORT-TERM METHODS FOR ESTIMATING THE CHRONIC TOXICITY OF EFFLUENTS AND RECEIVING WATERS TO WEST COAST MARINE AND ESTUARINE ORGANISMS

    EPA Science Inventory

    This manual describes six short-term (forty minutes to seven days) estuarine and marine methods for measuring the chronic toxicity of effluents and receiving waters to eight species: the topsmelt, Atherinops affinis; the mysid, Holmesimysis costata; the sea urchin, Stronglocentro...

  17. Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

    PubMed Central

    Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

    2015-01-01

    Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

  18. A new methyl bromide gas generator for inhalation toxicity studies.

    PubMed

    Hori, H; Hyakudo, T; Tanaka, I

    1992-09-01

    A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

  19. Toxicity study of isolated polypeptide from wool hydrolysate.

    PubMed

    Li, Jiashen; Li, Yi; Zhang, Yu; Liu, Xuan; Zhao, Zheng; Zhang, Jing; Han, Yanxia; Zhou, Dangxia

    2013-07-01

    The cytotoxicity of wool polypeptide has been evaluated by both cell and animal models. Wool was dissolved in sodium hydroxide solution, the pH value of the solution was adjusted to 5.55 and the precipitate was harvested as wool polypeptide. The spray-dried polypeptide was collected as powders and characterized by SEM, FTIR and TG-DSC. The cell culturing results showed that wool polypeptide had no obvious negative effect on cell viability in vitro. Both acute oral toxicity and subacute 30-day oral toxicology studies showed that wool polypeptide had no influence on body weight, feed consumption, blood chemistry, and hematology at any dose levels. There were no treatment related findings on gross or detailed necroscopy, organ weights, organ/body weight ratios and histology. Our study indicated the absence of toxicity in wool polypeptide and supported its safe use as a food ingredient or drug carrier.

  20. Toxicity study of isolated polypeptide from wool hydrolysate.

    PubMed

    Li, Jiashen; Li, Yi; Zhang, Yu; Liu, Xuan; Zhao, Zheng; Zhang, Jing; Han, Yanxia; Zhou, Dangxia

    2013-07-01

    The cytotoxicity of wool polypeptide has been evaluated by both cell and animal models. Wool was dissolved in sodium hydroxide solution, the pH value of the solution was adjusted to 5.55 and the precipitate was harvested as wool polypeptide. The spray-dried polypeptide was collected as powders and characterized by SEM, FTIR and TG-DSC. The cell culturing results showed that wool polypeptide had no obvious negative effect on cell viability in vitro. Both acute oral toxicity and subacute 30-day oral toxicology studies showed that wool polypeptide had no influence on body weight, feed consumption, blood chemistry, and hematology at any dose levels. There were no treatment related findings on gross or detailed necroscopy, organ weights, organ/body weight ratios and histology. Our study indicated the absence of toxicity in wool polypeptide and supported its safe use as a food ingredient or drug carrier. PMID:23597444

  1. Toxicity and endocrine disruption in zebrafish (Danio rerio) and two freshwater invertebrates (Daphnia magna and Moina macrocopa) after chronic exposure to mefenamic acid.

    PubMed

    Collard, Hyo-rin Jung; Ji, Kyunghee; Lee, Sangwoo; Liu, Xiaoshan; Kang, Sungeun; Kho, Younglim; Ahn, Byeongwoo; Ryu, Jisung; Lee, Jaean; Choi, Kyungho

    2013-08-01

    Pharmaceuticals have been frequently detected in the aquatic environment. Their potential effects on the endocrine system in wildlife are of special concern because these alterations could lead to impaired reproduction. We evaluated ecotoxicities associated with long-term exposure to mefenamic acid (MFA) and potential endocrine disruption. For this purpose, acute and chronic toxicities of MFA on several aquatic organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and a teleost, Danio rerio were evaluated. The 48 h acute median effective concentration (EC50) of D. magna and M. macrocopa was 17.16 mg/L and 2.93 mg/L, respectively. In chronic toxicity test, D. magna and M. macrocopa showed significant changes in reproduction (number of young per adult) after the exposure to 1.0 mg/L and 0.25 mg/L MFA, respectively. In early life stage exposure using D. rerio, significant decrease of larval survival was observed at 1 mg/L. Changes in vitellogenin (VTG) protein concentrations in 32 day post fertilization fish and vtgI mRNA expression in adult male fish suggest endocrine disruption potentials of MFA. Among the genes of hypothalamus-pituitary-gonad axis, transcriptions of gnrh, gnrhr, cyp19a, and cyp19b increased, supporting estrogenic potential of MFA. Along with histological changes in ovaries, the results of this study provide evidences of endocrine disruption capacity of MFA. However, the effective concentrations are orders of magnitude greater than those occurring in the ambient aquatic environment. PMID:23725676

  2. The acute and chronic toxicity of cadmium and zinc to two hydra species.

    PubMed

    Holdway, D A; Lok, K; Semaan, M

    2001-01-01

    The potential of two hydra species, Hydra vulgaris (pink) and Hydra viridissima (green), for use as invertebrate models for toxicity testing of waterborne metals was investigated. The acute and subchronic toxicities of cadmium (a nonessential metal) and zinc (an essential metal) were determined. Results showed that both the hydra species were more sensitive to cadmium than to zinc, and that green hydra were more sensitive than pink hydra. The mean (SE) 96 h LC50 values of cadmium and zinc for pink hydra were 83 (8.5) and 2300 (150) micrograms/L, respectively. For green hydra, the respective 96 h LC50 values for cadmium and zinc were 3.0 (0.0) and 935 (46.5) micrograms/L. The respective 7-day no-observed-effect-concentrations (NOEC) and lowest-observed-effect-concentrations (LOEC) for pink hydra were < 13 and 13 micrograms/L for cadmium, and < 250 and 250 micrograms/L for zinc. The respective 7-day NOEC and LOEC values for green hydra were 0.4 and 0.8, microgram/L for cadmium, and 38 and 75 micrograms/L for zinc. Neither 1, 2, or 3 x 90-min pulse-exposures to 0.4, 0.8, or 1.5 micrograms/L of cadmium had any significant deleterious effect on total green hydra numbers after seven days in clean water. Green hydra appeared to be excellent freshwater invertebrate models for testing dissolved metals based on their sensitivity and the ability to rapidly assess population reproduction in the laboratory.

  3. Multiple Air-Toxics Exposure Study Working Paper Number 3. Urban air-toxics exposure model: development and application

    SciTech Connect

    Not Available

    1988-11-01

    The South Coast Air Quality Management District of California completed a Multiple Air Toxics Exposure Study (MATES) that examines the additive risk from a number of air toxics on an urban area. The project, though partially funded by EPA, is an example of how a State or local agency may approach assessing their local air-toxics risks as is encouraged by EPA's Urban Air Toxics Program which results from EPA's Air Toxic Strategy. The report is a summary of the methods used by the California agency. Though not intended as an endorsement of the entire contents of the report, EPA is reproducing their report (Working Paper Number 3) to benefit and encourage other agencies that may be contemplating such an assessment.

  4. Acute and chronic toxicity of tetrabromobisphenol A to three aquatic species under different pH conditions.

    PubMed

    He, Qun; Wang, Xinghao; Sun, Ping; Wang, Zunyao; Wang, Liansheng

    2015-07-01

    Tetrabromobisphenol A (TBBPA) is a well-known brominated flame retardant. It has been detected in the environment and shows high acute toxicity to different organisms at high concentrations. In this work, the effects of pH and dimethyl sulfoxide (DMSO) on the acute toxicity of TBBPA to Daphnia magna and Limnodrilus hoffmeisteri were tested, and the oxidative stress induced by TBBPA in livers of Carassius auratus was assessed using four biomarkers. The integrated biomarker response (IBR) was applied to assess the overall antioxidant status in fish livers. Moreover, fish tissues (gills and livers) were also studied histologically. The results showed that low pH and DMSO enhanced the toxicity of TBBPA. Furthermore, changes in the activity of antioxidant enzymes and glutathione level suggested that TBBPA generates oxidative stress in fish livers. The IBR index revealed that fish exposed to 3mg/L TBBPA experienced more serious oxidative stress than exposed to acidic or alkaline conditions. The histopathological analysis revealed lesions caused by TBBPA. This study provides valuable toxicological information of TBBPA and will facilitate a deeper understanding on its potential toxicity in realistic aquatic environments. PMID:25980965

  5. Acute and chronic toxicity of tetrabromobisphenol A to three aquatic species under different pH conditions.

    PubMed

    He, Qun; Wang, Xinghao; Sun, Ping; Wang, Zunyao; Wang, Liansheng

    2015-07-01

    Tetrabromobisphenol A (TBBPA) is a well-known brominated flame retardant. It has been detected in the environment and shows high acute toxicity to different organisms at high concentrations. In this work, the effects of pH and dimethyl sulfoxide (DMSO) on the acute toxicity of TBBPA to Daphnia magna and Limnodrilus hoffmeisteri were tested, and the oxidative stress induced by TBBPA in livers of Carassius auratus was assessed using four biomarkers. The integrated biomarker response (IBR) was applied to assess the overall antioxidant status in fish livers. Moreover, fish tissues (gills and livers) were also studied histologically. The results showed that low pH and DMSO enhanced the toxicity of TBBPA. Furthermore, changes in the activity of antioxidant enzymes and glutathione level suggested that TBBPA generates oxidative stress in fish livers. The IBR index revealed that fish exposed to 3mg/L TBBPA experienced more serious oxidative stress than exposed to acidic or alkaline conditions. The histopathological analysis revealed lesions caused by TBBPA. This study provides valuable toxicological information of TBBPA and will facilitate a deeper understanding on its potential toxicity in realistic aquatic environments.

  6. N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice.

    PubMed

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

    2016-06-01

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

  7. Aliskiren Prevents the Toxic Effects of Peritoneal Dialysis Fluids during Chronic Dialysis in Rats

    PubMed Central

    Pérez-Martínez, Juan; Pérez-Martínez, Francisco C.; Carrión, Blanca; Masiá, Jesús; Ortega, Agustín; Simarro, Esther; Nam-Cha, Syong H.; Ceña, Valentín

    2012-01-01

    The benefits of long-term peritoneal dialysis (PD) in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS) in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs) increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs. PMID:22558414

  8. Acute and sub-chronic (28 days) oral toxicity evaluation of tincture Baccharis trimera (Less) Backer in male and female rodent animals.

    PubMed

    da Silva, Andreia R H; Reginato, Fernanda Z; Guex, Camille G; Figueredo, Kássia C; da C Araldi, Isabel C; de Freitas, Robson B; Boligon, Aline A; Athayde, Margareth L; Mazzanti, Cinthia Melazzo de Andrade; Hübscher, Gilberti H; de F Bauermann, Liliane

    2016-02-01

    The infusion of Baccharis trimera (Less) DC, popularly known as "carqueja" (broom), is popularly used in the treatment of hepatic and digestive problems. In this study, we evaluated the acute and sub-chronic oral toxicities of B. trimera tincture on male and female Wistar rats according to Organization for Economic Cooperation and Development (OECD, guidelines 423 e 407, respectively). The B. trimera tincture was administered by oral gavage in a single dose (2000 mg/kg) in doses of 100, 200 and 400 mg/kg daily for 28 days. Blood was collected to analyze hematological and biochemical parameters. Kidneys and liver were homogenized to determine lipid peroxidation and δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) enzyme activities. In acute treatment, tincture did not induce any signs of toxicity or mortality. Daily oral administration produced no significant changes in the hematological and biochemical parameters, except for the hepatic enzymes alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) that showed a reduction in both sexes. Moreover, the B. trimera tincture did not increase lipid peroxidation or affected ALA-D and CAT activities. In conclusion, the tincture of B. trimera may be considered relatively safe in this protocol.

  9. Metabonomic analysis of quercetin against the toxicity of chronic exposure to low-level dichlorvos in rats via ultra-performance liquid chromatography-mass spectrometry.

    PubMed

    Wang, Hong; Li, Sifan; Qi, Lei; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhao, Xiujuan; Sun, Changhao

    2014-03-01

    This study aims to determine whether quercetin elicits a protective effect against the toxicity of chronic exposure to low-level DDVP using metabonomic technology. Rats were randomly assigned into the control, DDVP-treated, quercetin-treated, and quercetin plus DDVP-treated groups. DDVP and quercetin were given to rats daily via drinking water and gavage respectively for 90 days. Eighteen metabolites, including the biomarkers of DDVP exposure (dimethyl phosphate, DMP) and quercetin exposure (quercetin and isorhamnetina), were identified from the metabonomic profiles of rat urine using ultra-performance liquid chromatography-mass spectrometry. Compared with the control group, the DDVP-treated group showed statistically significantly increased intensities of indoxyl sulfate, estrone sulfate, cholic acid, deoxycholic acid, p-cresol, p-cresol sulfate, and orotic acid but decreased intensities of suberic acid, citric acid, sebacic acid, hippuric acid, taurine, phosphocreatine, 3-hydroxyanthranilic acid, and kynurenic acid. The tendency of the aforesaid metabolites to change was significantly ameliorated in the quercetin (50mg/kg·bw) plus DDVP (7.2mg/kg·bw)-treated group compared with the DDVP-treated group. However, the levels of these metabolites in the quercetin plus DDVP-treated groups were still significantly different from those of the control group. These results indicate that quercetin has a partial protective effect on DDVP-induced toxicity.

  10. Comparing disproportionate exposure to acute and chronic pollution risks: a case study in Houston, Texas.

    PubMed

    Chakraborty, Jayajit; Collins, Timothy W; Grineski, Sara E; Montgomery, Marilyn C; Hernandez, Maricarmen

    2014-11-01

    While environmental justice (EJ) research in the United States has focused primarily on the social distribution of chronic pollution risks, previous empirical studies have not analyzed disparities in exposure to both chronic (long-term) and acute (short-term) pollution in the same study area. Our article addresses this limitation though a case study that compares social inequities in exposure to chronic and acute pollution risks in the Greater Houston Metropolitan Statistical Area, Texas. The study integrates estimates of chronic cancer risk associated with ambient exposure to hazardous air pollutants from the Environmental Protection Agency's National-Scale Air Toxics Assessment (2005), hazardous chemical accidents from the National Response Center's Emergency Response Notification System (2007-2011), and sociodemographic characteristics from the American Community Survey (2007-2011). Statistical analyses are based on descriptive comparisons, bivariate correlations, and locally derived spatial regression models that account for spatial dependence in the data. Results indicate that neighborhoods with a higher percentage of Hispanic residents, lower percentage of homeowners, and higher income inequality are facing significantly greater exposure to both chronic and acute pollution risks. The non-Hispanic black percentage is significantly higher in neighborhoods with greater chronic cancer risk, but lower in areas exposed to acute pollution events. Households isolated by language--those highly likely to face evacuation problems during an actual chemical disaster--tend to reside in areas facing significantly greater exposure to high-impact acute events. Our findings emphasize the growing need to examine social inequities in exposure to both chronic and acute pollution risks in future EJ research and policy.

  11. Chronic toxicity bioassay and effect of endosulfan, HCH, copper and zinc on the survival and intermoult duration of larvae of mangrove crab Macrophthalmus erato De Man.

    PubMed

    Kannupandi, T; Pasupathi, K; Soundarapandian, P

    2001-08-01

    The effects of insecticides (endosulfan, HCH) and heavy metals (copper and zinc) were studied on survival and duration of the moult cycle of larvae and megalopa of a common mangrove crab, Macrophthalmus erato, that inhabits Pitchavaram mangroves, southeast coast of India. In chronic toxicity test, percentage of survival from hatchling to megalopa stage at different concentrations of endosulfan (0.048 to 0.36 microg/L), HCH (0.32 to 2.4 microg/L), copper (9.0 to 67.5 microg/L) and zinc (15.2 to 139.0 microg/L) were 6, 12, 8 and 12 respectively. Endosulfan, HCH, copper and zinc considerably increased the total period in development from first zoea to megalopa stage from 18 days in the control to 23, 21, 20 and 22 days in the treated specimens. It is concluded that concentrations well below the observed chronic concentrations, may prove to be more deleterious to larva of this species in natural environment leading to reduction in the success of recruitment to the adult population. PMID:12018587

  12. Histopathology of Incidental Findings in Beagles Used in Toxicity Studies

    PubMed Central

    Sato, Junko; Doi, Takuya; Wako, Yumi; Hamamura, Masao; Kanno, Takeshi; Tsuchitani, Minoru; Narama, Isao

    2012-01-01

    The purpose of our publication is to widely communicate the pictures of spontaneous findings occurring in beagles. Spontaneous arteritis occurs commonly in beagles. Frequent sites of arteritis are the heart, spleen, pancreas, epididymis and spinal cord. Morphological similarities between spontaneous and drug-induced arterial lesions may cause confusion when evaluating vascular toxicity of chemicals such as vasodilating agents. Focal and minimal inflammatory lesions are occasionally seen in the lung and may be associated with aspiration of food particles or of unknown causes. A cystic change with copious mucin production occurs occasionally in the mucosal epithelium of the gall bladder. Nesidioblastosis is seen rarely in the pancreas of beagles. C-cell complex and lymphocytic thyroiditis are common thyroid lesions. Spontaneous focal hypospermatogenesis and lobular Sertoli-cell-only seminiferous tubules occurring frequently in beagles must be distinguished from drug-induced damage of the seminiferous tubules in toxicity studies. The morphological differences of the female genital system in each cycle need to be understood; therefore, we present the normal features of the cyclic changes of the female genital organs. Further, we provide more information on spontaneous findings in beagles for exact diagnoses in toxicity studies. PMID:22481862

  13. SAR STUDY OF NASAL TOXICITY: LESSONS FOR MODELING SMALL TOXICITY DATASETS

    EPA Science Inventory

    Most toxicity data, particularly from whole animal bioassays, are generated without the needs or capabilities of structure-activity relationship (SAR) modeling in mind. Some toxicity endpoints have been of sufficient regulatory concern to warrant large scale testing efforts (e.g....

  14. Experimental studies of chronic pneumonia of sheep.

    PubMed

    Gilmour, J S; Jones, G E; Rae, A G

    1979-01-01

    Strains of Mycoplasma ovipneumoniae and Pasteurella haemolytica isolated from sheep affected with chronic pneumonia were inoculated by endobronchial route to conventionally-reared and SPF (Specific Pathogen-Free) lambs. Changes resembling those of the naturally-occurring disease were produced in most lambs given the organisms in combination and in some given M. ovipneumoniae alone. Similar but less extensive changes were seen in SPF lambs and fewer animals were affected. Different strains of M. ovipneumoniae did not affect the extent of changes produced in SPF lambs. M. ovipneumoniae became established in the lungs of both types of sheep; P. haemolytica did so less readily. It was concluded that chronic pneumonia may be reproduced in conventional animals by combined inoculation of M. ovipneumoniae and P. haemolytica. Age and status of immunity to mycoplasmas may account for the different responses of conventional and SPF lambs.

  15. Review of toxicity studies performed on an underground coal gasification condensate water

    SciTech Connect

    Barker, F.P.

    1987-09-01

    Three studies related to the toxicity of underground coal gasification (UCG) waters have bee conducted: (1) toxicity study of UCG water and its fractions as determined by the Microtox test, (2) toxicity study of biotreated UCG water as determined by the Microtox test, and (3) toxicity study of UCG water to macroinvertebrates. The results of these studies are summarized herein. The gas condensate water from the UCG process is extremely toxic as determined by assays with photoluminescent bacteria (Microtox), benthic (bottom-dwelling) macroinvertebrates (mayflies), and Daphnia magna (water flea). Microtox bioassays reveal that the toxic components of the water reside in both the organophilic and hydrophilic fractions, although the organophilic fraction is notably more toxic. A sequential treatment process reduced the toxicity of the UCG water, as measured by the Microtox test. Solvent extraction (to remove phenols) followed by ammonia stripping yielded a less toxic water. Additional treatment by activated sludge further reduced toxicity. Finally, the addition of powdered activated carbon to the activated sludge yielded the least toxic water. A bioassay technique was developed for lotic (running water) macroinvertebrates (Drunella doddsi and Iron longimanus). The toxicity results were compared with results from the traditional test animal, Daphnia magna. Short-term exposures to the UCG waters were more toxic to Daphnia magna than to Drunella doddsi or Iron longimanus, although the toxicity values begin to merge with longer test exposure. The greater toxicity seems to be related to a thinner exoskeleton. 26 refs., 2 figs., 6 tabs.

  16. Liver structural alterations accompanying chronic toxicity in fishes: Potential biomarkers of exposure

    SciTech Connect

    Hinton, D.E.; Lauren, D.J. ); Holliday, T.L. ); Giam, C.S. )

    1988-09-01

    Hepatic neoplasms in fish involve hepatocytes, biliary epithelial cells and possibly perisinusoidal and endothelial cells. The application of this spectrum of hepatic alterations as biomarkers for field investigations will be proposed. Alternations in livers of sea pen cultured salmonids will be reviewed as an in situ verification of the validity of liver responses. Observations in livers of mature, moribund striped bass from the Carquinez Strait die-off will be reviewed as an example of hepatotoxicity in lethally injured feral fish. Confounding alterations associated with infectious disease including parasites will be compared using results obtained from recent survey of fishes of the Kanawha River, a heavily industrialized stream in West Virginia. Practical morphometric approaches designed to evaluate stress-related alterations in livers and their relation to assay of feral fishes will be presented. Histologic, progressive responses in a carcinogen resistant and a carcinogen responsive species will be presented and discussed as one means to determine toxic, but not necessarily neoplastic, alternations in livers of impacted organisms.

  17. Acute and chronic toxicity of the new explosive CL-20 to the earthworm (Eisenia andrei) exposed to amended natural soils.

    PubMed

    Robidoux, Pierre Yves; Sunahara, Geoffrey I; Savard, Kathleen; Berthelot, Yann; Dodard, Sabine; Martel, Majorie; Gong, Ping; Hawari, Jalal

    2004-04-01

    Monocyclic nitramine explosives such as 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are toxic to a number of ecological receptors, including earthworms. The polycyclic nitramine CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane) is a powerful explosive that may replace RDX and HMX, but its toxicity is not known. In the present study, the lethal and sublethal toxicities of CL-20 to the earthworm (Eisenia andrei) are evaluated. Two natural soils, a natural sandy forest soil (designated RacFor2002) taken in the Montreal area (QC, Canada; 20% organic carbon, pH 7.2) and a Sassafras sandy loam soil (SSL) taken on the property of U.S. Army Aberdeen Proving Ground (Edgewood, MD, USA; 0.33% organic carbon, pH 5.1), were used. Results showed that CL-20 was not lethal at concentrations of 125 mg/kg or less in the RacFor2002 soil but was lethal at concentrations of 90.7 mg/kg or greater in the SSL soil. Effects on the reproduction parameters such as a decrease in the number of juveniles after 56 d of exposure were observed at the initial CL-20 concentration of 1.6 mg/kg or greater in the RacFor2002 soil, compared to 0.2 mg/kg or greater in the SSL soil. Moreover, low concentrations of CL-20 in SSL soil (approximately 0.1 mg/kg; nominal concentration) were found to reduce the fertility of earthworms. Taken together, the present results show that CL-20 is a reproductive toxicant to the earthworm, with lethal effects at higher concentrations. Its toxicity can be decreased in soils favoring CL-20 adsorption (high organic carbon content).

  18. Acute and chronic toxicity of the new explosive CL-20 to the earthworm (Eisenia andrei) exposed to amended natural soils.

    PubMed

    Robidoux, Pierre Yves; Sunahara, Geoffrey I; Savard, Kathleen; Berthelot, Yann; Dodard, Sabine; Martel, Majorie; Gong, Ping; Hawari, Jalal

    2004-04-01

    Monocyclic nitramine explosives such as 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are toxic to a number of ecological receptors, including earthworms. The polycyclic nitramine CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane) is a powerful explosive that may replace RDX and HMX, but its toxicity is not known. In the present study, the lethal and sublethal toxicities of CL-20 to the earthworm (Eisenia andrei) are evaluated. Two natural soils, a natural sandy forest soil (designated RacFor2002) taken in the Montreal area (QC, Canada; 20% organic carbon, pH 7.2) and a Sassafras sandy loam soil (SSL) taken on the property of U.S. Army Aberdeen Proving Ground (Edgewood, MD, USA; 0.33% organic carbon, pH 5.1), were used. Results showed that CL-20 was not lethal at concentrations of 125 mg/kg or less in the RacFor2002 soil but was lethal at concentrations of 90.7 mg/kg or greater in the SSL soil. Effects on the reproduction parameters such as a decrease in the number of juveniles after 56 d of exposure were observed at the initial CL-20 concentration of 1.6 mg/kg or greater in the RacFor2002 soil, compared to 0.2 mg/kg or greater in the SSL soil. Moreover, low concentrations of CL-20 in SSL soil (approximately 0.1 mg/kg; nominal concentration) were found to reduce the fertility of earthworms. Taken together, the present results show that CL-20 is a reproductive toxicant to the earthworm, with lethal effects at higher concentrations. Its toxicity can be decreased in soils favoring CL-20 adsorption (high organic carbon content). PMID:15095901

  19. A 13-week toxicity study of acrylamide administered in drinking water to hamsters.

    PubMed

    Imai, Toshio; Kitahashi, Tsukasa

    2014-01-01

    Acrylamide (AA) is known to induce tumors in various organs/tissues in rats and mice. Epidemiological studies of oral exposure have generated controversial results but mortality studies of people who work with AA have indicated increased rates of pancreatic cancer. In the present study, for dose selection for chronic toxicity/carcinogenicity studies, 13-week toxicity of AA was evaluated in Syrian hamsters, which are sensitive to induction of pancreatic ductal carcinogenesis, at concentrations required to provide doses of 0 (control), 20, 30 and 50 mg kg(-1) body weight in drinking water. Treatment with AA caused abnormal gait advancing to hind limb paralysis in all males and females at 50 mg kg(-1). Body weights in 30 and 50 mg kg(-1) males and 50 mg kg(-1) females were lower than in the controls. At termination of the study, red blood cells (RBC) and hemoglobin (Hb) were decreased or showed a tendency for a decrease at 20 and 30 mg kg(-1) in females. Microscopically, axonal/myelin degeneration of sciatic nerves was observed in all AA-treated groups with dose dependence. No obvious changes were found in pancreatic ducts/ductules in any groups of animal. These results indicated the maximum tolerated dose for long-term studies of AA to be 20 mg kg(-1) or less in both male and female Syrian hamsters.

  20. An amphibian model for studies of developmental reproductive toxicity.

    PubMed

    Berg, Cecilia

    2012-01-01

    The developmental programming of the reproductive system is vulnerable to chemical exposure. It is therefore important to evaluate long-term consequences of early life-stage exposure to endocrine disrupting chemicals. The African clawed frog Xenopus tropicalis has several characteristics which facilitates studies of developmental reproductive toxicity. Here, I present a X. tropicalis test protocol, including study design, exposure regime, and endpoints for chemical disruption of sex differentiation, reproductive organ development, the thyroxin-regulated metamorphosis, oestrogen synthesis (activity of the CYP19 aromatase enzyme), and fertility. PMID:22669660

  1. Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys.

    PubMed

    Lacy, S A; Hitchcock, M J; Lee, W A; Tellier, P; Cundy, K C

    1998-08-01

    In animals and humans, intravenous administration of the antiviral nucleotide analogue cidofovir results in a dose-limiting nephrotoxicity characterized by damage to the proximal tubular epithelial cells. Probenecid, a competitive inhibitor of organic anion transport in the proximal tubular epithelial cells, was evaluated for its effect on the chronic toxicity and pharmacokinetics of cidofovir. Cynomolgus monkeys (5/sex/group) received cidofovir for 52 consecutive weeks as a once weekly intravenous bolus injection at 0 (saline), 0.1, 0.5, or 2.5 mg/kg/dose alone or at 2.5 mg/kg/dose in combination with probenecid (30 mg/kg/dose via oral gavage 1 h prior to cidofovir administration). Cidofovir-associated histopathological changes were seen only in the kidneys, testes, and epididymides. Nephrotoxicity (mild to moderate cortical tubular epithelial cell karyomegaly, tubular dilation, basement membrane thickening) was present only in monkeys receiving 2.5 mg/kg/dose cidofovir without probenecid. The incidence and severity of testicular (hypo- and aspermatogenesis) and epididymal (severe oligo- and aspermia) changes were increased in monkeys administered cidofovir at 2.5 mg/kg/dose, either alone or in combination with oral probenecid. Renal drug clearance was decreased between Weeks 1 and 52 in the 2.5 mg/kg/dose groups and resulted in an increased systemic exposure to cidofovir (as measured by AUC) that was significantly greater in monkeys administered cidofovir alone (312% increase in males, 98% in females) than in those coadministered probenecid (32% increase in males, 3% in females). These results demonstrate that oral probenecid coadministration protects against the morphological evidence of nephrotoxicity and the accompanying decrease in renal clearance in monkeys receiving chronic intravenous cidofovir treatment.

  2. Reproductive toxicity of chronic lead exposure in male and female mice.

    PubMed

    Pinon-Lataillade, G; Thoreux-Manlay, A; Coffigny, H; Masse, R; Soufir, J C

    1995-11-01

    The reproductive toxicity of lead was investigated in NMRI mice exposed to 0.5% lead acetate in drinking water from day 1 of intra-uterine life until 60 days after birth. Compared with control mice, the weights of lead-exposed fetuses and subsequently of the lead-exposed weaned pups, male and female, diminished by 11 and 13% respectively. The lead-exposed male and female offspring of lead-exposed dams were mated with unexposed females and males, to examine the effect of lead exposure on reproductive function. Male fertility was not affected but reduced female fertility was observed: litters were smaller and a smaller number of implantation sites was found in lead-exposed females. In lead-exposed males, the weights of the body, testes and epididymes diminished by about 13%, and seminal vesicle and ventral prostate weights, by about 29%. Testicular histology and the number and morphology of epididymal spermatozoa were normal. The levels of plasma FSH, LH and testosterone, and of testicular testosterone, were not modified. These results suggest that the hypothalamic-pituitary-testicular axis is not adversely affected by the above lead exposure, and that therefore the decreased seminal vesicle and ventral prostate weights might not be the consequence of reduced testosterone levels. The hypothesis that lead has a direct effect on these organs as well as a secondary effect resulting from possibly reduced food consumption by lead-exposed mice cannot be excluded. Consequently, in male NMRI mice, exposure to lead might affect reproductive function by acting directly and/or indirectly on accessory sex organs.

  3. Studies on the effects of lead toxicity on glutathione metabolism in the chick

    SciTech Connect

    McGowan, C.

    1985-01-01

    Studies were performed to investigate certain aspects of lead toxicity in the chick. In the first study, the mechanism of the Pb-induced changes in glutathione (GSH) metabolism was examined by comparing changes in organ non-protein thiol concentrations during the administration of Pb by intraperitoneal injection (acute) or in the diet (chronic). The synthesis of GSH in the liver was increased by both acute and chronic Pb administration when evaluated in terms of the rate of incorporation of (I/sup 14/C)-glycine into hepatic GSH. Total nonprotein sulfhydryl (NPSH) concentrations were also increased by both acute and chronic Pb. However, that portion of NPSH which is GSH was increased only by prolonged (chronic) exposure to Pb. The administration of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, decreased hepatic HPDH and GSH concentrations both in the presence and absence of injected Pb and inhibited the effects of dietary Pb on hepatic NPSH and GSH concentrations. The data suggested an immediate release of NPSH compounds into blood plasma following acute PB injection. Thus, the interorgan translocation system for GSH may be important in acute Pb intoxication in that it facilitates an immediate response to maintain cellular GSH levels being depleted by detoxification reactions by increasing the rate of GSH turnover. The antagonistic relationship between Pb and Se was investigated in terms of chick body weight gain and changes in organ non-protein thiol concentrated when administered with diets containing deficient adequate, and excess amounts of Se. Growth depression by 2000 ppm dietary Pb was observed with diets that were either deficient or adequate in dietary Se.

  4. Toxicity of nanosilver in intragastric studies: Biodistribution and metabolic effects.

    PubMed

    Hendrickson, Olga D; Klochkov, Sergey G; Novikova, Oksana V; Bravova, Irina M; Shevtsova, Elena F; Safenkova, Irina V; Zherdev, Anatoly V; Bachurin, Sergey O; Dzantiev, Boris B

    2016-01-22

    The unique physicochemical properties of silver nanoparticles explain their extensive application in consumer goods, food, and medicinal products. However, the biological effects of nanosilver after peroral exposure of mammals are still debatable. This study describes the biodistribution and biological action of 12nm non-coated silver nanoparticles intragastrically administered to male rats after acute (single exposure) and sub-acute (multiple exposures over 30 days) toxicity experiments. The daily doses were 2000 and 250mg/kg of body weight for single and multiple administrations, respectively. Silver tissue detection was conducted by elemental analysis with the help of atomic absorption spectroscopy. An estimation of the state of exposed animals was made and the dynamics of hematological and biochemical parameters of rats was studied. It was demonstrated that single and multiple administrations resulted in silver accumulation in the liver, kidneys, spleen, stomach, and small intestine. After both one- and repeated-dose exposures, the highest Ag contents were detected in the liver (0.87±0.37μg/g of organ) and kidneys (0.24±0.02μg/g of organ). The concentrations of silver detected in tissues were far smaller than the administered doses (<99%), indicating its efficient excretion from the organism. Acute and sub-acute exposures caused no animal mortality or signs of toxicity, manifested as changes in outward appearance or notable deviations in behavior or locomotor activity. Postmortem study revealed no visible pathomorphological abnormalities of internal organs. Hematological indices and biochemical parameters of the treated rats did not differ from those of the vehicle control animals. Overall, it can be concluded that nanosilver is able to be absorbed from the gastrointestinal tract into the bloodstream and accumulate in the secondary organs of rats. It showed no distinct toxicity under the experimental conditions of this study.

  5. Interacting effects of pH acclimation, and pH and heavy metals on acute and chronic toxicity to Ceriodaphnia dubia (Cladocera)

    SciTech Connect

    Belanger, S.E.; Cherry, D.S. )

    1990-05-01

    Understanding the factors that modify the sensitivity of the zooplankton Ceriodaphnia dubia to toxicants is important to the interpretation of chronic toxicity data generated for granting industrial permits. Early reports of high sensitivity of Ceriodaphnia to brief pH excursions led toxicologists to question the use of C. dubia as a test organism. Acute and chronic toxicity of pH and heavy metals, pH acclimation to acidic and alkaline conditions and the role of pH in modifying heavy metal (copper and zinc) toxicities were investigated. Ceriodaphnia dubia acclimated near neutral pH had acute (48-hr) lethal concentrations of 4.6 and 10.3 SU. Reproduction and mortality were not impaired between pH 6.14-8.99 regardless of pH acclimation history. Reproduction was significantly impaired beyond these extremes. Acute exposures to both heavy metals at pH 6, 8 and 9 and in water hardness of 180, 110 and 100 mg/L showed C dubia was consistently most sensitive in low pH and low hardness waters. Reproduction and mortality were not so affected by pH in chronic exposures. Similar concentrations of metals at all pH levels resulted in equivalent reductions in offspring per female. The results strongly suggest that effluent guidelines for pH at 6-9 are sound, and that toxicant activity in chronic time frames is directed primarily by concentration and water hardness, not by pH. 34 refs., 2 figs., 8 tabs.

  6. Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

    PubMed

    Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

    2015-07-01

    The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests.

  7. Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

    PubMed

    Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

    2015-07-01

    The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. PMID:25732700

  8. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  9. Oxidative stress, biochemical alterations, and hyperlipidemia in female rats induced by lead chronic toxicity during puberty and post puberty periods

    PubMed Central

    Alya, Annabi; Ines, Dhouib Bini; Montassar, Lasram; Najoua, Gharbi; Saloua, El Fazâa

    2015-01-01

    Objective(s): Lead (Pb) is a toxic metal inducing many destructive effects leading to a broad range of physiological, biochemical, and neurological dysfunctions in humans and laboratory animals. Materials and Methods: Here, we investigated the effect of chronic exposure to Pb (50 mg/l) on oxidative stress, hepatotoxicity, nephrotoxicity, and lipid profile of two different age groups of female rats treated with Pb from delivery until puberty period (40 days, Pb40) and post puberty period (65 days, Pb65). Results: Our results clearly show that the administration of Pb produces oxidative damage in liver and kidney, as strongly suggested by the significant increase in TBARS, decrease in total SH, and the alteration of SOD activity. Elevation in liver function biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduction in total protein (liver and plasma) and albumin are evidence of perturbations of liver synthetic function. In young Pb-treated group, Pb-induced nephropathy was more pronounced by the increase in the levels of creatinine, urea, and uric acid. However, hyperlipidemia was evident for both Pb-exposed groups leading to a potential risk for cardiovascular diseases and atherosclerosis. Conclusion: It is concluded that Pb induces metabolic and oxidative disturbances depending on the age of the animals, which are not negligible. PMID:26730340

  10. GENE INDUCTION STUDIES AND TOXICITY OF CHEMICAL MIXTURES

    EPA Science Inventory

    As part of its mixtures program the Agency for Toxic Substances and Disease Registry (ATSDR) supports in vitro and limited in vivo toxicity testing to further our understanding of the toxicity and health effects of chemical mixtures. There are increasing concerns that environment...

  11. Developmental toxicity studies of four fragrances in rats.

    PubMed

    Christian, M S; Parker, R M; Hoberman, A M; Diener, R M; Api, A M

    1999-12-20

    Four fragrances, 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-ben zopyran (HHCB), musk ketone and musk xylene were tested for developmental toxicity in Sprague-Dawley rats (25/group, 3 groups/fragrance, 2 fragrances/corn oil control). Dosages tested were HHCB: 50, 150, 500 mg/kg per day; AHTN: 5, 15, 50 mg/kg per day; musk ketone: 15, 45, 150 mg/kg per day; musk xylene: 20, 60, 200 mg/kg per day. All dosages tested exceeded multiples of the estimated maximal daily human dermal exposure. Treatment (gavage, 5 ml/kg) occurred on GDs 7-17 and Caesarean-sectioning on GD 20. Based on the results of these studies, none of the four fragrances tested were more toxic in the conceptuses than in the dams. Maternal NOAELs were 50, 5, 15 and 20 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively (150, 50, 45 and 60 mg/kg per day caused clinical signs and reduced weight gain and feed consumption). Developmental NOAELs were 150, 50, 45 and 200 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively. No adverse effects on embryo-fetal viability, growth or morphology occurred at the highest dosages of AHTN (50 mg/kg per day) or musk xylene (200 mg/kg per day). Developmental toxicity occurred at the high-dosages of HHCB (axial skeletal malformations at 500 mg/kg per day) and musk ketone (increased postimplantation loss and reduced fetal body weight at 150 mg/kg per day). The results of this study indicate that under conditions of normal use, the tested fragrances do not pose a risk to human conceptuses.

  12. A Study on Subchronic Inhalation Toxicity of 1-Chloropropane

    PubMed Central

    Chung, Yong Hyun; Han, Jeong Hee

    2015-01-01

    This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats. PMID:26877841

  13. Chronic Effects of Coated Silver Nanoparticles on Marine Invertebrate Larvae: A Proof of Concept Study

    PubMed Central

    Chan, Christine Ying Shan; Chiu, Jill Man Ying

    2015-01-01

    Silver nanoparticles (AgNPs), owing to their unique physical and chemical properties, have become increasingly popular in consumer products. However, data on their potential biological effects on marine organisms, especially invertebrates, remain very limited. This proof of principle study reports the chronic sub-lethal toxicity of two coated AgNPs (oleic acid coated AgNPs and polyvinylpyrrolidone coated AgNPs) on marine benthic invertebrate larvae across three phyla (i.e., the barnacle Balanus Amphitrite, the slipper-limpet Crepidula onyx, and the polychaete Hydroides elegans) in terms of growth, development, and metamorphosis. Bioaccumulation and biodistribution of silver were also investigated. Larvae were also exposed to silver nitrate (AgNO3) in parallel to distinguish the toxic effects derived from nano-silver and the aqueous form of silver. The sub-lethal effect of chronic exposure to coated AgNPs resulted in a significant retardation in growth and development, and reduction of larval settlement rate. The larval settlement rate of H. elegans was significantly lower in the coated AgNP treatment than the AgNO3 treatment, suggesting that the toxicity of coated AgNPs might not be solely evoked by the release of silver ions (Ag+) in the test medium. The three species accumulated silver effectively from coated AgNPs as well as AgNO3, and coated AgNPs were observed in the vacuoles of epithelial cell in the digestive tract of C. onyx. Types of surface coatings did not affect the sub-lethal toxicity of AgNPs. This study demonstrated that coated AgNPs exerted toxic effects in a species-specific manner, and their exposure might allow bioaccumulation of silver, and affect growth, development, and settlement of marine invertebrate larvae. This study also highlighted the possibility that coated AgNPs could be taken up through diet and the toxicity of coated AgNPs might be mediated through toxic Ag+ as well as the novel modalities of coated AgNPs. PMID:26171857

  14. Chronic Effects of Coated Silver Nanoparticles on Marine Invertebrate Larvae: A Proof of Concept Study.

    PubMed

    Chan, Christine Ying Shan; Chiu, Jill Man Ying

    2015-01-01

    Silver nanoparticles (AgNPs), owing to their unique physical and chemical properties, have become increasingly popular in consumer products. However, data on their potential biological effects on marine organisms, especially invertebrates, remain very limited. This proof of principle study reports the chronic sub-lethal toxicity of two coated AgNPs (oleic acid coated AgNPs and polyvinylpyrrolidone coated AgNPs) on marine benthic invertebrate larvae across three phyla (i.e., the barnacle Balanus Amphitrite, the slipper-limpet Crepidula onyx, and the polychaete Hydroides elegans) in terms of growth, development, and metamorphosis. Bioaccumulation and biodistribution of silver were also investigated. Larvae were also exposed to silver nitrate (AgNO3) in parallel to distinguish the toxic effects derived from nano-silver and the aqueous form of silver. The sub-lethal effect of chronic exposure to coated AgNPs resulted in a significant retardation in growth and development, and reduction of larval settlement rate. The larval settlement rate of H. elegans was significantly lower in the coated AgNP treatment than the AgNO3 treatment, suggesting that the toxicity of coated AgNPs might not be solely evoked by the release of silver ions (Ag+) in the test medium. The three species accumulated silver effectively from coated AgNPs as well as AgNO3, and coated AgNPs were observed in the vacuoles of epithelial cell in the digestive tract of C. onyx. Types of surface coatings did not affect the sub-lethal toxicity of AgNPs. This study demonstrated that coated AgNPs exerted toxic effects in a species-specific manner, and their exposure might allow bioaccumulation of silver, and affect growth, development, and settlement of marine invertebrate larvae. This study also highlighted the possibility that coated AgNPs could be taken up through diet and the toxicity of coated AgNPs might be mediated through toxic Ag+ as well as the novel modalities of coated AgNPs. PMID:26171857

  15. Chronic hepatitis: a retrospective study in 34 dogs.

    PubMed Central

    Fuentealba, C; Guest, S; Haywood, S; Horney, B

    1997-01-01

    The aims of this study were to characterize the histological changes observed in 34 accessioned cases of canine chronic hepatitis and to correlate these changes with the clinical pathological data. Cases of chronic hepatitis were subdivided into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis (5/34). Iron accumulation was a consistent finding in all livers examined. Although all cases of chronic hepatitis had elevated liver enzymes, no correlation was detected between biochemical parameters and the severity of morphologic changes. Similarly, no correlation was detected between rhodanine staining for copper and morphologic or biochemical indicators of cholestasis. However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic acini due to fibrosis could influence storage of copper. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. PMID:9187802

  16. Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.

    PubMed

    Rhee, Gyu Seek; Cho, Dae Hyun; Won, Yong Hyuck; Seok, Ji Hyun; Kim, Soon Sun; Kwack, Seung Jun; Lee, Rhee Da; Chae, Soo Yeong; Kim, Jae Woo; Lee, Byung Mu; Park, Kui Lea; Choi, Kwang Sik

    2005-12-10

    Each specific protein has an individual gene encoding it, and a foreign gene introduced to a plant can be used to synthesize a new protein. The identification of potential reproductive and developmental toxicity from novel proteins produced by genetically modified (GM) crops is a difficult task. A science-based risk assessment is needed in order to use GM crops as a conventional foodstuff. In this study, the specific characteristics of GM food and low-level chronic exposure were examined using a five-generation animal study. In each generation, rats were fed a solid pellet containing 5% GM potato and non-GM potato for 10 wk prior to mating in order to assess the potential reproductive and developmental toxic effects. In the multigeneration animal study, there were no GM potato-related changes in body weight, food consumption, reproductive performance, and organ weight. Polymerase chain reaction (PCR) was carried out using extracted genomic DNA to examine the possibility of gene persistence in the organ tissues after a long-term exposure to low levels of GM feed. In each generation, the gene responsible for bar was not found in any of the reproductive organs of the GM potato-treated male and female rats, and the litter-related indexes did not show any genetically modified organism (GMO)-related changes. The results suggest that genetically modified crops have no adverse effects on the multigeneration reproductive-developmental ability.

  17. Multigeneration reproductive and developmental toxicity study of bar gene inserted into genetically modified potato on rats.

    PubMed

    Rhee, Gyu Seek; Cho, Dae Hyun; Won, Yong Hyuck; Seok, Ji Hyun; Kim, Soon Sun; Kwack, Seung Jun; Lee, Rhee Da; Chae, Soo Yeong; Kim, Jae Woo; Lee, Byung Mu; Park, Kui Lea; Choi, Kwang Sik

    2005-12-10

    Each specific protein has an individual gene encoding it, and a foreign gene introduced to a plant can be used to synthesize a new protein. The identification of potential reproductive and developmental toxicity from novel proteins produced by genetically modified (GM) crops is a difficult task. A science-based risk assessment is needed in order to use GM crops as a conventional foodstuff. In this study, the specific characteristics of GM food and low-level chronic exposure were examined using a five-generation animal study. In each generation, rats were fed a solid pellet containing 5% GM potato and non-GM potato for 10 wk prior to mating in order to assess the potential reproductive and developmental toxic effects. In the multigeneration animal study, there were no GM potato-related changes in body weight, food consumption, reproductive performance, and organ weight. Polymerase chain reaction (PCR) was carried out using extracted genomic DNA to examine the possibility of gene persistence in the organ tissues after a long-term exposure to low levels of GM feed. In each generation, the gene responsible for bar was not found in any of the reproductive organs of the GM potato-treated male and female rats, and the litter-related indexes did not show any genetically modified organism (GMO)-related changes. The results suggest that genetically modified crops have no adverse effects on the multigeneration reproductive-developmental ability. PMID:16326439

  18. Studies of the toxic interaction of disinfection by-products

    SciTech Connect

    Laurie, R.D.; Bercz, J.P.; Wessendarp, T.K.; Condie, L.W.

    1986-11-01

    A large number and variety of compounds are formed in the process of chlorinating drinking water. Many of the compounds have been shown to be toxic and are currently being further evaluated by the US Environmental Protection Agency (EPA). One group of the halopropanones found in chlorinated drinking water is the dichloropropanones. The toxicological properties of this group have not been well characterized. In addition, a number of investigators have shown that ketones potentiate the hepatotoxicity of haloalkanes. The authors conducted a series of studies to explore both the toxicity of the dichloropropanones and their potential interaction with a well-characterized haloalkane, carbon tetrachloride. A variety of toxicological and biochemical endpoints were used to evaluate the toxicity of the dichloropropanones and their interaction with CCl/sub 4/, including cytochrome P-450 concentration, reduced glutathione levels, pentane generation, serum enzyme activities, and histopathology. Administration of 1,1-dichloropropanone (DCP) resulted in elevated serum enzymes associated with periportal necrosis. Glutathione levels were reduced by the administration of 1,1-DCP; pentane generation was not increased. When 1,1-DCP was given prior to CCl/sub 4/, the data were consistent with additivity. Administration of 1,3-DCP did not result in elevated serum enzymes, nor was there histopathologic evidence of necrosis. Glutathione levels and pentane generation in the 1,3-DCP-treated groups were the same as those of controls. Inhibition of the toxicologic effects of CCl/sub 4/ in a dose-related manner was observed when 1,3-DCP was administered prior to CCl/sub 4/.

  19. Fumonisin toxicity and metabolism studies at the USDA. Fumonisin toxicity and metabolism.

    PubMed

    Norred, W P; Voss, K A; Riley, R T; Plattner, R D

    1996-01-01

    Fumonisins are responsible for many of the toxic effects of the common corn fungus, Fusarium moniliforme. They are acute renal and liver toxins in rats, and have tumor promoting activity. Fumonisin B1 is poorly absorbed, rapidly excreted, and persists in small amounts in the liver and kidney. Fumonisins are specific inhibitors of ceramide synthase, and the toxic effects they produce may be related to their ability to disrupt sphingolipid metabolism, resulting in a myriad of problems in cell regulation and communication. In this paper, research that has been conducted on F. monilforme and the fumonisins at the USDA's Russell Research Center is reviewed.

  20. Preliminary results of a phase I/II study of sodium pentosanpolysulfate in the treatment of chronic radiation-induced proctitis

    SciTech Connect

    Grigsby, P.W.; Pilepich, M.V.; Parsons, C.L. )

    1990-02-01

    This is a report of a phase I/II study of 13 patients treated with sodium pentosanpolysulfate (PPS) for chronic radiation-induced proctitis. A complete response was obtained in 82%, a partial response occurred in 9%, and 9% failed to respond to therapy. No significant toxicity was observed. It is concluded that PPS is an effective treatment for chronic radiation-induced proctitis and a phase III randomized, double-blind study of PPS versus placebo is planned.

  1. Understanding the chronic impacts of oil refinery wastewater requires consideration of sediment contributions to toxicity.

    PubMed

    Loughery, Jennifer R; Arciszewski, Tim J; Kidd, Karen A; Mercer, Angella; Hewitt, L Mark; Maclatchy, Deborah L; Munkittrick, Kelly R

    2014-01-01

    Previous studies at an oil refinery in Saint John, New Brunswick, Canada, found a diminished fish community downstream of the effluent outfall that appeared to be associated with periodic low dissolved oxygen concentrations due to episodic discharges of contaminated transport vessel ballast water. This study was initiated after the ballast water was removed from the effluent to further investigate the potential causes of residual effects in the study stream, Little River. We used field caging of fish, laboratory bioassays, and chemical analysis of effluents and sediments from the field site to determine if the effluent or contaminated sediments were affecting the recovery of the fish community in Little River. The field studies suggested that exposed, caged fish were affected, displaying >40 % increases in liver sizes and increased liver detoxification enzyme activity (cytochrome P450 1A, CYP1A); however, similar responses were absent in laboratory exposures that used effluent only. Adding sediments collected from the vicinity of the refinery's outfall to the laboratory bioassays reproduced some of the field responses. Chemical analyses showed high concentrations of PAHs in sediments but low concentrations in the effluent, suggesting that the PAHs in the sediment were contributing more to the impacts than the effluent. Application of effects-based monitoring is suggested as beneficial to identify impacts to fisheries where refinery effluents of this type are involved.

  2. Improving sediment-quality guidelines for nickel: development and application of predictive bioavailability models to assess chronic toxicity of nickel in freshwater sediments.

    PubMed

    Vangheluwe, Marnix L U; Verdonck, Frederik A M; Besser, John M; Brumbaugh, William G; Ingersoll, Christopher G; Schlekat, Christan E; Garman, Emily Rogevich

    2013-11-01

    Within the framework of European Union chemical legislations an extensive data set on the chronic toxicity of sediment nickel has been generated. In the initial phase of testing, tests were conducted with 8 taxa of benthic invertebrates in 2 nickel-spiked sediments, including 1 reasonable worst-case sediment with low concentrations of acid-volatile sulfide (AVS) and total organic carbon. The following species were tested: amphipods (Hyalella azteca, Gammarus pseudolimnaeus), mayflies (Hexagenia sp.), oligochaetes (Tubifex tubifex, Lumbriculus variegatus), mussels (Lampsilis siliquoidea), and midges (Chironomus dilutus, Chironomus riparius). In the second phase, tests were conducted with the most sensitive species in 6 additional spiked sediments, thus generating chronic toxicity data for a total of 8 nickel-spiked sediments. A species sensitivity distribution was elaborated based on 10% effective concentrations yielding a threshold value of 94 mg Ni/kg dry weight under reasonable worst-case conditions. Data from all sediments were used to model predictive bioavailability relationships between chronic toxicity thresholds (20% effective concentrations) and AVS and Fe, and these models were used to derive site-specific sediment-quality criteria. Normalization of toxicity values reduced the intersediment variability in toxicity values significantly for the amphipod species Hyalella azteca and G. pseudolimnaeus, but these relationships were less clearly defined for the mayfly Hexagenia sp. Application of the models to prevailing local conditions resulted in threshold values ranging from 126 mg to 281 mg Ni/kg dry weight, based on the AVS model, and 143 mg to 265 mg Ni/kg dry weight, based on the Fe model. PMID:23983116

  3. Improving sediment-quality guidelines for nickel: development and application of predictive bioavailability models to assess chronic toxicity of nickel in freshwater sediments

    USGS Publications Warehouse

    Vangheluwe, Marnix L. U.; Verdonck, Frederik A. M.; Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.; Schlekat, Christan E.; Rogevich Garman, Emily

    2013-01-01

    Within the framework of European Union chemical legislations an extensive data set on the chronic toxicity of sediment nickel has been generated. In the initial phase of testing, tests were conducted with 8 taxa of benthic invertebrates in 2 nickel-spiked sediments, including 1 reasonable worst-case sediment with low concentrations of acid-volatile sulfide (AVS) and total organic carbon. The following species were tested: amphipods (Hyalella azteca, Gammarus pseudolimnaeus), mayflies (Hexagenia sp.), oligochaetes (Tubifex tubifex, Lumbriculus variegatus), mussels (Lampsilis siliquoidea), and midges (Chironomus dilutus, Chironomus riparius). In the second phase, tests were conducted with the most sensitive species in 6 additional spiked sediments, thus generating chronic toxicity data for a total of 8 nickel-spiked sediments. A species sensitivity distribution was elaborated based on 10% effective concentrations yielding a threshold value of 94 mg Ni/kg dry weight under reasonable worst-case conditions. Data from all sediments were used to model predictive bioavailability relationships between chronic toxicity thresholds (20% effective concentrations) and AVS and Fe, and these models were used to derive site-specific sediment-quality criteria. Normalization of toxicity values reduced the intersediment variability in toxicity values significantly for the amphipod species Hyalella azteca and G. pseudolimnaeus, but these relationships were less clearly defined for the mayfly Hexagenia sp. Application of the models to prevailing local conditions resulted in threshold values ranging from 126 mg to 281 mg Ni/kg dry weight, based on the AVS model, and 143 mg to 265 mg Ni/kg dry weight, based on the Fe model

  4. Improving sediment-quality guidelines for nickel: development and application of predictive bioavailability models to assess chronic toxicity of nickel in freshwater sediments.

    PubMed

    Vangheluwe, Marnix L U; Verdonck, Frederik A M; Besser, John M; Brumbaugh, William G; Ingersoll, Christopher G; Schlekat, Christan E; Garman, Emily Rogevich

    2013-11-01

    Within the framework of European Union chemical legislations an extensive data set on the chronic toxicity of sediment nickel has been generated. In the initial phase of testing, tests were conducted with 8 taxa of benthic invertebrates in 2 nickel-spiked sediments, including 1 reasonable worst-case sediment with low concentrations of acid-volatile sulfide (AVS) and total organic carbon. The following species were tested: amphipods (Hyalella azteca, Gammarus pseudolimnaeus), mayflies (Hexagenia sp.), oligochaetes (Tubifex tubifex, Lumbriculus variegatus), mussels (Lampsilis siliquoidea), and midges (Chironomus dilutus, Chironomus riparius). In the second phase, tests were conducted with the most sensitive species in 6 additional spiked sediments, thus generating chronic toxicity data for a total of 8 nickel-spiked sediments. A species sensitivity distribution was elaborated based on 10% effective concentrations yielding a threshold value of 94 mg Ni/kg dry weight under reasonable worst-case conditions. Data from all sediments were used to model predictive bioavailability relationships between chronic toxicity thresholds (20% effective concentrations) and AVS and Fe, and these models were used to derive site-specific sediment-quality criteria. Normalization of toxicity values reduced the intersediment variability in toxicity values significantly for the amphipod species Hyalella azteca and G. pseudolimnaeus, but these relationships were less clearly defined for the mayfly Hexagenia sp. Application of the models to prevailing local conditions resulted in threshold values ranging from 126 mg to 281 mg Ni/kg dry weight, based on the AVS model, and 143 mg to 265 mg Ni/kg dry weight, based on the Fe model.

  5. Assessment of chronic toxicity of petroleum and produced water components to marine organisms. Final technical summary

    SciTech Connect

    Cherr, G.N.; Higashi, R.M.; Shenker, J.M.

    1993-05-31

    The objectives of the report were: (1) to determine the effects of produced water exposure in early life stages of marine plants and animals, at the cellular, subcellular, and physiological levels; (2) to determine the effects of produced water exposure on reproduction in marine organisms; and (3) to develop non-invasive approaches for assessing reproductive impairment. The effects of produced water (PW) was assessed on development in three ecologically and economically important species, the purple sea urchin (Strongylocentrotus purpuratus), the giant kelp (macrocystis pyrifera), and tsahe California mussel (Mytilus califonrnianus). To determine the basis for effects of PW on these developing organisms, some fundamental studies were prerequisite. Furthermore, eggs and embryos from adults which were outplanted near the discharge were also studied. Finally, the biochemical response of embryos to PW was also defined.

  6. Comparative study on the toxicity of pyrethroids, α-cypermethrin and deltamethrin to Ceriodaphnia dubia.

    PubMed

    Shen, Mei-Fang; Kumar, Anupama; Ding, Shu-Yan; Grocke, Sonia

    2012-04-01

    Two synthetic pyrethroid pesticides, α-cypermethrin and deltamethrin were investigated as potential toxic contaminants. The acute and chronic bioassays were conducted using Ceriodaphnia dubia. The toxicity of α-cypermethrin and deltamethrin to C. dubia increased with increasing concentrations and exposure time. C. dubia was three times more sensitive to deltamethrin than to α-cypermethrin with 48-h EC(50) of 0.06 μg/L and 0.23 μg/L, respectively. The chronic EC(50) values for α-cypermethrin and deltamethrin were 97.8 and 34.7 ng/L, respectively. Eight-day growth of Ceriodaphnia neonates during chronic exposures was the most sensitive endpoint measured in comparison to the endpoints of survival and number of neonates produced. To gain a better understanding of the link between acute and chronic toxicity, the acute-to chronic ratios (ACRs) were also calculated for survival, growth and reproduction endpoints. ACRs varied between 11 and 224 for the two pyrethroids. These results suggest that at environmentally relevant low concentrations, α-cypermethrin and deltamethrin could have significant adverse effects on the survival, reproduction and growth of C. dubia.

  7. Ex-vivo assessment of chronic toxicity of low levels of cadmium on testicular meiotic cells

    SciTech Connect

    Geoffroy-Siraudin, Cendrine; Perrard, Marie-Hélène; Ghalamoun-Slaimi, Rahma; Ali, Sazan; Chaspoul, Florence; Lanteaume, André; Achard, Vincent; Gallice, Philippe; Durand, Philippe; and others

    2012-08-01

    Using a validated model of culture of rat seminiferous tubules, we assessed the effects of 0.1, 1 and 10 μg/L cadmium (Cd) on spermatogenic cells over a 2‐week culture period. With concentrations of 1 and 10 μg/L in the culture medium, the Cd concentration in the cells, determined by ICP-MS, increased with concentration in the medium and the day of culture. Flow cytometric analysis enabled us to evaluate changes in the number of Sertoli cells and germ cells during the culture period. The number of Sertoli cells did not appear to be affected by Cd. By contrast, spermatogonia and meiotic cells were decreased by 1 and 10 μg/L Cd in a time and dose dependent manner. Stage distribution of the meiotic prophase I and qualitative study of the synaptonemal complexes (SC) at the pachytene stage were performed by immunocytochemistry with an anti SCP3 antibody. Cd caused a time-and-dose-dependent increase of total abnormalities, of fragmented SC and of asynapsis from concentration of 0.1 μg/L. Additionally, we observed a new SC abnormality, the “motheaten” SC. This abnormality is frequently associated with asynapsis and SC widening which increased with both the Cd concentration and the duration of exposure. This abnormality suggests that Cd disrupts the structure and function of proteins involved in pairing and/or meiotic recombination. These results show that Cd induces dose-and-time-dependent alterations of the meiotic process of spermatogenesis ex-vivo, and that the lowest metal concentration, which induces an adverse effect, may vary with the cell parameter studied. -- Highlights: ► Cadmium induces ex-vivo severe time- and dose-dependent germ cell abnormalities. ► Cadmium at very low concentration (0.1 µg/l) induces synaptonemal complex abnormalities. ► The lowest concentration inducing adverse effect varied with the cell parameter studied. ► Cadmium alters proteins involved in pairing and recombination. ► Cadmium leads to achiasmate univalents and

  8. Epidemiological investigation on chronic copper toxicity to children exposed via the public drinking water supply.

    PubMed

    Zietz, Björn P; Dieter, Hermann H; Lakomek, Max; Schneider, Heide; Kessler-Gaedtke, Barabara; Dunkelberg, Hartmut

    2003-01-20

    Copper in drinking water has been associated with Non-Indian Childhood Cirrhosis (NICC), a form of early childhood liver cirrhosis. This epidemiological study examines the exposition of infants to increased copper concentrations through drinking water from public water supplies in Berlin, Germany, and if this dietary copper intake can cause liver damage in early childhood. In total, water samples from 2944 households with infants were tested for copper. Mean copper concentrations in the two different types of collected composite samples were 0.44 and 0.56 mg/l, respectively. Families having a copper concentration at or above 0.8 mg/l in one or both of the composite samples (29.9% of all sampled households) and a defined minimum ingestion of tap water of their infant were recommended to undergo a paediatric examination. Nearly every of the 541 recommended infants were examined by a local paediatrician and of these 183 received a blood serum analysis, too. None of the infants had clear signs of a liver disease although a few serum parameters lay outside the accompanying reference range and abdominal ultrasound imaging gave slightly unusual results in five cases. Additionally, no signs of a negative health effect could be found in the statistical analysis of the serum parameters GOT, GPT, GGT, total bilirubin, serum copper, or ceruloplasmin in relation to estimated daily and total copper intakes of the infants from tap water. No dose relation of serum parameters and estimated copper intakes could be established. From the results of the study, no confirmed indication of a liver malfunction in infants whose food had been prepared using tap water with an elevated copper concentration could be found and, therefore, no indication of a hazard due to copper pipes connected to public water supplies could be detected. PMID:12526904

  9. Possible Biomarkers of Chronic Stress Induced Exhaustion - A Longitudinal Study

    PubMed Central

    Wallensten, Johanna; Åsberg, Marie; Nygren, Åke; Szulkin, Robert; Wallén, Håkan; Mobarrez, Fariborz; Nager, Anna

    2016-01-01

    Background Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years. Methods and Findings Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0), after 12 months (T12) and after 24 months (T24). Blood samples were collected at inclusion (T0) in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up. Conclusions The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion. PMID:27145079

  10. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  11. Chronic toxicity of Clark Fork River invertebrates to rainbow trout when administered via the diet

    SciTech Connect

    Barth, A.; Cohen, A.; Stubblefield, W.

    1995-12-31

    A 46-day exposure examined the effects of metals contamination in a live natural freshwater diet on rainbow trout fry. Survival, growth, and whole-body tissue metals were compared among groups of trout fed live planktonic invertebrates (primarily Daphnia pulex) collected from the Clark Fork River (CFR), Montana and trout fed live laboratory-reared D. pulex. Metals of interest in the diets were As, Cu, Cd, Pb, and Zn. In addition to dietary exposure, treatments included simultaneous exposure to a mixture of waterborne metals (Cu, Cd, Pb, and Zn) at sublethal concentrations. Trout showed no statistically significant effects on survival or growth from mean CFR invertebrate metal concentrations of 20.1 mg As/kg dwt, 60.7 mg Cu/kg dwt, 4.0 mg Cd/kg dwt, 4.9 mg Pb/kg dwt, and 249 mg Zn/kg dwt. Waterborne and dietary Cd and Pb appeared to result in increased tissue concentrations of these metals, while only dietary As resulted in increased tissue As. Neither dietary nor waterborne copper or zinc had a substantial effect on tissue levels of these metals. Results were consistent, in terms of the lack of statistically significant growth and survival effects, with those of previous in-house studies exposing rainbow trout to metals-enriched Artemia sp. (brine shrimp) diets.

  12. Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study

    PubMed Central

    Jain, Preetesh; Kantarjian, Hagop; Jabbour, Elias; Gonzalez, Graciela Nogueras; Borthakur, Gautam; Pemmaraju, Naveen; Daver, Naval; Gachimova, Evguenia; Ferrajoli, Alessandra; Kornblau, Steven; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge

    2015-01-01

    Summary Background Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. Methods We did a single-arm, phase 2 trial at MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24, 2013, we enrolled patients with early (<6 months) chronic-phase CML and treated them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were given a starting dose of 45 mg per day; we lowered this due to tolerability issues and patients enrolled after this date were given a starting dose of 30 mg per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6, 2013, for vascular complications with ponatinib, we started all patients on aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day for all patients. The primary endpoint was the proportion of patients who achieved complete cytogenetic response by 6 months in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01570868. Findings We enrolled 51 patients. Median follow-up was 20.9 months (IQR 14.9–25.2). 43 patients were started on 45 mg ponatinib every day; eight patients were started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete cytogenetic response at 6 months. Most frequent toxicities included skin-related effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events (mainly hypertension) occurred in 25 (49%) patients. Grade 3–4 myelosuppression occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014, at the recommendation of the FDA due to concern about the increased risk of thromboembolism

  13. Pulmonary Toxicity Study of Lunar and Martian Dust Simulants Intratracheally Instilled in Mice

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; Latch, John A.; Holian, A.; McCluskey, R.

    2000-01-01

    NASA is contemplating sending humans to Mars and the Moon for further exploration. The properties of Hawaiian and Californian volcanic ashes allow them to be used to simulate Martian and lunar dusts, respectively. NASA laboratories use these dust simulants to test performance of hardware destined for Martian or lunar environments. Workers in these test facilities are exposed to low levels of these dusts. The present study was conducted to investigate the toxicity of these dust simulants. Particles of respirable-size ranges of lunar simulant (LS), Martian simulant (MS), TiO2 (negative control) and quartz (positive control) were each intratracheally instilled (saline as vehicle) to groups of 4 mice (C57BL, male, 2-3 month old) at a single treatment of 1 (Hi dose) or 0.1 (Lo dose) mg/mouse. The lungs were harvested at the end of 7 days or 90 days for histopathological examination. Lungs of the LS-Lo groups had no evidence of inflammation, edema or fibrosis. The LS-Hi-7d group had mild to moderate acute inflammation, and neutrophilic and lymphocytic infiltration; the LS-Hi-90d group showed signs of chronic inflammation and some fibrosis. Lungs of the MS-Lo-7d group revealed mild inflammation and neutrophilic and lymphocytic infiltration; the MS-Lo-90d group showed mild fibrosis and particle-laden macrophages (PLM). Lungs of the MS-Hi-7d group demonstrated mild to moderate inflammation and large foci of PLM; the MS-Hi-90d group showed chronic mild to moderate inflammation and fibrosis. To mimic the effects of the oxidative and reactive properties of Martian soil surface, groups of mice were exposed to ozone (3 hour at 0.5 ppm) prior to MS dust instillation. Lung lesions in the MS group were more severe with the pretreatment. The results for the negative and positive controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic insults to the lungs were TiO2study, blood samples were

  14. Acute and chronic toxicity testing of TPH-contaminated soils with the earthworm, Eisenia foetida

    SciTech Connect

    Stewart, A.J.; Wicker, L.F.; Nazerias, M.S.

    1995-12-31

    Responses of Eisenia foetida to petroleum-contaminated soils are being assessed using a 21-day test described previously. The authors prepared dilutions of two soils, referred to as A and B, using their reference-soil counterparts, collected from near the contaminated sites. The total petroleum hydrocarbon (TPH) content of each soil was measured by latroscan before the dilutions were prepared. References for the A and B soils contained 167 and 1,869 ppm of TPH, respectively. Thus, neither reference soil was pristine. Dilutions of the A soil tested with E. foetida contained from 179 to 305 ppm TPH; dilutions of the B soil contained from 1,875 to 1,950 ppm TPH. E foetida survival was 100% in both dilution series. Mean growth of Eisenia in dilutions of the A soil ranged from 48 to 74 mg dry-weight growth per pair of worms; these values were lower than those in any dilution of the B soil series. Lipid levels of worms in higher concentrations of the A and B soils were similar to one another and to published values, suggesting little inhibition of feeding in either dilution series. Earthworm reproduction was zero in the A series, but moderately high in the B series. Thus, the A soil apparently contained materials other than TPH that inhibited earthworm growth and reproduction. This study shows that (1) TPH at concentrations as high as 1,800 ppm may not always be inhibitor to earthworm growth or reproduction and (2) that earthworm survival, as a test endpoint, is much less sensitive than either growth or reproduction.

  15. Recent studies on biomethylation and demethylation of toxic elements.

    PubMed

    Ridley, W P; Dizikes, L; Cheh, A; Wood, J M

    1977-08-01

    Methylcobalamin (methyl-B12) has been implicated in the biomethylation of the heavy metals (mercury, tin, platinum, gold, and thallium) as well as the metalloids (arsenic, selenium, tellurium and sulfur). In addition, methylcobalamin has been shown to react with lead, but the lead-alkyl product is unstable in water. Details of the kinetics and mechanisms for biomethylation of arsenic are presented, with special emphasis on synergistic reactions between metal and metalloids in different oxidation states. This study explains why synergistic, or antagonistic, processes can occur when one toxic element reacts in the presence of another. The relative importance of biomethylation reactions involving methylcobalamin will be compared to those reactions where S-adenosylmethionine is involved.

  16. Historical control data in reproductive and developmental toxicity studies.

    PubMed

    Mylchreest, Eve; Harris, Stephen B

    2013-01-01

    Reproductive and developmental toxicity studies in laboratory animals are conducted as part of the process of evaluating the risk of pharmaceuticals and chemicals to human reproduction and development. In these studies, comparison of data from groups dosed with the test article to a concurrent control group is considered the most relevant approach for the interpretation of adverse effects. However, differences between the concurrent control and treated groups may arise by chance alone, and in some instances may even appear to be dose-related. These limitations of the concurrent control group are of particular concern when interpreting fetal malformation data because malformations are rare events that can be better characterized when incidences in both concurrent control and treated groups are compared to a larger set of control values. Historical control data can be useful not only to understand the range of normal for a given endpoint but also to monitor the biological variability over time due to various external factors (e.g., genetic changes in a strain, changes at the breeding facility). It can also serve to track the performance of the laboratory and identify any changes in the data that may be the result of internal factors at the performing laboratory due to modification in animal diet, seasonal changes, or even the proficiency of the technicians in handling animals and recording fetal and offspring observations. This chapter will provide the reader with guidance on building a laboratory historical control database and applying it to the scientific interpretation of reproductive and developmental toxicity data. Information on sources of external historical control data will be provided and some perspective given on the utility of this data. A discussion of the presentation of historical control data with descriptive statistics will be accompanied by examples of tabulation of the data. Supernumerary rib will be used as an example of how historical control

  17. Historical control data in reproductive and developmental toxicity studies.

    PubMed

    Mylchreest, Eve; Harris, Stephen B

    2013-01-01

    Reproductive and developmental toxicity studies in laboratory animals are conducted as part of the process of evaluating the risk of pharmaceuticals and chemicals to human reproduction and development. In these studies, comparison of data from groups dosed with the test article to a concurrent control group is considered the most relevant approach for the interpretation of adverse effects. However, differences between the concurrent control and treated groups may arise by chance alone, and in some instances may even appear to be dose-related. These limitations of the concurrent control group are of particular concern when interpreting fetal malformation data because malformations are rare events that can be better characterized when incidences in both concurrent control and treated groups are compared to a larger set of control values. Historical control data can be useful not only to understand the range of normal for a given endpoint but also to monitor the biological variability over time due to various external factors (e.g., genetic changes in a strain, changes at the breeding facility). It can also serve to track the performance of the laboratory and identify any changes in the data that may be the result of internal factors at the performing laboratory due to modification in animal diet, seasonal changes, or even the proficiency of the technicians in handling animals and recording fetal and offspring observations. This chapter will provide the reader with guidance on building a laboratory historical control database and applying it to the scientific interpretation of reproductive and developmental toxicity data. Information on sources of external historical control data will be provided and some perspective given on the utility of this data. A discussion of the presentation of historical control data with descriptive statistics will be accompanied by examples of tabulation of the data. Supernumerary rib will be used as an example of how historical control

  18. A Study on the D. magna and V. fischeri Toxicity Relationship of Industrial Wastewater from Korea

    NASA Astrophysics Data System (ADS)

    Pyo, S.; Lee, S.; Chun Sang, H.; Park, T. J.; Kim, M. S.

    2015-12-01

    It is well known that high concentration of TDS (total dissolved solid) in industrial effluent gives rise to the toxicity to the Daphnia magna toxicity test. D. magna is vulnerable to relatively low TDS concentration showing the 24-hr EC50 of Salinity 0.6% (as the sea salt concentration). Recently, standard mandatory toxicity testing using Daphnia magna has been used to monitor industrial effluent toxicity according to Korea standard method (Acute Toxicity Test Method of the Daphnia magna Straus (Cladocera, Crustacea), ES 04704. 1a) under regulation. Since only one acute toxicity testing is applied in the present, we are trying to introduce microbial battery for more complete toxicity assessment. In this study, the acute toxicities between daphnids and microbes were compared. The results of D. magna and Vibrio fischeri toxicity test from 165 industrial wastewater effluents showed high positive correlation. In addition, the possibility of predicting daphnia toxicity from the bacterial toxicity data amounts to 92.6% if we consider salinity effect (>5ppt) together. From this study, we found that the V. fischeri toxicity test is a powerful battery tool to assess the industrial wastewater toxicity. Here, we suggest that luminescent bacteria toxicity test be useful not only for complete toxicity assessment which can't be obtained by daphnia toxicity testing only but also for the reduction cost, time, and labor in the Korean society. Keywords : D. magna, V. fischeri, Industrial waste water, battery test Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

  19. Brain atrophy in chronic alcoholic patients: a quantitative pathological study.

    PubMed Central

    Harper, C; Kril, J

    1985-01-01

    There are essentially no objective neuropathological data on brain atrophy in chronic alcoholic patients despite numerous neuroradiological studies which show a high incidence of shrinkage or atrophy. Therefore measurements were made of the intracranial volume (ICV) and brain volume (BV) in a necropsy study of 25 chronic alcoholic patients and 44 controls. The pericerebral space (PICS) was calculated according to the formula (formula; see text) The PICS will increase in patients with brain atrophy since the ICV remains constant throughout life. The mean PICS value was 8.3% in controls, 11.3% in the alcoholic group, 14.7% in alcoholics with superimposed Wernicke's encephalopathy (thiamine deficiency) and 16.2% in those alcoholics with associated liver disease. Thus there was a statistically significant loss of brain tissue in chronic alcoholic patients which appeared to be more severe in those with associated nutritional vitamin deficiencies or alcoholic liver disease. Images PMID:3981189

  20. UVB dose-toxicity thresholds and steady-state DNA-photoproduct levels during chronic irradiation of inbred Xenopus laevis tadpoles.

    PubMed

    Pandelova, Iovanna; Hewitt, Stephen R; Rollins-Smith, Louise A; Hays, John B

    2006-01-01

    Environmental stressors that severely impact some species more than others can alter ecosystems and threaten biodiversity. Genotoxic stress, such as solar UV-B irradiance, may induce levels of DNA damage at rates that exceed repair capacities in some species but remain below repair capacities in other species. Repair rates would seem to establish toxicity thresholds. We used inbred Xenopus laevis tadpoles in the laboratory to test the hypothesis that balances between rates of induction of cyclobutane pyrimidine dimers (CPDs; the major UV-B photoproduct in DNA) and rates of CPD removal (repair) can determine UV-B toxicity thresholds. As rates of chronic UV-B irradiance were progressively increased by decreased shielding of lamps, survival decreased sharply over a relatively narrow range of dose rates. Apparent toxicity thresholds were associated with large increases in steady-state CPD levels. Induction at twice the measured removal (repair) rate produced sustained high CPDs and 100% mortality. Induction at one-half the removal rate resulted in negligible CPD levels and low mortality. Increased intensity of visible radiation available to drive CPD photoreactivation, mimicking interspecies variation in DNA repair capacity, reduced steady-state CPD levels and increased survival at UV-B dose rates that were previously toxic, resulting in increased thresholds of apparent toxicity. We suggest that threshold effects due to DNA repair should generally be considered in assessments of effects of genotoxic agents on species-specific population decreases and human health risks. PMID:17205633

  1. Study on Assessment of Renal Function in Chronic Liver Disease

    PubMed Central

    Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy

    2015-01-01

    Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647

  2. Organ-specific manganese toxicity: a comparative in vitro study on five cellular models exposed to MnCl(2).

    PubMed

    Rovetta, F; Catalani, S; Steimberg, N; Boniotti, J; Gilberti, M E; Mariggiò, M A; Mazzoleni, G

    2007-03-01

    Manganese (Mn) is both an essential nutrient and a toxicant, with specific effects on liver and kidney (acute exposure) and on central nervous system (CNS) (chronic exposure). Mn neurotoxicity includes neurobehavioral disorders and extra-pyramidal motor dysfunctions (manganism), possibly due to focal injuries to the basal ganglia. Even if widely investigated, the molecular mechanisms responsible for Mn toxicity remain to be clarified. Aim of this study was to identify suitable in vitro models to investigate these molecular pathways. To this purpose we compared the effect of manganese chloride on four cell lines, representative of the main target organs of Mn toxicity in vivo. HepG2 and MDCK cell lines were selected for liver and kidney, respectively; glial GL15 and neuronal SHSY5Y cells were used as models of CNS components. To complete the "motor system" model, skeletal muscle C2C12 cells were also included. Our results demonstrate that hepatic, renal, glial and neuronal cell types differently react to Mn, mirroring the specific in vivo response of the tissue they represent. This confirms their value as suitable in vitro models to study Mn-related toxic events. Interestingly, also muscle C2C12 cells showed a noticeable sensitivity to Mn, preferential targets being differentiated myotubes.

  3. MUSCLE TENDERNESS IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: THE CHRONIC PROSTATITIS COHORT STUDY

    PubMed Central

    Shoskes, Daniel A.; Berger, Richard; Elmi, Angelo; Landis, J. Richard; Propert, Kathleen J.; Zeitlin, Scott

    2009-01-01

    Introduction Myofascial pain is a possible etiology for category III chronic prostatitis/chronic pelvic pain syndrome (CPPS), either secondary to infection/inflammation or as the primary cause. We wished to document tenderness on physical exam in a large multicenter cohort of CPPS patients, and compare to controls. Methods Data were reviewed from the NIH Chronic Prostatitis Cohort study on 384 men with CPPS and 121 asymptomatic controls who had complete unblinded physical exam data, from 7 clinical centers between 10/98 - 8/01. Tenderness in 11 sites including prostate, genitals, abdomen and pelvic floor together with prostate size and consistency was evaluated. Data was correlated with cultures and symptoms. Results Overall, 51% of CPPS patients and 7% of controls had any tenderness. The most common site was prostate (41% CPPS, 5% controls), followed by external and internal pelvic floor (13% and 14% CPPS, 0 controls) and suprapubic (9% CPPS, 0 controls). In CPPS patients, 25% had 1 tender site, 11% had 2 and 6% had 3. Tenderness did not correlate with inflammation or infection in the prostate fluid. Prostate consistency was normal in 79% of CPPS patients and in 95% of controls, and did not correlate with symptom severity. CPPS patients with any tenderness had significantly higher CPSI scores at baseline, and at 1 year (24.1 vs 21.2 and 20.2 vs 17.5, p<0.0001), compared to patients without tenderness. Conclusions Abdominal/pelvic tenderness is present in half of CPPS patients, but only 7% of controls. Extraprostatic tenderness may identify a cohort of patients with a neuromuscular source of pain. PMID:18082223

  4. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology.

    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

    To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse outcomes relevant for risk assessment. In this paper, we focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritize higher tier toxicity testing. We argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. We further discuss information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species. We provide recommendations for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modeling approaches and with evolutionary life history theory. The extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models

  5. A brief study of toxic effects of some medicinal herbs on kidney

    PubMed Central

    Asif, Mohammad

    2012-01-01

    Increased use of complementary and alternative herbal medicines in the treatment of various diseases.Some herbal therapies may be causes of potential toxicity that may be renal toxicity caused by the ingestion of herbs. The goal of this study is the toxic and beneficial effects of medicinal herbs on renal health by which evidence for benefit or toxicity has been found. Included are nephrotoxicity from aristolochic acid and other components within herbs, herb-drug interactions, heavy metal toxicity in herbs and adulterants during careless preparation of herbal medicine, resulting in adverse renal effects and renal toxicity from contaminants within the extracts. The review aims to provide knowledge and guide to encourage future toxicity studies on the kidney by medicinal herbs. PMID:23326775

  6. Brain shrinkage in chronic alcoholics: a pathological study.

    PubMed Central

    Harper, C G; Kril, J J; Holloway, R L

    1985-01-01

    A quantitative neuropathological necropsy study of 22 control and 22 chronic alcoholic subjects showed a statistically significant loss of brain tissue in the chronic alcoholic group. The loss of tissue appeared to be from the white matter of the cerebral hemispheres rather than the cerebral cortex. This may reflect a primary alteration in the composition or structure of the white matter or it may be secondary to loss of nerve cells from the cortex with subsequent degeneration of the axons in the white matter. Further morphometric analyses including cortical neuronal counts will be necessary to clarify this issue. PMID:3918649

  7. Chronic liver disease in Kuala Lumpur, Malaysia: a clinical study.

    PubMed

    Kudva, M V; Zawawi, M M

    1990-08-01

    This study was undertaken to analyse the clinical spectrum of chronic liver disease (cirrhosis, and others with portal hypertension) in Kuala Lumpur. Eighty patients were diagnosed over a 6-year period. Twenty-two had biopsy proven cirrhosis while 58 others had portal hypertension with clinical and biochemical evidence of chronic liver disease. The commonest aetiology was alcohol (36%), followed by the idiopathic variety and hepatitis B. The male to female ratio was 4.4:1. Indians had a high prevalence of alcohol-associated chronic liver disease. Overall, ascites was the commonest presentation. Eight patients presented with hepatocellular carcinoma. Spontaneous bacterial peritonitis was diagnosed in 13% of patients undergoing abdominal paracentesis. Gallstones were detected in 37% of patients who underwent ultrasonography. Diabetes mellitus and peptic ulcer disease were noted in 22% and 31% of patients respectively.

  8. Doppler ultrasound study and venous mapping in chronic venous insufficiency.

    PubMed

    García Carriazo, M; Gómez de las Heras, C; Mármol Vázquez, P; Ramos Solís, M F

    2016-01-01

    Chronic venous insufficiency of the lower limbs is very prevalent. In recent decades, Doppler ultrasound has become the method of choice to study this condition, and it is considered essential when surgery is indicated. This article aims to establish a method for the examination, including venous mapping and preoperative marking. To this end, we review the venous anatomy of the lower limbs and the pathophysiology of chronic venous insufficiency and explain the basic hemodynamic concepts and the terminology required to elaborate a radiological report that will enable appropriate treatment planning and communication with other specialists. We briefly explain the CHIVA (the acronym for the French term "cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire"=conservative hemodynamic treatment for chronic venous insufficiency) strategy, a minimally invasive surgical strategy that aims to restore correct venous hemodynamics without resecting the saphenous vein.

  9. Chronic studies evaluating the carcinogenicity of monomethylarsonic acid in rats and mice.

    PubMed

    Arnold, Lora L; Eldan, Michal; van Gemert, Marcia; Capen, Charles C; Cohen, Samuel M

    2003-08-28

    Monomethylarsonic acid (MMA) was administered in the diet of male and female Fischer F344 rats and B6C3F1 mice in 2-year feeding studies according to US EPA guidelines. Rats were treated with 50, 400, or 1300 ppm MMA and mice were treated with 10, 50, 200, or 400 ppm MMA based on preliminary short-term studies. The highest dose in the male and female rat groups was reduced to 1000 ppm during week 53 and then further reduced to 800 ppm during week 60 due to high mortality in the male rats. There was no treatment-related mortality in the mice. The primary target organ for MMA-induced toxicity in rats and mice was the large intestine. Toxicity was more severe in rats compared to mice and in male rats compared to female rats. The maximum tolerated dose for chronic dietary administration of MMA in rats and mice was assessed as 400 ppm, and the no effect level with regard to intestinal toxicity was assessed as 50 ppm for rats and female mice and 200 ppm for male mice. There were no treatment-related neoplastic effects detected in either the rat or the mouse.

  10. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia.

    PubMed

    Moreno, Carol; Montillo, Marco; Panayiotidis, Panayiotis; Dimou, Maria; Bloor, Adrian; Dupuis, Jehan; Schuh, Anna; Norin, Stefan; Geisler, Christian; Hillmen, Peter; Doubek, Michael; Trněný, Marek; Obrtlikova, Petra; Laurenti, Luca; Stilgenbauer, Stephan; Smolej, Lukas; Ghia, Paolo; Cymbalista, Florence; Jaeger, Ulrich; Stamatopoulos, Kostas; Stavroyianni, Niki; Carrington, Patrick; Zouabi, Hamadi; Leblond, Veronique; Gomez-Garcia, Juan C; Rubio, Martin; Marasca, Roberto; Musuraca, Gerardo; Rigacci, Luigi; Farina, Lucia; Paolini, Rossella; Pospisilova, Sarka; Kimby, Eva; Bradley, Colm; Montserrat, Emili

    2015-04-01

    We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.

  11. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia

    PubMed Central

    Moreno, Carol; Montillo, Marco; Panayiotidis, Panayiotis; Dimou, Maria; Bloor, Adrian; Dupuis, Jehan; Schuh, Anna; Norin, Stefan; Geisler, Christian; Hillmen, Peter; Doubek, Michael; Trněný, Marek; Obrtlikova, Petra; Laurenti, Luca; Stilgenbauer, Stephan; Smolej, Lukas; Ghia, Paolo; Cymbalista, Florence; Jaeger, Ulrich; Stamatopoulos, Kostas; Stavroyianni, Niki; Carrington, Patrick; Zouabi, Hamadi; Leblond, Veronique; Gomez-Garcia, Juan C.; Rubio, Martin; Marasca, Roberto; Musuraca, Gerardo; Rigacci, Luigi; Farina, Lucia; Paolini, Rossella; Pospisilova, Sarka; Kimby, Eva; Bradley, Colm; Montserrat, Emili

    2015-01-01

    We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39–85). Median number of prior lines of therapy was 4 (range 1–13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3–4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062. PMID:25596264

  12. Pilot study of a compassion meditation intervention in chronic pain

    PubMed Central

    Chapin, Heather L; Darnall, Beth D; Seppala, Emma M; Doty, James R; Hah, Jennifer M; Mackey, Sean C

    2016-01-01

    Background The emergence of anger as an important predictor of chronic pain outcomes suggests that treatments that target anger may be particularly useful within the context of chronic pain. Eastern traditions prescribe compassion cultivation to treat persistent anger. Compassion cultivation has been shown to influence emotional processing and reduce negativity bias in the contexts of emotional and physical discomfort, thus suggesting it may be beneficial as a dual treatment for pain and anger. Our objective was to conduct a pilot study of a 9-week group compassion cultivation intervention in chronic pain to examine its effect on pain severity, anger, pain acceptance and pain-related interference. We also aimed to describe observer ratings provided by patients’ significant others and secondary effects of the intervention. Methods Pilot clinical trial with repeated measures design that included a within-subjects wait-list control period. Twelve chronic pain patients completed the intervention (F= 10). Data were collected from patients at enrollment, treatment baseline and post-treatment; participant significant others contributed data at the enrollment and post-treatment time points. Results In this predominantly female sample, patients had significantly reduced pain severity and anger and increased pain acceptance at post-treatment compared to treatment baseline. Significant other qualitative data corroborated patient reports for reductions in pain severity and anger. Conclusions Compassion meditation may be a useful adjunctive treatment for reducing pain severity and anger, and for increasing chronic pain acceptance. Patient reported reductions in anger were corroborated by their significant others. The significant other corroborations offer a novel contribution to the literature and highlight the observable emotional and behavioral changes in the patient participants that occurred following the compassion intervention. Future studies may further examine how

  13. What's Eating Gilbert Grape?: A Case Study of Chronic Illness

    ERIC Educational Resources Information Center

    Alexander, Matthew; Waxman, Dael; White, Patricia

    2006-01-01

    Cinemeducation refers to the use of movies or movie clips to educate learners about the psychosocial aspects of health care. This paper describes the use of a clip from the movie, "What's Eating Gilbert Grape?" to teach medical students about chronic illness. The clip is used to set up a case study based on the lead character, Gilbert…

  14. Broccoli seed extract: Genotoxicity and subchronic toxicity studies.

    PubMed

    Zhou, Yu; Yang, Hui; Li, Yongning; Lynch, B; Jia, Xudong

    2015-10-01

    Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product. PMID:26271574

  15. [Advance in study on zearalenone's toxicity and determination].

    PubMed

    He, Qing-Hua; Xu, Yang

    2005-07-01

    The article is intended to introduce the zearalenone's toxicity, determination methods and prevention. Zearalenone is one of the most widely distributed mycotoxins produces by Fusarium Species, it is harm to animals and human. And it can induce human liver cancer,carcinoma of tesis esophagus cancer. Now we use high-performance liquid chromatography, gas chromatography, thin layer chromatography, non-toxicity determinations to detect it.

  16. Sub-chronic Administration of Methanolic Whole Fruit Extract of Lagenaria breviflora (Benth.) Roberty Induces Mild Toxicity in Rats

    PubMed Central

    Olorunnisola, Olubukola Sinbad; Afolayan, Anthony Jide; Adetutu, Adewale

    2015-01-01

    Background: The effect of the methanolic whole fruit extract from Lagenaria breviflora on vital organs and antioxidant enzymes was investigated in this study. Materials and Methods: L. breviflora (250, 500 and 1000 mg/kg/b.w.t./day/rat) was fed orally with the cannula to male albino rats for 28 days. At the end of the treatment, the rats were sacrificed and the effect of the extract on histology of the liver, heart, lipid peroxidation, tissue and serum antioxidant enzymes (superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase) activities, glutathione, myocardial marker enzymes (creatine kinase [CK], lactate dehydrogenase [LDH], alanine transaminase [ALT], and aspartate transaminase [AST]) in serum, and heart homogenate were assessed. Results: The extract demonstrated mild organ doses dependent (500 and 1000 mg/kg) pathological alterations in the architectural section of the liver and heart. At 250 mg/kg/b.w.t., the extract caused a significant (P < 0.05) increase in the level of thiobarbituric reacting acids substance and antioxidant enzyme activities, but causes (P < 0.05) decrease in serum and tissue antioxidant capacity at 500 and 1000 mg/kg/b.w.t., respectively. Also on these two doses, a significant (P < 0.05) increase in serum activity of CK, LDH, ALT, and AST and concomitantly decrease (P < 0.05) in heart homogenate were also observed. Conclusion: The results suggested that the Fruit of L. breviflora may contain phytotoxic Substances(s) which may be hepatotoxic, cardiotoxic or able to induce oxidative stress at high concentration. Hence, the consumption of the plant should be taken with caution. SUMMARY Methanolic whole fruit extract from Lagenaria breviflora demonstrate dose dependent mild toxicity on vital organs (Heart and liver) and anti-oxidant enzymes. The fruit of Lagenaria breviflora may contain Phyto-toxic substance (s) which may be hepatotoxic, Cardio-toxic or able to induce oxidative stress at high concentration. Hence

  17. Chronic toxicity of erythromycin thiocyanate to Daphnia magna in a flow-through, continuous exposure test system

    USGS Publications Warehouse

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

    2011-01-01

    Approval of a new animal drug application for AQUAMYCIN 100?? (erythromycin thiocyanate; ET) to treat freshwater salmonid species with bacterial kidney disease is being pursued in the US. As part of the approval process, ETs impact on an aquatic environment had to be described in an environmental assessment. The environmental assessment was lacking data to characterize the effect ET would have on a chronically exposed aquatic invertebrate organism. A major step to fulfilling the environmental assessment was completed after conducting a comprehensive study continuously exposing Daphnia magna to ET for 21 days. Results indicated that the no observable effect concentration for ET was 179 ??g/L. ?? 2011 Springer Science+Business Media, LLC (outside the USA).

  18. Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database

    EPA Science Inventory

    Thirty years of pesticide registration toxicity data have been historically stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA) . A significant portion of these data have now been processed into standardized and structured toxicity data with...

  19. Ecotoxicological studies of environmental samples from Buenos Aires area using a standardized amphibian embryo toxicity test (AMPHITOX).

    PubMed

    Herkovits, Jorge; Perez-Coll, Cristina; Herkovits, Francisco D

    2002-01-01

    The toxicity of 34 environmental samples from potentially polluted and reference stations were evaluated by means of the AMPHITOX test from acute to chronic exposure according to the toxicity found in each sample. The samples were obtained from surface and ground water, leaches, industrial effluents and soils. The data, expressed in acute, short-term chronic and chronic Toxicity Units (TUa, TUstc and TUc) resulted in a maximal value of 1000 TUc, found in a leach, while the lower toxicity value was 1.4 TUa corresponding to two surface water samples. In five samples (four providing from reference places) no toxicity was detected. The results point out the possibility of evaluating the toxicity of a wide diversity of samples by means of AMPHITOX as a customized toxicity test. The fact that almost all samples with suspected toxicity in rivers and streams from the Metropolitan area of Buenos Aires city resulted toxic, indicates the need of enhanced stewardship of chemical substances for environmental and human health protection purposes. PMID:11808551

  20. Experimental studies on the toxicity of lithographic developer solution.

    PubMed

    Saito, T; Takeichi, S

    1995-01-01

    The purpose of this study was to determine whether the toxicity of a lithographic developer solution which contains hydroquinone is caused by hydroquinone or the alkaline lithographic developer solution. Male Wistar rats were divided into seven groups. In four groups, rats were dosed orally with 3% hydroquinone or 3% hydroquinone in 3% lithographic developer solution. Hydroquinone levels were measured after one and 24 hours. In two groups, rats were dosed orally with 6% hydroquinone or 6% hydroquinone in lithographic developer solution. In the seventh group, rats received the alkaline solution only. Hydroquinone measurement was made using gas chromatography-mass spectrometry. Hydroquinone was rapidly absorbed from the gastrointestinal tract and subsequently distributed throughout the body. Nearly all hydroquinone was excreted in the urine as either a glucuronide or a sulfate (78-82%) within 24 hours. All rats administered 6% hydroquinone in non-alkaline vehicle died, but the mortality rate of rats administered 6% hydroquinone in lithographic developer solution was 60%. Tissue hydroquinone was lower at one hour and 24 hours after administration in lithographic developer solution than in equal dose of hydroquinone in non-alkaline vehicle suggesting decreased absorption in an alkaline pH. Hydroquinone was not associated with gross pathologic changes of the intestine but all animals treated with lithographic developer solution or alkaline solution had congestion, hemorrhagic petechiae and purple-brown discoloration throughout the small intestine. The combination of alkaline/formaldehyde diluent with hydroquinone may delay hydroquinone absorption but increase the risk of intestinal necrosis.

  1. Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

    PubMed Central

    Elshama, Said Said; EL-Kenawy, Ayman El-Meghawry; Osman, Hosam-Eldin Hussein

    2016-01-01

    Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose. PMID:26941796

  2. Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats.

    PubMed

    Elshama, Said Said; El-Kenawy, Ayman El-Meghawry; Osman, Hosam-Eldin Hussein

    2016-01-01

    Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose. PMID:26941796

  3. Studies of toxic aerosols via elastic and inelastic light scattering

    SciTech Connect

    Foss, W.; Li, W.; Allen, T.M.; Blair, D.S.; Davis, E.J. )

    1993-02-01

    Evaporation rates and chemical characteristics of potentially toxic aerosols have been determined by elastic and inelastic light-scattering measurements. The aerosol systems examined were a commercial catalyst consisting of a mixture of stannous octanoate (SNO) and 2-ethylhexanoic acid (EHA) and droplets emitted from open tanks of chromic acid solutions used for anodizing aluminum. The heavy metals contained in these aerosols represent a danger to the workplace if such materials are inhaled. Nanogram amounts of the solutions were studied by suspending single microdroplets in electrodynamic balances in a flow of air to measure evaporation rates and to obtain Raman spectra. Elastic scattering data include phase functions and morphological resonance spectra from which droplet sizes are determined. The inelastic light-scattering data or Raman spectra provide molecular vibrational bond information. It was found that EHA spectra agree with bulk data in the literature, and that SNO Raman spectra, which are not available in the literature, are consistent with infrared spectra for bulk SNO. At room temperature the vapor pressure of SNO is on the order of 0.01 Pa while that of EHA is on the order of 0.1 Pa. Raman data for the residue of evaporated chromic acid solutions show the presence of chromium oxides (Cr[sup 6+] compounds), surfactants, and bound (nonvolatile) water. 31 refs., 14 figs.

  4. Clinical toxicity study of Semecarpus anacardium Linn. f.

    PubMed

    Murty, G K

    1974-09-01

    Semecarpus anacardium was administered to 266 cases in 3 formulations: Amrit Bhallatak (186 cases), RB 3 (48 cases), and Garsin (32 cases). The Amrit Bhallatak is a compound formulation containing extract of both the cotyledons and the pericarp of the fruit of Semecarpus anacardium. RB3 is composed of the whole cotyledon (300 mg); the daily dose of cotyledons was 3.6 g. Garsin contained 200 g of cotyledons. The extract is derived by separating the oil by a physical process. The daily dosage of Amrit Bhallatak was 10 g/day, that of Garsin, 2.4 g/day. No toxicity or side effects were observed. The therapeutic value of Semecarpus anacardium in arthropathies, atopic dermatitis, leucoderma, leprosy, hypothyroidism, oligospermia, and azoospermia and its value as an oral contraceptive have been studied. The most significant effect was on the ovaries and testes. The drug probably acts via the hypophysics. Out of 266 patients, 189 were men, 77 women between 30-45 years of age. The treatment was restricted to internal medication by mouth. No external contact or application of the drug was applied. Of the 77 women treated with the drug, 41 were followed up after treatment. 12 had become pregnant and none showed any teratogenecity.

  5. 13-week oral toxicity study of vinyl laurate in rats.

    PubMed

    Lina, Ben A R; Messinger, Horst; Bär, Albert

    2015-02-01

    Vinyl laurate (VL) is used as a monomer in the production of polyvinyl acetate vinyl laurate copolymer, a component of chewing gum base. The safety of VL was examined in a 13-week oral toxicity study in Wistar rats. VL was administered in corn coil by daily gavage (5 ml/kg bw/d) to four main groups (10 rats/sex) at doses of 0 (vehicle only), 50, 250 and 1000 mg/kg bw/d, respectively. The control and high-dose group comprised an additional 5 rats/sex which were kept untreated for a further 4 weeks until sacrifice (recovery groups). In addition to standard parameters, male and female fertility parameters were determined as well. There were no mortalities and treatment-related clinical signs. Neurobehavioral observations and motor activity assessment, ophthalmoscopic examinations, body weights, feed and water intakes, blood cell counts, coagulation time, standard clinical chemical parameters and urinalyses, absolute and relative organ weights at the end of the treatment as well as macroscopic examination at necropsy and microscopic examination of standard organs and tissues did not show any treatment-related changes. Female and male fertility parameters (estrus cyclicity, testicular and epididymal sperm counts, sperm motility and morphology) were not affected by the treatment. Accordingly, the no-observed-adverse-effect level (NOAEL) for VL was determined to be 1000 mg/kg bw/d, i.e. the highest dose level tested. PMID:25445296

  6. Short-term toxicity studies of loline alkaloids in mice.

    PubMed

    Finch, S C; Munday, J S; Munday, R; Kerby, J W F

    2016-08-01

    Epichloë endophytes have been used successfully in pastoral systems to reduce the impact of insect pests through the expression of secondary metabolites. The use of endophytes could be extended to other plant species, such as cereal crops, where the production of bioactive secondary metabolites would reduce the reliance on pesticides for insect control. The success of this approach is dependent on the selection of an appropriate secondary metabolite target which must not only be effective against insect pests but also be safe for grazing and monogastric animals. The loline alkaloids have been identified as possible target metabolites as they are associated with potent effects on insects and low toxicity to grazing animals. The purpose of the current study was to generate toxicological data on the loline alkaloids in a monogastric system using mice. Male and female mice were fed 415 mg/kg/day total lolines for a 3-week period. The loline treatment caused no statistically significant effect on gross pathology, histology, haematology, blood chemistry, heart rate, blood pressure or motor coordination. Reduced weight gain and food consumption were noted in the loline groups during the initial stages of the experiment. This experiment raises no food safety concerns for the loline alkaloids. PMID:27276360

  7. [Chronic disease impact on partners. An explorative study].

    PubMed

    Pacini, G; Sarmiento, I

    2008-01-01

    In the last years there has been a growing interest of researchers for themes dealing with chronic illness and issues related to that condition. Several authors have studied the difficulties caregivers have to cope with, especially when the patient's partner has this role. That condition would have both physical and psychological consequences, but its real effects seem to depend on a complex set of interacting elements. On the basis of these researches, in the current study we aimed to explore the influence of adult attachment and marital satisfaction on the impact that chronic illness can have on patient's partner and on his/her health-related quality of life. The sample is composed of 40 chronic renal failure patients' partner-caregivers. Each caregiver filled in a battery of tests for finding out the characteristics of adult attachment and marital satisfaction, health-related quality of life and the association between these variables and the impact of chronic illness on partners. Descriptive statistics, correlations and one-sample t test analysis have been performed. Results show a significant correlation between attachment style and caregiving burden; there are no gender differences in disease impact on caregiver. Moreover caregivers seem to have a worse quality of life in comparison to general population. Understanding caregiving can lead, at a future time, to planning specific interventions for both patients and partners, using a global and integrated approach that respects individuals and couples in their biologic, psychological and relational dimensions. PMID:19288778

  8. Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease

    PubMed Central

    Karoli, Yogesh; Fatima, Jalees; Manhar, Mohammad

    2016-01-01

    Introduction Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. Aim To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. Materials and Methods This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). Results A total of 72 patients with mean age 50.04±11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. Conclusion Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver

  9. Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes.

    PubMed

    Garrett, B J; Cheeke, P R; Miranda, C L; Goeger, D E; Buhler, D R

    1982-02-01

    Effect of dietary tancy ragwort (Senecio jacobaea), comfrey (Symphytum officinale), bracken (Pteridium aquilinum) and alfalfa (Medicago sativa) on hepatic drug-metabolizing enzymes in rats were measured. Tansy ragwort and bracken increased (P less than 0.05) the activity of glutathione transferase and epoxide hydrolase. Comfrey and alfalfa increased (P less than 0.05) the activity of aminopyrine N-demethylase. Feeding bracken or St. John's wort (Hypericum perforatum) in conjunction with tansy ragwort did not influence chronic toxicity of tansy ragwort as assessed by rat survival time. Dietary tansy ragwort resulted in increased (P less than 0.05) hepatic copper levels; the other plants did not affect copper levels. The results do not suggest any major interaction in the toxicity of tansy ragwort with bracken or St. John's wort. PMID:7080084

  10. Development of a chronic, early life-stage sub-lethal toxicity test and recovery assessment for the tropical zooxanthellate sea anemone Aiptasia pulchella.

    PubMed

    Howe, Pelli L; Reichelt-Brushett, Amanda J; Clark, Malcolm W

    2014-02-01

    There is an urgent need to identify additional tropical marine species and develop sensitive sub-lethal and chronic toxicity test methods for routine ecotoxicology. The tropical symbiotic sea anemone Aiptasia pulchella is a suitable species for use in ecotoxicology and here we have assessed the effects of trace metal exposures on the development of asexually produced A. pulchella pedal lacerates to a juvenile stage. Concentrations of 55 µg/L for cadmium, 262 µg/L for cobalt, 5 µg/L for copper, and 269 µg/L for zinc were estimated to inhibit normal development by 50 percent after 8-d exposures, and are among the most sensitive available toxicity estimates for marine organisms. This work illustrates the potential value of this species and sub-lethal toxicological endpoint for routine ecotoxicology in tropical marine environments.

  11. Study of acute toxicity of Ukrain in rats after intravenous injection.

    PubMed

    Kulik, G I; Deneka, E R; Todor, I N; Karmozina, L G

    1998-01-01

    The acute toxicity of i.v. Ukrain injection in rats was studied. The interrelation between toxicity (death of animals) and dosage was determined by nonlinear regression method. White blood count (WBC) in peripheral blood, weight of animals, and weight of major organs were determined in animals during all stages of investigation. Morphological studies of toxic changes in 40 different organs of rats were performed on macro- and microscopic levels.

  12. Toxicity of ozone and nitrogen dioxide to alveolar macrophages: comparative study revealing differences in their mechanism of toxic action

    SciTech Connect

    Rietjens, I.M.; Poelen, M.C.; Hempenius, R.A.; Gijbels, M.J.; Alink, G.M.

    1986-01-01

    In this study the toxic mechanisms of action of ozone and nitrogen dioxide were compared using an intact cell model. Rat alveolar macrophages were exposed by means of gas diffusion through a Teflon film. In this in vitro system, ozone appeared to be 10 times more toxic than nitrogen dioxide. alpha-Tocopherol protected equally well against ozone and nitrogen dioxide. It was demonstrated that alpha-tocopherol provided its protection by its action as a radical scavenger and not by its stabilizing structural membrane effect, as (1) concentrations of alpha-tocopherol that already provided optimal protection against ozone and nitrogen dioxide did not influence the membrane fluidity of alveolar macrophages and (2) neither one of the structural alpha-tocopherol analogs tested (phytol and the methyl ether of alpha-tocopherol) could provide a protection against ozone or nitrogen dioxide comparable to the one provided by alpha-tocopherol. It was concluded that reactive intermediates scavenged by alpha-tocopherol are important in the toxic mechanism of both ozone and nitrogen dioxide induced cell damage. However, further results presented strongly confirmed that the kind of radicals and/or reactive intermediates, and thus the toxic reaction mechanism involved, must be different in ozone- and nitrogen dioxide-induced cell damage. This was concluded from the observations that showed that (1) vitamin C provided significantly better protection against nitrogen dioxide than against an equally toxic dose of ozone, (2) glutathione depletion affected the cellular sensitivity toward ozone to a significantly greater extent than the sensitivity towards nitrogen dioxide, and (3) the scavenging action of alpha-tocopherol was accompanied by a significantly greater reduction in its cellular level during nitrogen dioxide exposure than during exposure to ozone.

  13. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    PubMed

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child). PMID:26511087

  14. Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

    PubMed

    Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

    2016-01-01

    Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

  15. Quantitative structure-toxicity relationship (QSTR) studies on the organophosphate insecticides.

    PubMed

    Can, Alper

    2014-11-01

    Organophosphate insecticides are the most commonly used pesticides in the world. In this study, quantitative structure-toxicity relationship (QSTR) models were derived for estimating the acute oral toxicity of organophosphate insecticides to male rats. The 20 chemicals of the training set and the seven compounds of the external testing set were described by means of using descriptors. Descriptors for lipophilicity, polarity and molecular geometry, as well as quantum chemical descriptors for energy were calculated. Model development to predict toxicity of organophosphate insecticides in different matrices was carried out using multiple linear regression. The model was validated internally and externally. In the present study, QSTR model was used for the first time to understand the inherent relationships between the organophosphate insecticide molecules and their toxicity behavior. Such studies provide mechanistic insight about structure-toxicity relationship and help in the design of less toxic insecticides.

  16. Laboratory studies on antimycin A as a fish toxicant

    USGS Publications Warehouse

    Berger, Bernard L.; Lennon, Robert E.; Hogan, James W.

    1969-01-01

    Liquid and sand formulations of antimycin A were tested in laboratory waters of various temperature, hardness, pH, and turbidity against 31 species of fresh-water fish of various sizes and life stages. Each formulation of toxicant was lethal under all water conditions to fish eggs, fry, fingerlings, and adult fish. Trouts are the most sensitive and catfishes the least sensitive. Of the 31 species, 24 succumb to 5 p.p.b. or less of the toxicant; only certain catfishes survive 25 p.p.b, The order of toxicity to various species of fish suggests that antimycin has possibilities for selective or partial control of certain unwanted fish. Although toxic to fish under ice, antimycin is more active in warm water than in cold. It is slightly more active in soft water than in hard; it is more active and persists far longer in water at pH 5 to 8 than at pH 9 or 10. It is active on fish in either clear and turbid waters, and it can be detoxified by potassium permanganate, The results contributed to registration of antimycin A in Fintrol-5 formulation as a fish toxicant.

  17. Standard operating procedures for conducting acute and chronic aquatic toxicity tests with Eurytemora affinis, a calanoid copepod

    SciTech Connect

    Ziegenfuss, M.C.; Hall, L.W.

    1998-10-01

    Eurytemora affinis, a calanoid copepod, was selected for standard toxicity testing protocol development subsequent to screening 25 resident Chesapeake Bay species including fish, invertebrates, and plants. Eurytemora was selected because of its ecological importance as an essential component in the trophic structure of the estuary, its relative practicability of culturing in the laboratory for year-round availability, and its sensitivity to toxic substances. The standards operating procedures described in this document provide detailed procedures for culturing, holding, and toxicity testing of E. affinis.

  18. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, Ning; Mebane, Christopher A.; Kunz, James L.; Ingersoll, Christopher G.; Brumbaugh, William G.; Santore, Robert C.; Gorsuch, Joseph W.; Arnold, W. Ray

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10 mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10 mg C/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100 mg/L as CaCO3, pH 8.3, DOC 0.5 mg C/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15–72 μg Cu/L) for mussel survival in 4-d exposures and increased about 11-fold (25–267 μg Cu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10 mg C/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13–61 μg Cu/L for survival; 8.8–38 μg Cu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13–215 μg Cu/L) for survival or approximately fourfold (12–42 μg Cu/L) for reproduction across DOC concentrations from 0.5 to 10 mg C/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10 mg C/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and

  19. Influence of dissolved organic carbon on toxicity of copper to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) in acute and chronic water exposures

    USGS Publications Warehouse

    Wang, N.; Mebane, C.A.; Kunz, J.L.; Ingersoll, C.G.; Brumbaugh, W.G.; Santore, R.C.; Gorsuch, J.W.; Arnold, W.R.

    2011-01-01

    Acute and chronic toxicity of copper (Cu) to a unionid mussel (Villosa iris) and a cladoceran (Ceriodaphnia dubia) were determined in water exposures at four concentrations of dissolved organic carbon (DOC; nominally 0.5, 2.5, 5, and 10mg/L as carbon [C]). Test waters with DOC concentrations of 2.5 to 10mgC/L were prepared by mixing a concentrate of natural organic matter (Suwannee River, GA, USA) in diluted well water (hardness 100mg/L as CaCO3, pH 8.3, DOC 0.5mgC/L). Acute median effect concentrations (EC50s) for dissolved Cu increased approximately fivefold (15-72??gCu/L) for mussel survival in 4-d exposures and increased about 11-fold (25-267??gCu/L) for cladoceran survival in 2-d exposures across DOC concentrations from 0.5 to 10mgC/L. Similarly, chronic 20% effect concentrations (EC20s) for the mussel in 28-d exposures increased about fivefold (13-61??gCu/L for survival; 8.8-38??gCu/L for biomass), and the EC20s for the cladoceran in 7-d exposures increased approximately 17-fold (13-215??gCu/L) for survival or approximately fourfold (12-42??gCu/L) for reproduction across DOC concentrations from 0.5 to 10mgC/L. The acute and chronic values for the mussel were less than or approximately equal to the values for the cladoceran. Predictions from the biotic ligand model (BLM) used to derive the U.S. Environmental Protection Agency's ambient water quality criteria (AWQC) for Cu explained more than 90% of the variation in the acute and chronic endpoints for the two species, with the exception of the EC20 for cladoceran reproduction (only 46% of variation explained). The BLM-normalized acute EC50s and chronic EC20s for the mussel and BLM-normalized chronic EC20s for the cladoceran in waters with DOC concentrations of 2.5 to 10mgC/L were equal to or less than the final acute value and final chronic value in the BLM-based AWQC for Cu, respectively, indicating that the Cu AWQC might not adequately protect the mussel from acute and chronic exposure, and the cladoceran

  20. Prenatal development toxicity study of zinc oxide nanoparticles in rats

    PubMed Central

    Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Meyoung-Kon; Jeong, Jayoung; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

    2014-01-01

    This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. PMID:25565834

  1. Prenatal development toxicity study of zinc oxide nanoparticles in rats.

    PubMed

    Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Meyoung-Kon; Jeong, Jayoung; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

    2014-01-01

    This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnO(SM20(+)) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague-Dawley rats. ZnO(SM20(+)) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnO(SM20(+)) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. PMID:25565834

  2. Analgesics as Reinforcers with Chronic Pain: Evidence from Operant Studies

    PubMed Central

    Ewan, Eric E.; Martin, Thomas J.

    2013-01-01

    Previously preclinical pain research has focused on simple behavioral endpoints to assess the efficacy of analgesics in acute and chronic pain models, primarily reflexive withdrawal from an applied mechanical or thermal stimulus. However recent research has been aimed at investigating other behavioral states in the presence of pain, including spontaneous, non-elicited pain. One approach is to investigate the reinforcing effects of analgesics in animals with experimental pain, which should serve as reinforcers by virtue of their ability to alleviate the relevant subjective states induced by pain. The gold standard for assessing drug reinforcement is generally accepted to be drug self-administration, and this review highlights the ability of drugs to serve as reinforcers in animals with experimental neuropathic pain, and the extent to which this behavior is altered in chronic pain states. Additionally, intracranial self-stimulation is an operant procedure that has been used extensively to study drug reinforcement mechanisms and the manner in which neuropathic pain alters the ability of drugs to serve as reinforcers in this paradigm will also be discussed. Drug self-administration and intracranial self-stimulation have promise as tools to investigate behavioral effects of analgesics in animals with chronic pain, particularly regarding the mechanisms through which these drugs motivate consumption in a chronic pain state. PMID:23973302

  3. Balneotherapy for chronic low back pain: a randomized, controlled study.

    PubMed

    Kesiktas, Nur; Karakas, Sinem; Gun, Kerem; Gun, Nuran; Murat, Sadiye; Uludag, Murat

    2012-10-01

    A large number of treatments were used for patients with chronic low back pain. Frequent episodes have been reported very high. Although balneotherapy was found effective in this disease, there are not well-designed studies. We aimed to determine the effectiveness of balneotherapy versus physical therapy in patients with chronic low back pain. Exercise was added to both treatment programs. Sixty patients with chronic low back pain were randomly divided into two groups. Physical modalities plus exercise were applied to group 1, and group 2 was received balneotherapy plus exercise for ten sessions. The following parameters were measured: visual analogue scale at rest and movement for pain, paracetamol dose, manual muscle test for lumber muscles, modified Schoeber' test, Oswestry disability index, and Short-Form 36 at the beginning and end of the therapies and at the 3 months follow-up. The statistical analyses were performed using the SPSS 10.0 program. Both groups achieved significant improvements within themselves. But balneotherapy groups were improved at back extensor muscle test (P < 0.05), modified Schoeber's test (P < 0.03), Oswestry disability index, and the some scores of SF 36 (energy vitality, social function, role limitations related to physical problems, and general health P < 0.05). Balneotherapy combined with exercise therapy had advantages than therapy with physical modalities plus exercise in improving quality of life and flexibility of patients with chronic low back pain.

  4. Toxicity and teratogenicity studies with the hypolipidemic drug RMI 14,514 in rats.

    PubMed

    Gibson, J P; Larson, E J; Yarrington, J T; Hook, R H; Kariya, T; Blohm, T R

    1981-01-01

    The hypolipidemic drug RMI 14,514 (5-tetradecyloxy-2-furoic acid) has an oral LD50 of over 5000 mg/kg in rats. In a chronic toxicity study (6 months drug diet) doses of 30, 100, or 300 mg/kg/day produced no obvious signs of toxicity or abnormal clinical pathology parameters, other than prominent growth retardation at 300 mg/kg, which was somewhat alleviated when the dose was reduced to 200 mg/kg after 6 weeks. Hepatic change in the form of mild lipid accumulation was noted histopathologically after 6 months of treatment at 100 or 300 mg/kg/day, but was not present at 3 months or after 4 weeks off drug. The administration of RMI 14,514 in the diet to pregnant rats at 30, 100, or 150 mg/kg/day on Days 7 thru 21 of pregnancy (day 1 = day sperm detected) did not induce any teratogenic effects. When rats were exposed to the drug from implantation thru sexual maturity (126 days of age) at the same dosage, it produced no adverse developmental or behavioral effects, except for slight reduction in weight gain from birth to sexual maturity at 150 mg/kg/day. The drug caused reductions in plasma cholesterol and total fatty acids, but no distinct changes in various tissue lipids, except in the erythrocyte where fatty acids and phospholipids were reduced. These differences did not affect membrane integrity of the erythrocyte as far as osmotic or mechanical fragility tests could determine. The drug, which bears a structural resemblance to long-chain fatty acids, was incorporated into tissue lipids in detectable amounts, but tended to disappear from tissues at a rate similar to that of expected lipid turnover after treatment was stopped.

  5. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  6. A 24-Weeks Toxicity Study of Eryngium foetidum Linn. Leaves in Mice.

    PubMed

    Janwitthayanuchit, Kanittha; Kupradinun, Piengchai; Rungsipipat, Anudep; Kettawan, Aikkarach; Butryee, Chaniphun

    2016-07-01

    Eryngium foetidum Linn. leaves (EF) are widely used in Thailand and many countries throughout Asia as a culinary seasoning and a traditional medicine. However, adverse effect of high dose consumption in long duration has not been evaluated. The aim of this study was to investigate chronic toxicity of EF in mice. Thirty-two ICR male mice were divided into 4 groups of 8 mice each. The mice were fed AIN-76 rodent diet, or AIN-76 rodent diet supplemented with ground freeze-dried EF at 0.8%, 1.6% and 3.2% that is equivalent to approximately 35, 73 and 155 times that of human consumption, respectively, at 97.5 percentile for a period of 24 weeks. At the end of experiment, the mice were euthanized and blood samples were collected for hematological and biochemical evaluations. Necropsy was performed while visceral organs such as lung, liver, kidneys, spleen etc. were collected, weighed and histopathologically examined. Blood urea nitrogen (BUN) results of mice in 1.6% and 3.2% EF diet groups were significantly higher than the BUN of control group. No significant difference was noted in other biochemical and hematological properties between the treatment groups and control; all results were within normal range. Histopathology of almost all visceral organs showed no significant changes. However, tubulonephrosis and chronic interstitial nephritis were observed in the groups treated with 1.6% and 3.2% EF diet. Body weight was reduced significantly at week 12 to week 20 when compared to the control group while relative kidney weights were significantly increased. In conclusion, the consumption of EF in diet at high doses illustrated the adverse effect on some biochemical parameters and histopathology in mice. Our findings suggested that EF daily consumption for 24 weeks, at higher doses than the 0.8% EF diet (35 times of human consumption), might cause adverse effect on kidney function in mice. PMID:27437090

  7. A 24-Weeks Toxicity Study of Eryngium foetidum Linn. Leaves in Mice

    PubMed Central

    Janwitthayanuchit, Kanittha; Kupradinun, Piengchai; Rungsipipat, Anudep; Kettawan, Aikkarach; Butryee, Chaniphun

    2016-01-01

    Eryngium foetidum Linn. leaves (EF) are widely used in Thailand and many countries throughout Asia as a culinary seasoning and a traditional medicine. However, adverse effect of high dose consumption in long duration has not been evaluated. The aim of this study was to investigate chronic toxicity of EF in mice. Thirty-two ICR male mice were divided into 4 groups of 8 mice each. The mice were fed AIN-76 rodent diet, or AIN-76 rodent diet supplemented with ground freeze-dried EF at 0.8%, 1.6% and 3.2% that is equivalent to approximately 35, 73 and 155 times that of human consumption, respectively, at 97.5 percentile for a period of 24 weeks. At the end of experiment, the mice were euthanized and blood samples were collected for hematological and biochemical evaluations. Necropsy was performed while visceral organs such as lung, liver, kidneys, spleen etc. were collected, weighed and histopathologically examined. Blood urea nitrogen (BUN) results of mice in 1.6% and 3.2% EF diet groups were significantly higher than the BUN of control group. No significant difference was noted in other biochemical and hematological properties between the treatment groups and control; all results were within normal range. Histopathology of almost all visceral organs showed no significant changes. However, tubulonephrosis and chronic interstitial nephritis were observed in the groups treated with 1.6% and 3.2% EF diet. Body weight was reduced significantly at week 12 to week 20 when compared to the control group while relative kidney weights were significantly increased. In conclus