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 ...

Investigation of chronic toxicity of hydroxyapatite nanoparticles administered orally for one year in wistar rats.

PubMed

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2017-07-01

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

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...

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

Acute and chronic toxicity of soluble fractions of industrial solid wastes on Daphnia magna and Vibrio fischeri.

PubMed

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(CE(50,48 h) = 2.21%). A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE(50,30 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.

Dredged Material Analysis Tools; Performance of Acute and Chronic Sediment Toxicity Methods

DTIC Science & Technology

2008-04-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Research Program ERDC/EL TR-08-16 April 2008 Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity Methods Jeffery...potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of dredged material

Dredged Material Analysis Tools; Performance of Acute and Chronic Sediment Toxicity Methods

DTIC Science & Technology

2008-07-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Environmental Research Program ERDC/EL TR-08-16 July 2008 Revised Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity ...insight into the potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of

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—...

Development of a Complete Life Cycle Sediment Toxicity Test for the Sheepshead Minnow (Cyprinodon variegatus)

EPA Science Inventory

Existing sediment toxicity test methods are limited to acute and chronic exposure of invertebrates and acute exposure of vertebrates, with limited guidance on the chronic exposure of vertebrates, specifically fishes. A series of life stage-specific studies were conducted to dete...

AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

EPA Science Inventory

ABSTRACT
The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

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

PubMed

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

2016-02-01

Metabolomics has been widely applied to toxicological fields, especially to elucidate the mechanism of action of toxicity. In this review, metabolomics application with focus on the studies of chronic and acute toxicities of drugs of abuse like stimulants, opioids and the recently-distributed designer drugs will be presented in addition to an outline of basic analytical techniques used in metabolomics. Limitation of metabolomics studies and future perspectives will be also provided. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkataramiah, A.; Lakshmi, G.J.; Best, C.

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.

Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

PubMed

Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-02-01

Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to clothianidin, thereby likely enhancing toxicity. Environ Toxicol Chem 2017;36:372-382. © 2016 SETAC. © 2016 SETAC.

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. © 2015 SETAC.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.

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 ofmore » 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.« less

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

PubMed

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

2011-08-01

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

Chlorpyrifos chronic toxicity in broilers and effect of vitamin C.

PubMed

Kammon, A M; Brar, R S; Sodhi, S; Banga, H S; Singh, J; Nagra, N S

2011-01-01

An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw) (1/50 LD50) chlorpyrifos (Radar(®)), produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

20180312 - Reproducibility and variance of liver effects in subchronic and chronic repeat dose toxicity studies (SOT)

EPA Science Inventory

In vivo studies provide reference data to evaluate alternative methods for predicting toxicity. However, the reproducibility and variance of effects observed across multiple in vivo studies is not well understood. The US EPA’s Toxicity Reference Database (ToxRefDB) stores d...

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. © 2015 SETAC.

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

EPA Science Inventory

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

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

PubMed

Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

2016-12-24

Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chronic toxicity of selected polycyclic aromatic hydrocarbons to algae and crustaceans using passive dosing.

PubMed

Bragin, Gail E; Parkerton, Thomas F; Redman, Aaron D; Letinksi, Daniel J; Butler, Josh D; Paumen, Miriam Leon; Sutherland, Cary A; Knarr, Tricia M; Comber, Mike; den Haan, Klaas

2016-12-01

Because of the large number of possible aromatic hydrocarbon structures, predictive toxicity models are needed to support substance hazard and risk assessments. Calibration and evaluation of such models requires toxicity data with well-defined exposures. The present study has applied a passive dosing method to generate reliable chronic effects data for 8 polycyclic aromatic hydrocarbons (PAHs) on the green algae Pseudokirchneriella subcapitata and the crustacean Ceriodaphnia dubia. The observed toxicity of these substances on algal growth rate and neonate production were then compared with available literature toxicity data for these species, as well as target lipid model and chemical activity-based model predictions. The use of passive dosing provided well-controlled exposures that yielded more consistent data sets than attained by past literature studies. Results from the present study, which were designed to exclude the complicating influence of ultraviolet light, were found to be well described by both target lipid model and chemical activity effect models. The present study also found that the lack of chronic effects for high molecular weight PAHs was consistent with the limited chemical activity that could be achieved for these compounds in the aqueous test media. Findings from this analysis highlight that variability in past literature toxicity data for PAHs may be complicated by both poorly controlled exposures and photochemical processes that can modulate both exposure and toxicity. Environ Toxicol Chem 2016;35:2948-2957. © 2016 SETAC. © 2016 SETAC.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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. © 2015 SETAC.

Toxicity of chromium (VI) to two mussels and an amphipod in water-only exposures with or without a co-stressor of elevated temperature, zinc, or nitrate

USGS Publications Warehouse

Wang, Ning; Kunz, James L.; Ivey, Chris D.; Ingersoll, Christopher G.; Barnhart, M. Christopher; Glidewell, Elizabeth A.

2017-01-01

The objectives of the present study were to develop methods for propagating western pearlshell (Margaritifera falcata) for laboratory toxicity testing and evaluate acute and chronic toxicity of chromium VI [Cr(VI)] to the pearlshell and a commonly tested mussel (fatmucket, Lampsilis siliquoidea at 20 °C or in association with a co-stressor of elevated temperature (27 °C), zinc (50 µg Zn/L), or nitrate (35 mg NO3/L). A commonly tested invertebrate (amphipod, Hyalella azteca) also was tested in chronic exposures. Newly transformed pearlshell (~1 week old) were successfully cultured and tested in acute 96 h Cr exposures (control survival 100%). However, the grow-out of juveniles in culture for chronic toxicity testing was less successful and chronic 28-day Cr toxicity tests started with 4 month-old pearlshell failed due to low control survival (39–68%). Acute median effect concentration (EC50) for the pearlshell (919 µg Cr/L) and fatmucket (456 µg Cr/L) tested at 20 °C without a co-stressor decreased by a factor of > 2 at elevated temperature but did not decrease at elevated Zn or elevated NO3. Chronic 28-day Cr tests were completed successfully with the fatmucket and amphipod (control survival 83–98%). Chronic maximum acceptable toxicant concentration (MATC) for fatmucket at 20 °C (26 µg Cr/L) decreased by a factor of 2 at elevated temperature or NO3 but did not decrease at elevated Zn. However, chronic MATC for amphipod at 20 °C (13 µg Cr/L) did not decrease at elevated temperature, Zn, or NO3. Acute EC50s for both mussels tested with or without a co-stressor were above the final acute value used to derive United States Environmental Protection Agency acute water quality criterion (WQC) for Cr(VI); however, chronic MATCs for fatmucket at elevated temperature or NO3 and chronic MATCs for the amphipod at 20 °C with or without elevated Zn or NO3 were about equal to the chronic WQC. The results indicate that (1) the elevated temperature increased the acute Cr toxicity to both mussel species, (2) fatmucket was acutely more sensitive to Cr than the pearlshell, (3) elevated temperature or NO3 increased chronic Cr toxicity to fatmucket, and (4) acute WQC are protective of tested mussels with or without a co-stressor; however, the chronic WQC might not protect fatmucket at elevated temperature or NO3 and might not protect the amphipod at 20 °C with or without elevated Zn or NO3.

Hepatic concentrations of copper and other metals in dogs with and without chronic hepatitis.

PubMed

Cedeño, Y; López-Alonso, M; Miranda, M

2016-12-01

Defects in copper metabolism have been described in several dog breeds, and recently, it has been suggested that changes in other essential trace elements could be involved in the pathogenesis of hepatic disease. This study measured hepatic copper accumulation and its interactions with other essential trace and toxic metals in dogs diagnosed with chronic hepatitis. Liver samples of 20 chronic hepatitis and 20 healthy dogs were collected. Samples were acid digested, and essential metals (cobalt, copper, iron, manganese, molibdenum, selenium and zinc) and toxic metals (arsenic, cadmium, mercury and lead) were analysed by inductively-coupled plasma mass spectrometry. Copper concentrations were significantly higher in dogs affected by hepatic disease than in controls. Dogs having chronic hepatitis with liver copper concentration greater than 100 mg/kg wet weight showed statistically higher cobalt, manganese and zinc concentrations than dogs having chronic hepatitis with liver copper concentrations less than 100 mg/kg wet weight and controls. Toxic metal concentrations were low - in all cases below the threshold associated with toxicity in dogs. Dogs with chronic hepatitis not only have increased concentrations of copper in the liver but also increased concentrations of cobalt, manganese and zinc; measurement of these elements may perhaps aid in diagnosis of liver disease in dogs. © 2016 British Small Animal Veterinary Association.

Toxic exposure to ethylene dibromide and mercuric chloride: effects on laboratory-reared octopuses.

PubMed

Adams, P M; Hanlon, R T; Forsythe, J W

1988-01-01

The effects of acute and chronic exposure to either ethylene dibromide (EDB) or mercuric chloride (MC) were studied in laboratory-reared Octopus joubini, O. maya and O. bimaculoides. The advantages of using octopuses were that the responses were immediate, highly visible and sensitive. All species demonstrated signs of toxicity to acute and chronic exposure to EDB and to MC. A dosage-sensitive relationship for the loss and subsequent recovery of locomotor response and of chromatophore expansion was found for each species after acute exposure. For each species the LC50 for chronic exposure occurred within 12 hr at 100 mg/l for EDB and within 3 hr at 1,000 mg/l for MC. This study demonstrated the potential usefulness of laboratory-reared octopuses in evaluating the toxicity of marine environmental pollutants.

76 FR 27256 - Saflufenacil; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... reflection of a mild and transient general systemic toxicity and not a substance- specific neurotoxic effect. In the subchronic neurotoxicity study, systemic toxicity (anemia), but no evidence of neurotoxicity... systemic toxicity in males. A LOAEL was not established for females. Chronic dietary (All populations...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.

In the present study, acute and chronic toxicities of five PAHs (naphthalene, anthracene, benz(a)anthracene, pyrene, and benzo(a)pyrene) and an oxygenated PAH derivative (anthrone) were determined in a terrestrial insect, Acheta domesticus (L.), with emphasis on the influence of route of entry on toxicity. Hexamethylphosphoric triamide (hempa) was included in the chronic tests since this chemosterilant is a useful reference compound for investigations of reproductive effects of chemicals in insects.

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

PubMed

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

Development of an acceptable factor to estimate chronic end points from acute toxicity data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venman, B.C.; Flaga, C.

1985-12-01

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 formore » an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.« less

PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: CONCEPT AND LINEAR REGRESSION

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from acute.toxicity data was developed in which simultaneous consideration is given to concentration, degree of response, and time course of effect. onsistent endpoint (lethality) and degree of response (O%) were used to com...

STATISTICAL APPROACH TO PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from cute toxicity data was developed in which simultaneous onsideration is given to concentration, degree of response, and ime course of effect. onsistent endpoint (lethality) and degree of response (0 percent) were used to...

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

PubMed

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

2018-04-15

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

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 exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route. PMID:24684892

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

PubMed

Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

2014-04-01

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. 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. 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. 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 exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.

Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 2

DTIC Science & Technology

1996-02-02

chronic, per {vascular Accumulation, foamy macrophage KIDNEY Mineralization Inf laomat ion, chronic Nephropathy Hydronephrosis Pyelonephritis...KIDNEY # EX Mineralization Inflammation, chronic Nephropathy Hydronephrosis Py»lonaphrItIs Hyperplasia, pelvic epithelium Pigmentation, cortex...Mineralization Inf Lajaaat ion, chronic Nephropathy Hydronephrosis Pigmentation, cor ten (1) - - - ɚ> (1) - ə> - (1) - ə> - 2L

Chronic ergot toxicity presenting with bilateral external iliac artery dissection and lower extremity rest pain.

PubMed

Molkara, Afshin M; Abou-Zamzam, Ahmed M; Teruya, Theodore H; Bianchi, Christian; Killeen, J David

2006-11-01

Chronic use of ergot alkaloids has been recognized as a rare cause of lower extremity ischemia. Most patients with ergot toxicity present with symptoms of lower extremity claudication. Herein we present a woman with bilateral lower extremity rest pain and a history of chronic ergot use for migraine headaches. Arteriography demonstrated extensive pruning of the distal arterial tree along with bilateral external iliac artery dissections - a finding that is not often associated with young, normotensive patients with chronic ergot toxicity. This patient was treated with endovascular stenting of the dissections along with cessation of ergot. Her symptoms improved markedly, and follow-up arteriography 6 weeks later demonstrated resolution of the iliac dissections along with restoration of nearly normal lower extremity runoff vessels. Discontinuation of ergot-containing products and cessation of tobacco and caffeine use is the cornerstone of therapy in chronic ergot toxicity. The association of ergot toxicity and iliac dissection has not been previously described. Endovascular or surgical interventions may be considered in patients with ergot toxicity for specific indications or those whose symptoms progress despite conservative management.

The Association Between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan.

PubMed

DeBeer, Bryann B; Davidson, Dena; Meyer, Eric C; Kimbrel, Nathan A; Gulliver, Suzy B; Morissette, Sandra B

2017-01-01

The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of chronic multisymptom illness (CMI). Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans' health is needed.

The Association between Toxic Exposures and Chronic Multisymptom Illness in Veterans of the Wars of Iraq and Afghanistan

PubMed Central

DeBeer, Bryann B.; Davidson, Dena; Meyer, Eric C.; Kimbrel, Nathan A.; Gulliver, Suzy B.; Morissette, Sandra B.

2017-01-01

Objective The purpose of this study was to determine if post-9/11 veterans deployed to the Iraq and Afghanistan conflicts experienced toxic exposures and whether they are related to symptoms of Chronic Multisymptom Illness (CMI). Methods Data from 224 post-9/11 veterans who self-reported exposure to hazards in theater were analyzed using hierarchical regression. Results Of the sample, 97.2% endorsed experiencing one or more potentially toxic exposure. In a regression model, toxic exposures and CMI symptoms were significantly associated above and beyond covariates. Follow-up analyses revealed that pesticide exposures, but not smoke inhalation was associated with CMI symptoms. Conclusions These findings suggest that toxic exposures were common among military personnel deployed to the most recent conflicts, and appear to be associated with CMI symptoms. Additional research on the impact of toxic exposures on returning Iraq and Afghanistan Veterans’ health is needed. PMID:28045798

Response surface model for predicting chronic toxicity of cadmium to Paronychiurus kimi (Collembola), with a special emphasis on the importance of soil characteristics in the reproduction test.

PubMed

Son, Jino; Shin, Key-il; Cho, Kijong

2009-11-01

A central composite design (CCD) was employed to investigate the effects of organic matter (OM) content and soil pH on the reproduction, and chronic toxicity (28-d EC(50-reproduction)) of cadmium for Paronychiurus kimi after 28days exposure in a standard artificial soil. Two statistical models were developed, one describing reproduction in control artificial soils as a function of OM content and pH, and the other describing cadmium toxicity to the same soil parameters. In the reproduction model, pH was the most important factor, followed by two quadratic factors of OM(2) and pH(2). The parameter pH alone could explain 75.5% of the response variation. The reproduction model will allow us to predict a mean reproduction in the non-treated control soils that contain various combinations of OM content and different pH values. In the chronic toxicity model, only the linear factor of the OM content and pH significantly (p<0.05) affect cadmium toxicity, which explains the 78.9% and 14.9% of total response variance, respectively. Therefore, the final polynomial regression describing the chronic toxicity of cadmium to P. kimi is as follows: predicted 28-d EC(50) of cadmium (mgkg(-1))=-21.231+2.794 x OM+4.874 x pH. The present study show that soil characteristics, which can alter the toxicity of cadmium, can also act as stressors themselves in regards to the reproduction of P. kimi. Based on the physico-chemical characteristics of the test media, the response surface model developed in this study can be used to provide initial toxicity information for cadmium within a region of interest in terms of OM content and pH, and may lead to more scientific based risk assessment for metals.

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.

USER GUIDE: ACUTE TO CHRONIC ESTIMATION

EPA Science Inventory

Acute and chronic toxicity testing plays a major role in ecological risk assessment requirements involved in several environmental laws. Chronic toxicity tests commonly include the measurement of long-term effects of a contaminant on the survival, growth, and reproduction of test...

[Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

PubMed

Aguirrebengoa, Koldo

2014-11-01

Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acute and chronic effects of heavy metals and cyanide on Mysidopsis bahia (crustacea:mysidacea)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lussier, S.M.; Gentile, J.H.; Walker, J.

1985-01-01

Acute and whole life-cycle toxicity tests were conducted with the estuarine mysid shrimp, Mysidopsis bahia, exposed to cyanide and selected heavy metals. Acute toxicity values (96h LC50) ranged from 3.5 micrograms/1 for mercury to 3130 micrograms/1 for lead, and were ranked in order of toxicity: (greatest)Hg, Cd, Cu, Cn, Ag, Sn, Ni, As, Cr, and Pb(least). The chronic toxicity values ranged from 1.2 micrograms/1 for mercury to 893 micrograms/1 for arsenic. Chronic values were calculated from either survival, time to first reproduction, or number of young produced. When acute toxicity data for the same chemical are compared, M. bahia ismore » consistently among the more sensitive marine species. Lack of comparable data precludes a similar observation with chronic tests. Examination of the relative sensitivity of the chronic responses indicates that only for cadmium was survival more sensitive than reproduction.« less

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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds

PubMed Central

Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A.V.

2012-01-01

Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption. PMID:27847445

Evaluation of water treatment sludges toxicity using the Daphnia bioassay.

PubMed

Sotero-Santos, Rosana B; Rocha, Odete; Povinelli, Jurandyr

2005-10-01

Alum and ferric chloride sludges from two water treatment plants (WTPs) were analyzed regarding their physicochemical characteristics and toxicity to Daphnia similis. Experiments were carried out in the dry and rainy seasons. Acute and chronic toxicity was measured using survival and reproduction as measurement endpoints. No acute toxicity of the sludge was observed in 48 h exposure. Ferric chloride sludge caused chronic toxicity, demonstrated by low fecundity and some mortality, while alum sludge caused chronic toxicity characterized by low fecundity. Some sludge characteristics varied between samplings, including turbidity, solids contents, N, P and metal (Al and Fe) concentrations. These variables and the increase of chemical oxygen demand (COD) were identified as the main cause of degradation of the receiving waters. However, no relationship was observed between these variables and degree of toxicity. It is apparent from these results that water treatment sludges may be toxic and therefore may impair receiving waters. Alum sludge was less toxic than ferric chloride sludge.

Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

PubMed

Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

2016-11-01

Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

NEUROCHEMICAL EFFECTS OF CHRONIC DIETARY AND REPEATED HIGH-LEVEL ACUTE EXPOSURE TO CHLORPYRIFOS IN RATS.

EPA Science Inventory

Lots of information is available surrounding the acute toxicity of anticholinesterase pesticides, but these have been very few detailed studies on the chronic effects of these pesticides. Humans are exposed on a chronic basis and some humans believe that have been affected advers...

The use of dogs as second species in regulatory testing of pesticides. Part II: Subacute, subchronic and chronic studies in the dog.

PubMed

Spielmann, H; Gerbracht, U

2001-03-01

Data on 172 pesticides (fungicides, herbicides, insecticides and other pesticides) submitted for regulatory purposes during the past 40 years to the German Federal Institute for the Health Protection of Consumers and Veterinary Medicine (BgVV) were analysed to determine whether chronic studies in dogs (52/104 weeks) provide essential additional specific toxicological compared with subchronic (13 weeks) or subacute (4 weeks) studies in the same species. Comparison of the lowest observed effect levels (LOELs) in dogs revealed no significant differences between subchronic and chronic studies but a significant difference between subacute studies and subchronic or chronic studies. Moreover, there was a significant correlation between the LOELs determined in subchronic studies and those determined in chronic studies in dogs (r = 0.78-0.84). The distribution of target organ toxicity determined in chronic studies in dogs was not significantly different from the distribution determined in subchronic studies, except for effects on the spleen in studies on herbicides which were only observed in chronic studies and in combined subchronic/chronic studies, but never in subchronic studies. Organ-specific effects that were observed in chronic studies but not in subchronic studies were found in 30 of 55 studies on fungicides, in 25 of 44 on herbicides, in 17 of 38 on insecticides and in 10 of 16 on other pesticides. Compared with 26-week studies, additional organ-specific toxic effects were found in three of five, in three of four, in one of three and in one of one 52/104-week studies on fungicides, of herbicides, of insecticides and other pesticides, respectively. The organ-specific effects that were seen only in the chronic dog studies were evaluated according to their severity, e.g. significant damage to organs versus changes in enzyme activities that do not affect organ function or histology. Such effects were not considered to be specific for dogs in chronic studies if similar effects were also found in chronic studies in rodents (rat or mouse). In 15 of 141 studies in dogs serious side effects were observed in chronic studies that were not observed in subchronic studies. Furthermore, for 9 of 172 pesticides significant new effects were seen in 52/104-week studies when compared with 4- or 13-week studies and in 7 of 141 52/104-week studies when compared with 13-week studies. Analysis of the severity of organ-specific toxic effects of pesticides revealed that chronic long-term studies (52/104 weeks) in dogs do not provide specific additional information to 26-week studies in the same species.

[Radiation therapy in patients with inflammatory bowel disease. A review].

PubMed

Jmour, Omar; Pellat, Anna; Colson-Durand, Laurianne; To, Nhu Hanh; Latorzeff, Igor; Sargos, Paul; Sobhani, Iradj; Belkacemi, Yazid

2018-05-01

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are multifactorial diseases characterized by a chronic intestinal inflammation. Abdominal and pelvic irradiation can result in acute or chronic digestive toxicity. A few old studies on small population samples have suggested an increase of gastro-intestinal toxicities in patients with IBD in case of irradiation. Nevertheless, the physiopathology is unknown. More recent studies, including new irradiation techniques, have shown less toxicity events in these patients with IBD. There are no recommendations for irradiation in patients with IBD. This review aims to report recent data on this topic and discuss them regarding radiation parameters. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

PubMed

Kudryasheva, N S; Rozhko, T V

2015-04-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

DTIC Science & Technology

2011-01-01

central nervous system, optic neuritis, chronic inflammatory demyelinating polyneuropathy ) 340, 341.0, 341.8, 341.9, 377.30, 377.31, 377.32, 377.34...neuropathy, polyneuropathy due to drugs or other toxic agents, critical illness polyneuropathy , other inflammatory and toxic neuropathy) 337.0, 337.9, 354.1...Popula- tions at high risk, such as those with chronic diseases, are sometimes not well represented in clinical studies; however, additional efforts

[Effect of lead on the cardiovascular system].

PubMed

Zyśko, Dorota; Chlebda, Ewa; Gajek, Jacek

2004-11-01

Lead is a metal widely spread in the natural environment. It is strongly toxic, particularly to the peripheral and central nervous systems. The toxic influence on the cardiovascular system is most pronounced in case of higher exposures, where myocardium and the renal circulation are affected, in consequence of which secondary arterial hypertension can develop. It seems that lead affects the cardiovascular system mainly by changing the peripheral autonomic nervous system and leading to chronic neuropathy. Chronic exposure, even to low doses of lead, can impair conduction in myocardium. In order to assess those changes thoroughly prospective studies involving newly employed workers with occupational exposure to toxic activity of lead will be necessary.

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

PubMed

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

2017-08-01

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

Hazard-Ranking of Agricultural Pesticides for Chronic Health Effects in Yuma County, Arizona

PubMed Central

Sugeng, Anastasia J.; Beamer, Paloma I.; Lutz, Eric A.; Rosales, Cecilia B.

2013-01-01

With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. PMID:23783270

Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats.

PubMed

Sireeratawong, Seewaboon; Jaijoy, Kanjana; Khonsung, Parirat; Lertprasertsuk, Nirush; Ingkaninan, Kornkanok

2016-07-27

Bacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters. Acute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy. The acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range. A single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.

Evaluation of ionic contribution to the toxicity of a coal-mine effluent using Ceriodaphnia dubia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kennedy, A.J.; Cherry, D.S.; Zipper, C.E.

2005-08-01

The United States Environmental Protection Agency has defined national in-stream water-quality criteria (WQC) for 157 pollutants. No WQC to protect aquatic life exist for total dissolved solids (TDS). Some water-treatment processes (e.g., pH modifications) discharge wastewaters of potentially adverse TDS into freshwater systems. Strong correlations between specific conductivity, a TDS surrogate, and several biotic indices in a previous study suggested that TDS caused by a coal-mine effluent was the primary stressor. Further acute and chronic testing in the current study with Ceriodaphnia dubia in laboratory-manipulated media indicated that the majority of the effluent toxicity could be attributed to the mostmore » abundant ions in the discharge, sodium (1952 mg/L) and/or sulfate (3672 mg/L), although the hardness of the effluent (792 43 mg/L as CaCO{sub 3}) ameliorated some toxicity. Based on laboratory testing of several effluent-mimicking media, sodium- and sulfate-dominated TDS was acutely toxic at approximately 7000 {mu} S/cm (5143 mg TDS/L), and chronic toxicity occurred at approximately 3200 {mu} S/cm (2331 mg TDS/L). At a lower hardness (88 mg/L as CaCO{sub 3}), acute and chronic toxicity end-points were decreased to approximately 5000 {mu} S/cm (3663 mg TDS/L) and approximately 2000 {mu} S/cm (1443 mg TDS/L), respectively. Point-source discharges causing in-stream TDS concentrations to exceed these levels may risk impairment to aquatic life.« less

Safety evaluation of a proprietary food-grade, dried fermentate preparation of Saccharomyces cerevisiae.

PubMed

Schauss, Alexander G; Glavits, R; Endres, John; Jensen, Gitte S; Clewell, Amy

2012-01-01

A safety evaluation was performed for EpiCor, a product produced by a proprietary fermentation process using Saccharomyces cerevisiae. Studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome P450 ([CYP] CYP1A2 and CYP3A4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. No evidence of genotoxicity or mitogenicity was seen in any of the in vitro or in vivo studies. The CYP assessment showed no interactions or inductions. No toxic clinical symptoms or histopathological lesions were observed in the acute, subchronic, or chronic oral toxicity studies in the rat. Results of the studies performed indicate that EpiCor does not possess genotoxic activity and has a low order of toxicity that is well tolerated when administered orally. The no observable adverse effect level (NOAEL) was 1500 mg/kg body weight (bw)/d for the 90-day study and 800 mg/kg bw/d for the 1 year study, for the highest doses tested.

Risk Assessment for Criteria Pollutants and Air Toxics in two Sites of Mexico City During 2003 Field Campaign

NASA Astrophysics Data System (ADS)

García, A. R.; Grutter, M. M.; Volkamer, R. M.

2007-05-01

An environmental risk assessment for criteria pollutants and air toxics in Mexico City is presented. The data used in the study were collected by FTIR and DOAS systems during the Mexico City Metropolitan Area field campaign on April 2003 (MCMA2003). The systems were deployed in two different sites: One in downtown (Merced) and the other in the south east (CENICA). Concentrations of criteria pollutants and air toxics were obtained every 5 min and were used to obtain hourly average concentrations and the month average for April. The concentration values were used to estimate the risks of acute and chronic exposure to ambient concentrations using risk measures like hazard index, life cancer probability, life lost expectancy and maximum individual cancer risk. Results revealed that both sites have similar risk values. For acute exposure, criteria pollutants have larger risks than air toxics, but air toxics have larger risks for chronic exposure. Ambient concentrations of benzene showed the largest carcinogenic risk of the measured air toxics.

Acute and chronic toxicity of nickel to rainbow trout (Oncorhynchus mykiss).

PubMed

Brix, Kevin V; Keithly, James; DeForest, David K; Laughlin, Jim

2004-09-01

Of the fish species tested in chronic Ni exposures, rainbow trout (Oncorhynchus mykiss) is the most sensitive. To develop additional Ni toxicity data and to investigate the toxic mode of action for Ni, we conducted acute (96-h) and chronic (85-d early life-stage) flow-through studies using rainbow trout. In addition to standard toxicological endpoints, we investigated the effects of Ni on ionoregulatory physiology (Na, Ca, and Mg). The acute median lethal concentration for Ni was 20.8 mg/L, and the 24-h gill median lethal accumulation was 666 nmol/g wet weight. No effects on plasma Ca, Mg, or Na were observed during acute exposure. In the chronic study, no significant effects on embryo survival, swim-up, hatching, or fingerling survival or growth were observed at dissolved Ni concentrations up to 466 microg/L, the highest concentration tested. This concentration is considerably higher than the only other reported chronic no-observed-effect concentration (<33 microg/L) for rainbow trout. Accumulation of Ni in trout eggs indicates the chorion is only a partial barrier with 36%, 63%, and 1% of total accumulated Ni associated with the chorion, yolk, and embryo, respectively. Whole-egg ion concentrations were reduced by Ni exposure. However, most of this reduction occurred in the chorion rather than in the embryos, and no effects on hatching success or larval survival were observed as a result. Plasma ion concentrations measured in swim-up fingerlings at the end of the chronic-exposure period were not significantly reduced by exposure to Ni. Nickel accumulated on the gill in an exponential manner but plateaued in trout plasma at waterborne Ni concentrations of 118 microg/L or greater. Consistent with previous studies, Ni did not appear to disrupt ionoregulation in acute exposures of rainbow trout. Our results also suggest that Ni is not an ionoregulatory toxicant in long-term exposures, but the lack of effects in the highest Ni treatment precludes a definitive conclusion.

Analysis of quantitative data obtained from toxicity studies showing non-normal distribution.

PubMed

Kobayashi, Katsumi

2005-05-01

The data obtained from toxicity studies are examined for homogeneity of variance, but, usually, they are not examined for normal distribution. In this study I examined the measured items of a carcinogenicity/chronic toxicity study with rats for both homogeneity of variance and normal distribution. It was observed that a lot of hematology and biochemistry items showed non-normal distribution. For testing normal distribution of the data obtained from toxicity studies, the data of the concurrent control group may be examined, and for the data that show a non-normal distribution, non-parametric tests with robustness may be applied.

Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.

1995-12-31

The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size ofmore » the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.« less

Environmental Determinants of Chronic Disease and Medical Approaches: Recognition, Avoidance, Supportive Therapy, and Detoxification

PubMed Central

Sears, Margaret E.; Genuis, Stephen J.

2012-01-01

The World Health Organization warns that chronic, noncommunicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neurocognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bioaccumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives—biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Healthcare practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity. PMID:22315626

Aquatic toxicity of petroleum products and dispersant agents ...

EPA Pesticide Factsheets

The U.S. EPA Office of Research and Development has developed baseline data on the ecotoxicity of selected petroleum products and several chemical dispersants as part of its oil spills research program. Two diluted bitumens (dilbits) from the Alberta Tar Sands were tested for acute and chronic toxicity to standard freshwater and marine organisms given their spill potential during shipment within the United States. Separately, two reference crude oils representing a range of characteristics, and their mixtures with four representative dispersants, were tested to evaluate acute and chronic toxicity to marine organisms in support of Subpart J of the U.S. National Contingency Plan. Water accommodated fractions (WAF) of oil were prepared using traditional slow-stir methods and toxicity tests generally followed U.S. EPA standard effluent testing guidelines. WAFs were characterized for petroleum hydrocarbons including alkyl PAH homologs. The results of these studies will assist the U.S. EPA to assess toxicity data for unconventional oils (dilbits), and establish baseline toxicity data for selected crude oils and dispersant in support of planning and response activities. Abstract reporting the results of EPA's oil and dispersant toxicity testing program

Hypercalcaemia secondary to hypervitaminosis a in a patient with chronic renal failure.

PubMed

Hammoud, D; El Haddad, B; Abdallah, J

2014-01-01

Vitamin A toxicity is a well-described medical condition with a multitude of potential presenting signs and symptoms. It can be divided into acute and chronic toxicity. Serum vitamin A concentrations are raised in chronic renal failure even with ingestion of less than the usual toxic doses. Hypercalcaemia can occasionally be associated with high levels of vitamin A but it is rare. In this report, we describe a 67- year old female patient with chronic kidney disease who was taking vitamin A supplements for approximately 10 years. The patient had worsening of her chronic kidney disease over the last years and developed chronic hypercalcaemia. Her vitamin A level was elevated with a daily intake of 7000 IU. The vitamin A supplement was stopped. A few months later, vitamin A level diminished substantially and serum calcium levels returned to normal.

Toxic Hazards Research Unit annual technical report, 1972

NASA Technical Reports Server (NTRS)

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

1972-01-01

The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1971 through May 1972 are reviewed in this report. Acute inhalation toxicity experiments were conducted on hydrogen chloride (HCl) gas and aerosol, ethyl bromide (C2H5Br), hydrogen bromide (HBr), hydrogen sulfide (H2S), ammonia (NH3), chlorine (CL2), and silane (SiH4). Subacute toxicity studies were conducted on chlorine pentafluoride (ClF5), dichloromethane (CH2Cl2) and coal tar volatiles. Further toxicity studies of subacute and chronic responses to inhaled monomethylhydrazine (MMH) are also described.

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2011 CFR

2011-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2013 CFR

2013-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2012 CFR

2012-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2014 CFR

2014-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

Long-term trends in the intensity and relative toxicity of herbicide use

NASA Astrophysics Data System (ADS)

Kniss, Andrew R.

2017-04-01

Herbicide use is among the most criticized aspects of modern farming, especially as it relates to genetically engineered (GE) crops. Many previous analyses have used flawed metrics to evaluate herbicide intensity and toxicity trends. Here, I show that herbicide use intensity increased over the last 25 years in maize, cotton, rice and wheat. Although GE crops have been previously implicated in increasing herbicide use, herbicide increases were more rapid in non-GE crops. Even as herbicide use increased, chronic toxicity associated with herbicide use decreased in two out of six crops, while acute toxicity decreased in four out of six crops. In the final year for which data were available (2014 or 2015), glyphosate accounted for 26% of maize, 43% of soybean and 45% of cotton herbicide applications. However, due to relatively low chronic toxicity, glyphosate contributed only 0.1, 0.3 and 3.5% of the chronic toxicity hazard in those crops, respectively.

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...

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...

Development of predicted no effect concentration (PNEC) for TCS to terrestrial species.

PubMed

Wang, Xiaonan; Zhang, Cong; Liu, Zhengtao; Wang, Wanhua; Chen, Lihong

2015-11-01

Triclosan (TCS) is an important broad-spectrum antimicrobial agent widely utilized in a range of personal care products, and is therefore commonly found in the environment. A few studies have been conducted to investigate predicted no effect concentration (PNEC) for TCS on terrestrial organisms. This could be due to lack of toxicity data especially chronic toxicity data for species on various taxonomic levels. In the present study, chronic toxicity of TCS on 6 terrestrial species (3 dicotyledonous plants, 2 monocotyledonous plants and 1 terrestrial invertebrate) were tested. PNEC values of TCS based on toxicity data of 14 terrestrial species (5 dicotyledonous plants, 4 monocotyledonous plants and 5 terrestrial invertebrates) from 4 Phyla and 11 Families were calculated using the log-logistic species sensitivity distribution (SSD) method. The result of our toxicity tests showed that the dicotyledonous plant Lactuca sativa was the most sensitive species to TCS exposure. The PNEC value for TCS was derived to be 0.04-0.21mgkg(-1) when using the log-logistic SSD method. The use of toxicity data from various taxonomic levels is recommended in deriving the PNEC value in the terrestrial environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ecological risk assessment of bisphenol A in surface waters of China based on both traditional and reproductive endpoints.

PubMed

Guo, Lei; Li, Zhengyan; Gao, Pei; Hu, Hong; Gibson, Mark

2015-11-01

Bisphenol A (BPA) occurs widely in natural waters with both traditional and reproductive toxicity to various aquatic species. The water quality criteria (WQC), however, have not been established in China, which hinders the ecological risk assessment for the pollutant. This study therefore aims to derive the water quality criteria for BPA based on both acute and chronic toxicity endpoints and to assess the ecological risk in surface waters of China. A total of 15 acute toxicity values tested with aquatic species resident in China were found in published literature, which were simulated with the species sensitivity distribution (SSD) model for the derivation of criterion maximum concentration (CMC). 18 chronic toxicity values with traditional endpoints were simulated for the derivation of traditional criterion continuous concentration (CCC) and 12 chronic toxicity values with reproductive endpoints were for reproductive CCC. Based on the derived WQC, the ecological risk of BPA in surface waters of China was assessed with risk quotient (RQ) method. The results showed that the CMC, traditional CCC and reproductive CCC were 1518μgL(-1), 2.19μgL(-1) and 0.86μgL(-1), respectively. The acute risk of BPA was negligible with RQ values much lower than 0.1. The chronic risk was however much higher with RQ values of between 0.01-3.76 and 0.03-9.57 based on traditional and reproductive CCC, respectively. The chronic RQ values on reproductive endpoints were about threefold as high as those on traditional endpoints, indicating that ecological risk assessment based on traditional effects may not guarantee the safety of aquatic biota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

PubMed

Shankar, Priyanka; Ghosh, Sudip; Bhaskarachary, K; Venkaiah, K; Khandare, Arjun L

2013-07-14

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

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.

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

PubMed

Tang, Rong; Tian, Ru-Hua; Cai, Jia-Zhong; Wu, Jun-Hui; Shen, Xiao-Ling; Hu, Ying-Jie

2017-12-01

The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. This study examines the toxicological profiles of C. cajan leaf extracts. The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

Cumulative influences of a small city and former mining activities on the sediment quality of a subtropical estuarine protected area.

PubMed

Cruz, Ana Carolina Feitosa; Davanso, Marcela Bergo; Araujo, Giuliana Seraphim; Buruaem, Lucas M; Santaella, Sandra Tédde; de Morais, Rodofley Davino; Abessa, Denis M S

2014-11-01

This study aimed to evaluate the sediment quality in the estuarine protected area known as Cananéia-Iguape-Peruíbe (CIP-PA), located on the southeastern coast of Brazil. The study was designed considering possible negative effects induced by the city of Cananéia on the sediment quality of surrounding areas. This evaluation was performed using chemical and ecotoxicological analyses. Sediments were predominantly sandy, with low CaCO3 contents. Amounts of organic matter varied, but higher contents occurred closer to the city, as well as did Fe and Total Recoverable Oils and Greases (TROGs) concentrations. Contamination by Cd and Cu was revealed in some samples, while concentrations of Zn were considered low. Chronic toxicity was detected in all tested sediments and acute toxicity occurred only in sediments collected near the city. The principal component analysis (PCA) revealed an association among Cd, Cu, Fe, TROG, fines, organic matter, CaCO3, and chronic toxicity, whereas acute toxicity was found to be associated with Zn and mud. However, because Zn levels were low, acute toxicity was likely due to a contaminant that was not measured. Results show that there is a broad area within the CIP-PA that is under the influence of mining activities (chronic toxicity, moderate contamination by metals), whereas poorer conditions occur closer to Cananéia (acute toxicity); thus, the urban area seems to constitute a relevant source of contaminants for the estuarine complex. These results show that contamination is already capable of producing risks for the local aquatic biota, which suggests that the CIP-PA effectiveness in protecting estuarine biota may be threatened.

Hazard-ranking of agricultural pesticides for chronic health effects in Yuma County, Arizona.

PubMed

Sugeng, Anastasia J; Beamer, Paloma I; Lutz, Eric A; Rosales, Cecilia B

2013-10-01

With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam-sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. Copyright © 2013 Elsevier B.V. All rights reserved.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.« less

78 FR 78731 - Indoxacarb; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

.../kg/day Chronic RfD = 0.02 Weight of evidence approach was UFA = 10x mg/kg/day. used from four studies..... Weight of evidence approach was 30 days), intermediate-term (1 UFA = 10x used from four studies: to 6..., one developmental toxicity study in rats with DPX-MP062 and DPX-KN128, one developmental toxicity...

Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

PubMed

Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-01-01

Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures.

PubMed

Kunz, James L; Ingersoll, Chris G; Smalling, Kelly L; Elskus, Adria A; Kuivila, Kathryn M

2017-09-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubia and L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. azteca reproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;36:2308-2315. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 SETAC.

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.

An ecological risk assessment of the acute and chronic effects of the herbicide clopyralid to rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

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

2009-01-01

Clopyralid (3,6-dichloro-2-pyridinecarboxylic acid) is a pyridine herbicide frequently used to control invasive, noxious weeds in the northwestern United States. Clopyralid exhibits low acute toxicity to fish, including the rainbow trout (Oncorhynchus mykiss) and the threatened bull trout (Salvelinus confluentus). However, there are no published chronic toxicity data for clopyralid and fish that can be used in ecological risk assessments. We conducted 30-day chronic toxicity studies with juvenile rainbow trout exposed to the acid form of clopyralid. The 30-day maximum acceptable toxicant concentration (MATC) for growth, calculated as the geometric mean of the no observable effect concentration (68 mg/L) and the lowest observable effect concentration (136 mg/L), was 96 mg/L. No mortality was measured at the highest chronic concentration tested (273 mg/L). The acute:chronic ratio, calculated by dividing the previously published 96-h acutely lethal concentration (96-h ALC50; 700 mg/L) by the MATC was 7.3. Toxicity values were compared to a four-tiered exposure assessment profile assuming an application rate of 1.12 kg/ha. The Tier 1 exposure estimation, based on direct overspray of a 2-m deep pond, was 0.055 mg/L. The Tier 2 maximum exposure estimate, based on the Generic Exposure Estimate Concentration model (GEENEC), was 0.057 mg/L. The Tier 3 maximum exposure estimate, based on previously published results of the Groundwater Loading Effects of Agricultural Management Systems model (GLEAMS), was 0.073 mg/L. The Tier 4 exposure estimate, based on published edge-of-field monitoring data, was estimated at 0.008 mg/L. Comparison of toxicity data to estimated environmental concentrations of clopyralid indicates that the safety factor for rainbow trout exposed to clopyralid at labeled use rates exceeds 1000. Therefore, the herbicide presents little to no risk to rainbow trout or other salmonids such as the threatened bull trout. ?? 2009 US Government.

Use of lung toxicity and lung particle clearance to estimate the maximum tolerated dose (MTD) for a fiber glass chronic inhalation study in the rat.

PubMed

Hesterberg, T W; McConnel, E E; Miiller, W C; Chevalier, J; Everitt, J; Thevenaz, P; Fleissner, H; Oberdörster, G

1996-07-01

Short-term toxicity and lung clearance were assessed in rats exposed by inhalation to size-selected fibrous glass (FG) for 13 weeks. Results from this study and from a recent FG chronic inhalation study are presented here as guidelines for the selection of a maximum tolerated dose (MTD) for chronic inhalation studies of fibers. Fischer 344 rats were exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 13 weeks to one of five concentrations of FG (36, 206, 316, 552, or 714 fibers/cc; expressed gravimetrically, 3, 16, 30, 45, or 60 mg/m3) or to filtered air. Rats were then held for an additional 10 weeks of postexposure recovery. Test fiber was size-selected from glass wool having a chemical composition representative of building insulation. Rats were terminated at 7, 13, 19, and 23 weeks after the onset of exposure to evaluate pulmonary pathology, lung epithelium cell proliferation, lung fiber burden, and lung lavage cells and chemistry. The effect of fiber inhalation on lung clearance of innocuous microspheres was also evaluated: following fiber exposure, six rats/group were exposed to 85Sr-labeled 3.0-microns polystyrene microspheres by intratracheal inhalation and then monitored for whole-body radioactivity during the 10-week recovery period. Data from the short-term study support the choice of 30 mg/m3 as the MTD for the previous chronic FG study and also provide indicators of long-term lung toxicity and functional impairment that can be used to estimate the MTD for future chronic fiber inhalation studies.

Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

PubMed

Verheijen, Marcha; Schrooders, Yannick; Gmuender, Hans; Nudischer, Ramona; Clayton, Olivia; Hynes, James; Niederer, Steven; Cordes, Henrik; Kuepfer, Lars; Kleinjans, Jos; Caiment, Florian

2018-05-24

Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death. We present an in vitro experimental design aimed at detecting DOX-induced cardiotoxicity by obtaining a global view of the induced molecular mechanisms through RNA-sequencing. To better reflect the in vivo situation, human 3D cardiac microtissues were exposed to physiologically-based pharmacokinetic (PBPK) relevant doses of DOX for 2 weeks. We analysed a therapeutic and a toxic dosing profile. Transcriptomics analysis revealed significant gene expression changes in pathways related to "striated muscle contraction" and "respiratory electron transport", thus suggesting mitochondrial dysfunction as an underlying mechanism for cardiotoxicity. Furthermore, expression changes in mitochondrial processes differed significantly between the doses. Therapeutic dose reflects processes resembling the phenotype of delayed chronic cardiotoxicity, while toxic doses resembled acute cardiotoxicity. Overall, these results demonstrate the capability of our innovative in vitro approach to detect the three known mechanisms of DOX leading to toxicity, thus suggesting its potential relevance for reflecting the patient situation. Our study also demonstrated the importance of applying physiologically relevant doses during toxicological research, since mechanisms of acute and chronic toxicity differ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Hypercalcaemia Secondary to Hypervitaminosis A in a Patient with Chronic Renal Failure

PubMed Central

Hammoud, D; El Haddad, B; Abdallah, J

2014-01-01

Vitamin A toxicity is a well-described medical condition with a multitude of potential presenting signs and symptoms. It can be divided into acute and chronic toxicity. Serum vitamin A concentrations are raised in chronic renal failure even with ingestion of less than the usual toxic doses. Hypercalcaemia can occasionally be associated with high levels of vitamin A but it is rare. In this report, we describe a 67- year old female patient with chronic kidney disease who was taking vitamin A supplements for approximately 10 years. The patient had worsening of her chronic kidney disease over the last years and developed chronic hypercalcaemia. Her vitamin A level was elevated with a daily intake of 7000 IU. The vitamin A supplement was stopped. A few months later, vitamin A level diminished substantially and serum calcium levels returned to normal. PMID:25303202

[Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

PubMed

Lebedev, S P

1982-01-01

Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

Assessing Toxicity of Obscurant Grade Pan-Based Carbon Fiber Aquatic Species Chronic Tests

DTIC Science & Technology

2004-12-01

ASSESSING TOXICITY OF OBSCURANT GRADE PAN-BASED CARBON FIBER: AQUATIC SPECIES CHRONIC TESTS N. A. Chester, M. V. Haley, C. W. Kurnas and R. T...with minimal restrictions. To this end we are investigating the toxicity of PAN-based carbon fibers to the aquatic species Ceriodaphnia dubia (water... toxicity methods to provide ecotoxicological results for both lethal and sub-lethal parameters, including LC50 (24-, 48- and 96-h), IC50, EC20, and

Comparative assessment of toxicity of ZnO and amine-functionalized ZnO nanorods toward Daphnia magna in acute and chronic multigenerational tests.

PubMed

Gonçalves, Renata Amanda; de Oliveira Franco Rossetto, Ana Letícia; Nogueira, Diego José; Vicentini, Denice Schulz; Matias, William Gerson

2018-04-01

Zinc oxide nanomaterials (ZnO NM) have been used in a large number of applications due to their interesting physicochemical properties. However, the increasing use of ZnO NM has led to concerns regarding their environmental impacts. In this study, the acute and chronic toxicity of ZnO nanorods (NR) bare (ZnONR) and amine-functionalized (ZnONR@AF) toward the freshwater microcrustacean Daphnia magna was evaluated. The ZnO NR were characterized by transmission electron microscopy (TEM), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and the zeta potential and hydrodynamic diameter (HD). The acute EC50 (48h) values for D. magna revealed that the ZnONR@AF were more toxic than the ZnONR. The generation of reactive oxygen species (ROS) was observed in both NM. Regarding the chronic toxicity, the ZnONR@AF were again found to be more toxic than the ZnONR toward D. magna. An effect on longevity was observed for ZnONR, while ZnONR@AF affected the reproduction, growth and longevity. In the multigenerational recovery test, we observed that maternal exposure can affect the offspring even when these organisms are not directly exposed to the ZnO NR. Copyright © 2018 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herkovits, J.; Herkovits, F.D.; Perez-Coll, C.S.

The water quality based toxics control is essential to evaluate the aggregate toxicity, bioavailability as well as for the detection and/or prediction of ecological impacts. Reconquista River valley is situated in the north area of Great Buenos Aires with a population of three million inhabitants. The river is loaded with industrial and municipal waste water. In the present preliminary study the authors report the toxicity found in surface water at a 6 sample stations (including a reference point and a stream) all of them downstream from mixing zone areas. The ecotoxicological study was performed with three native species (Bufo arenarummore » embryos, Cnesterodon decemmaculatus and a species of shrimp collected in an upstream reference site) during a 7 day renewal toxicity test conducted with 10 individuals (by duplicate) for each condition plus control. The results point out that the Bufo arenarum embryos test is the most sensitive to toxic substances as well as the better adapted species to the changing physico-chemical conditions of this river. The results obtained with embryos, expressed in Acute and Chronic Toxicity Units (according USEPA) range between <0.3--2 and <1--5 respectively (recommended magnitudes for industrial effluents according USEPA: 0.3 and 1 toxicity units respectively). Therefore, the toxicity found in Reconquista River ecosystem was up to 6 times higher than the maximal value recommended for industrial effluents. It is noteworthy that in the place where toxicity starts to rise, a large number of dead fishes were found and from that place downstream, no macroorganisms were found in the river. The results confirm the high sensitivity of Bufo arenarum embryos for continental waters ecotoxicological studies and the possibility of using this test as a short-term chronic toxicity method for water quality-based toxics control.« less

The acute and chronic toxicity of major geochemical ions to Hyalella azteca Ion interactions and comparisons to other species

EPA Science Inventory

We have previously reported that the acute and chronic toxicities of major geochemical ions (Na, K, Ca, Mg, Cl, SO4, HCO3) to Ceriodaphnia dubia can involve multiple, independent mechanisms. The toxicities of K, Mg, and Ca salts were best related to the chemical activity of the c...

Aflatoxins--experimental studies.

PubMed

Tulpule, P G

1981-01-01

The susceptibility of animals to both chronic and acute aflatoxicosis is variable between species and depends upon not only the dose of the toxin and the duration of exposure but also upon the age, sex, and nutritional status of the animal. In general, acute toxicity is manifested by necrosis and cirrhosis, and chronic toxicity by carcinoma of the liver. Current research using both in vivo and in vitro studies has shown that the differences in response to aflatoxin in different animals can be attributed to their differential metabolism. The rates of metabolism and intermediate products formed are important factors in determining the type of toxic action of aflatoxin B1. According to these criteria, monkey and man are more susceptible to acute aflatoxicosis and relatively resistant to carcinogenic effects. On the other hand, animals, such as sheep and rat, are more susceptible to carcinogenic effects.

Development of a strontium chronic effects benchmark for aquatic life in freshwater.

PubMed

McPherson, Cathy A; Lawrence, Gary S; Elphick, James R; Chapman, Peter M

2014-11-01

There are no national water-quality guidelines for strontium for the protection of freshwater aquatic life in North America or elsewhere. Available data on the acute and chronic toxicity of strontium to freshwater aquatic life were compiled and reviewed. Acute toxicity was reported to occur at concentrations ranging from 75 mg/L to 15 000 mg/L. The majority of chronic effects occurred at concentrations above 11 mg/L; however, calculation of a representative benchmark was confounded by results from 4 studies indicating that chronic effects occurred at lower concentrations than all other studies, in 2 cases below background concentrations reported for US and European streams. Two of these studies, including 1 reporting effects below background concentrations, were repeated and found not to be reproducible; chronic effects occurred at considerably higher strontium concentrations than in the original studies. Studies with narrow-mouthed toad and goldfish were not repeated; both studies reported chronic effects below background concentrations, and both studies had been conducted by the authors of 1 of the 2 studies that were repeated and shown to be nonreproducible. Studies by these authors (3 of the 4 confounding studies), conducted over 30 yr ago, lacked detail in reporting of methods and results. It is thus likely that repeating the toad and goldfish studies would also have resulted in a higher strontium effects concentration. A strontium chronic effects benchmark of 10.7 mg/L that incorporates the results of additional testing summarized in the present study is proposed for freshwater environments. © 2014 SETAC.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

PubMed

Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

2013-06-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

PubMed Central

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

Petroleum hydrocarbon toxicity to corals: A review.

PubMed

Turner, Nicholas R; Renegar, D Abigail

2017-06-30

The proximity of coral reefs to coastal urban areas and shipping lanes predisposes corals to petroleum pollution from multiple sources. Previous research has evaluated petroleum toxicity to coral using a variety of methodology, including monitoring effects of acute and chronic spills, in situ exposures, and ex situ exposures with both adult and larval stage corals. Variability in toxicant, bioassay conditions, species and other methodological disparities between studies prevents comprehensive conclusions regarding the toxicity of hydrocarbons to corals. Following standardized protocols and quantifying the concentration and composition of toxicant will aid in comparison of results between studies and extrapolation to actual spills. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

USGS Publications Warehouse

Ingersoll, Christopher G.; Contributions by Wang, Ning; Calfee, Robin D.; Beahan, Erinn; Brumbaugh, William G.; Dorman, Rebecca A.; Hardesty, Doug K.; Kunz, James L.; Little, Edward E.; Mebane, Christopher A.; Puglis, Holly J.

2014-01-01

White sturgeon (Acipenser transmontanus) are experiencing poor recruitment in the trans boundary reach of the upper Columbia River in eastern Washington State. Limited toxicity data indicated that early life stages of white sturgeon are sensitive to metals. In acute 4-day (d) exposures with larval white sturgeon, previous studies have reported that the 4-day median lethal concentrations (LC50) based on biotic ligand model (BLM) normalization for copper were below the U.S. Environmental Protection Agency national recommended acute water-quality criterion. In previously published chronic 66-d exposures starting with newly fertilized eggs of white sturgeon, 20-percent lethal effect concentrations (LC20s) for copper, cadmium, or zinc generally were within a factor of two of the chronic values of the most sensitive fish species in the databases of the U.S. Environmental Protection Agency water-quality criteria (WQC) for the three metals. However, there were some uncertainties in the chronic exposures previously performed with white sturgeon, including (1) low control survival (37 percent), (2) more control fish tested in each replicate compared to other treatments, (3) limited replication of treatments (n=2), (4) lack of reported growth data (such as dry weight), and (5) wide dilution factors for exposure concentrations (6- to 8-fold dilutions). The U.S. Environmental Protection Agency concluded that additional studies are needed to generate more toxicity data to better define lethal and sublethal toxicity thresholds for metals for white sturgeon. The objective of the study was to further evaluate the acute and chronic toxicity of cadmium, copper, lead, or zinc to early life stages of white sturgeon in water-only exposures. Toxicity tests also were performed with commonly tested rainbow trout (Oncorhynchus mykiss) under similar test conditions to determine the relative sensitivity between white sturgeon and rainbow trout to these metals. Toxicity data generated from this study were used to evaluate the sensitivity of early life stages of white sturgeon and rainbow trout relative to data published for other test organisms. Toxicity data generated from this study also were used to evaluate the level of protection of U.S. Environmental Protection Agency WQC or Washington State water-quality standards (WQS) for copper, zinc, cadmium, or lead to white sturgeon inhabiting the upper Columbia River. Chapter A of this report summarizes the results of acute toxicity tests performed for 4 d with white sturgeon and rainbow trout exposed to copper, cadmium, or zinc. Chapter B of this report summarizes the results of chronic toxicity tests performed for as many as 53 days with white sturgeon or rainbow trout exposed to copper, cadmium, zinc, or lead. Appendixes to the report are available at http://pubs.usgs.gov/sir/2013/5204. Supporting documentation for chapter A toxicity testing is provided in appendix 1. Supporting documentation for chapter B toxicity testing is provided in Appendix 2. Supporting documentation on analysis of water chemistry for chapter A and chapter B is provided in appendix 3 and 4. The rationale for applying corrections to measured copper and zinc values in water samples from some of the toxicity tests performed in chapter A is provided in appendix 5. A summary of dissolved organic carbon measurement variability and implications for biotic ligand model normalization for toxicity data summarized in chapter A and chapter B are provided in appendix 6. An evaluation of an interlaboratory comparison of analyses for dissolved organic carbon in water from the U.S. Geological Survey Columbia Environmental Research Center and University of Saskatchewan is provided in appendix 7. Finally, appendix 8 provides a summary of retesting of white sturgeon in 2012 to determine if improved survival of sturgeon would affect copper effect concentrations in 24-d copper exposures started with newly hatched larvae, and to evaluate the effect of light intensity or temperature on the response of newly hatched larvae during a 25-d study.

Toxicity decrease in urban wastewaters treated by a new biofiltration process.

PubMed

Binelli, A; Magni, S; Della Torre, C; Parolini, M

2015-12-15

We carried out a project aimed to evaluate the possible role played by the freshwater zebra mussel (Dreissena polymorpha) in the possible decrease of some environmental pollutants recalcitrant to tradition wastewater treatments. By the help of a pilot-plant built in the largest wastewater treatment plant of Milan (Italy), we tested several waste mixtures in order to measure the chemicals' abatement made by mussels' biofiltration. This study represents the last step of the wider project and it aimed to evaluate if the decrease in the concentration of some urban pollutants measured in wastewaters was followed by a corresponding toxicity reduction. Thus, we performed 7-day exposures under laboratory conditions to test the toxicity of the raw wastewaters and those preliminary filtered by zebra mussels, through the measurement of different end-points of acute and chronic toxicity. Results showed a clear positive effect of mussels' biofiltration mainly to decrease the acute toxicity made by the two tested wastewater mixtures, while the biomarkers' suite used to evaluate the chronic toxicity showed contradictory results. Copyright © 2015 Elsevier B.V. All rights reserved.

[Cognitive impairment in a toxic lesion of the brain].

PubMed

Katamanova, E V; Rukavishnikov, V S; Lakhman, O L; Shevchenko, O I; Denisova, I A

2015-01-01

To identify features of cognitive impairment in patients with toxic (mercury or alcohol) encephalopathy. The study involved 36 patients with chronic mercury intoxication and 30 people with chronic alcoholism. A control group included 30 age-matched healthy men who were not exposed to toxic substances and alcohol abuse. All patients underwent neuropsychological examination, which involved a set of neuropsychological Luria rated memory status, praxis, gnosis and speeches. MMSE and FAB were used for the diagnosis of moderate cognitive impairment. Computer electroencephalography and cognitive evoked potentials method were used as well. The diffuse brain injury in toxic encephalopathy (alcohol and mercury) on EEG, and according to the results of neuropsychological testing was identified. Changes in analytical and synthetic thinking, audio-verbal, long-term, visual memory, reciprocal coordination, finger gnosis, impressive speech were observed in mercury encephalopathy. Functional failure of the frontal lobe and the premotor area of the left hemisphere were revealed in alcoholic encephalopathy.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 ofmore » 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).« less

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

USGS Publications Warehouse

Wang, Ning; Ivey, Chris D.; Brunson, Eric L.; Cleveland, Danielle; Ingersoll, Christopher G.; Stubblefield, William A.; Cardwell, Allison S.

2018-01-01

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96‐h and chronic 28‐d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3. The acute 50% effect concentration (EC50) for survival of both species was >6200 μg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to <6.5 and hardness normalized to 100 mg/L, indicating that the mussel and amphipod were insensitive to Al in acute exposures. The chronic 20% effect concentration (EC20) based on dry weight was 163 μg total Al/L for the mussel and 409 μg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to <6.5 would rank the mussel (L. siliquoidea) as the fourth most sensitive species and the amphipod (H. azteca) as the fifth most sensitive species, indicating the 2 species were sensitive to Al in chronic exposures. The USEPA‐proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. 

CHLOROACETONITRILE (CAN) INDUCES GLUTATHIONE DEPLETION AND 8-HYDROXYLATION OF GUANINE BASES IN RAT GASTRIC MUCOSA. (R825955)

EPA Science Inventory

Chloroacetonitrile (CAN) is detected in drinking-water supplies as a by-product of the chlorination process. Gastroesophageal tissues are potential target sites of acute and chronic toxicity by haloacetonitriles (HAN). To examine the mechanism of CAN toxicity, we studied its effe...

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...

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.

Is the chronic Tier-1 effect assessment approach for insecticides protective for aquatic ecosystems?

PubMed

Brock, Theo Cm; Bhatta, Ranjana; van Wijngaarden, René Pa; Rico, Andreu

2016-10-01

We investigated the appropriateness of several methods, including those recommended in the Aquatic Guidance Document of the European Food Safety Authority (EFSA), for the derivation of chronic Tier-1 regulatory acceptable concentrations (RACs) for insecticides and aquatic organisms. The insecticides represented different chemical classes (organophosphates, pyrethroids, benzoylureas, insect growth regulators, biopesticides, carbamates, neonicotinoids, and miscellaneous). Chronic Tier-1 RACs derived using toxicity data for the standard species Daphnia magna, Chironomus spp., and/or Americamysis bahia, were compared with Tier-3 RACs derived from micro- and mesocosm studies on basis of the ecological threshold option (ETO-RACs). ETO-RACs could be derived for 31 insecticides applied to micro- and mesocosms in single or multiple applications, yielding a total number of 36 cases for comparison. The chronic Tier-1 RACs calculated according to the EFSA approach resulted in a sufficient protection level, except for 1 neonicotinoid (slightly underprotective) and for several pyrethroids if toxicity data for A. bahia were not included. This latter observation can be explained by 1) the fact that A. bahia is the most sensitive standard test species for pyrethroids, 2) the hydrophobic properties of pyrethroids, and 3) the fact that long-term effects observed in (epi) benthic arthropods may be better explained by exposure via the sediment than via overlying water. Besides including toxicity data for A. bahia, the protection level for pyrethroids can be improved by selecting both D. magna and Chironomus spp. as standard test species for chronic Tier-1 derivation. Although protective in the majority of cases, the conservativeness of the recommended chronic Tier-1 RACs appears to be less than an order of magnitude for a relatively large proportion of insecticides when compared with their Tier-3 ETO-RACs. This may leave limited options for refinement of the chronic effect assessment using laboratory toxicity data for additional species. Integr Environ Assess Manag 2016;12:747-758. © 2015 SETAC. © 2015 SETAC.

Problem Definition Study: Lead Beta-Resorcylate

DTIC Science & Technology

1979-02-01

unless so desig- nated by other authorized documents. -3- »SUMMARY Lead ß-resorcylate is used as a burning rate modifier in solid propel- lant... sediment and biota 3. Acute mammalian toxicity study 4. Chronic mammalian toxicity study 5. Determine the effectiveness of proposed treatment...burning rate moderator in solvent and solventless double base propellents. This salt enters the environment in the wastewater generated during the

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

PubMed

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye, Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-07-01

To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results. Copyright © 2012 Elsevier Inc. All rights reserved.

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghilezan, Michel, E-mail: mghilezan@beaumont.edu; Martinez, Alvaro; Gustason, Gary

2012-07-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, onlymore » 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results.« less

Chronic aflatoxin exposure in children living in Bhaktapur, Nepal: Extension of the MAL-ED study

USDA-ARS?s Scientific Manuscript database

Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are toxic chemicals produced by molds. The molds that produce these two toxic chemicals are commonly found in corn and their co-occurence in corn has been demonstrated in many surveys. This study was conducted because it is suspected that exposure to eith...

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.

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

EPA Science Inventory

Abstract for presentation

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

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

Ecotoxicity of naproxen and its phototransformation products.

PubMed

Isidori, Marina; Lavorgna, Margherita; Nardelli, Angela; Parrella, Alfredo; Previtera, Lucio; Rubino, Maria

2005-09-15

The occurrence of pharmaceuticals in the environment is of great concern and only few data are available about the adverse effects of such molecules and their derivatives on non-target aquatic organisms. This study was designed to assess the toxic potential of Naproxen, a nonsteroidal anti-inflammatory, Naproxen Na, its freely water soluble sodium salt and their photoproducts in the aquatic environment. Bioassays were performed on algae, rotifers and microcrustaceans to assess acute and chronic toxicity. Furthermore, possible genotoxic effects of photoderivatives were investigated using SOS chromotest and Ames fluctuation test. The results showed that photoproducts were more toxic than the parent compounds both for acute and chronic values, while genotoxic and mutagenic effects were not found. These findings suggested the opportunity to consider derivatives in ecotoxicology assessment of drugs.

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.

Derivation of occupational exposure levels (OELs) of low-toxicity isometric biopersistent particles: How can the kinetic lung overload paradigm be used for improved inhalation toxicity study design and OEL-derivation?

PubMed

Pauluhn, Jürgen

2014-12-20

Convincing evidence suggests that poorly soluble low-toxicity particles (PSP) exert two unifying major modes of action (MoA), in which one appears to be deposition-related acute, whilst the other is retention-related and occurs with particle accumulation in the lung and associated persistent inflammation. Either MoA has its study- and cumulative dose-specific adverse outcome and metric. Modeling procedures were applied to better understand as to which extent protocol variables may predetermine any specific outcome of study. The results from modeled and empirical studies served as basis to derive OELs from modeled and empirically confirmed directions. This analysis demonstrates that the accumulated retained particle displacement volume was the most prominent unifying denominator linking the pulmonary retained volumetric particle dose to inflammogenicity and toxicity. However, conventional study design may not always be appropriate to unequivocally discriminate the surface thermodynamics-related acute adversity from the cumulative retention volume-related chronic adversity. Thus, in the absence of kinetically designed studies, it may become increasingly challenging to differentiate substance-specific deposition-related acute effects from the more chronic retained cumulative dose-related effects. It is concluded that the degree of dissolution of particles in the pulmonary environment seems to be generally underestimated with the possibility to attribute to toxicity due to decreased particle size and associated changes in thermodynamics and kinetics of dissolution. Accordingly, acute deposition-related outcomes become an important secondary variable within the pulmonary microenvironment. In turn, lung-overload related chronic adversities seem to be better described by the particle volume metric. This analysis supports the concept that 'self-validating', hypothesis-based computational study design delivers the highest level of unifying information required for the risk characterization of PSP. In demonstrating that the PSP under consideration is truly following the generic PSP-paradigm, this higher level of mechanistic information reduces the potential uncertainty involved with OEL derivation.

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

PubMed

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

2016-02-03

Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low toxicity in oral acute high dose administration and no toxicity in oral sub-chronic low dose administration and indicate that the plants could be considered safe for oral medication in chicks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Alcohol and acute pancreatitis. An experimental study in the rat.

PubMed

Jalovaara, P; Apaja, M

1978-01-01

The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

Design and Analysis of Chronic Aquatic Tests of Toxicity with Daphnia magna.

DTIC Science & Technology

1981-12-01

surface waters. From that need evolved numerous standard toxicity tests. Aquatic toxicologists and biologists developed, refine,, and standard- ized many...experimental categorization summary sheets prepared by Dr. William van der Schalie, which is shown in Table I.I. 7 j-. " .’?, i...partial solution to this dilema can be obtained by studying the effects of the solvent alone. If the solvent by itself produces no toxic responses at

Characteristics of the ToxRefDB In Vivo Datasets from Chronic, Reproductive and Developmental Assays

EPA Science Inventory

ToxRefDB was developed to store data from in vivo animal toxicity studies. The initial focus was populating ToxRefDB with pesticide registration toxicity data that has been historically stored as hard-copy and scanned documents by the Office of Pesticide Programs. A significant p...

75 FR 75682 - Reclassification of Category IIIA Biological Products, Bacterial Vaccines and Related Biological...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... follows: ``Chronic Toxicity Test of SPL in Rats'' (Fujino, et al.) (Ref. 2); ``Acute and Subacute Toxicity Tests of SPL'' (Fujino, et al.) (mice and rats) (Ref. 3); ``Teratologenicity Study of SPL in Rats and... Inoculation with Herpes Simplex Virus'' (Department of Microbiology, School of Medicine, Kyushu University...

TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO ARSENITE OR METHYLARSONOUS ACID

EPA Science Inventory

e metabolism of inorganic arsenic (iAs) in humans yields toxic and carcinogenic methyl-As (MAs) and dimethyl-As (DMAs) intermediates. Methylarsonous acid (MAsIII) is the most acutely toxic species among known iAs metabolites. In this study, we examined the concentrations of As sp...

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). Copyright © 2015 Elsevier Inc. All rights reserved.

Combined endosulfan and cypermethrin-induced toxicity to embryo-larval development of Rhinella arenarum.

PubMed

Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Cristina S

2016-01-01

The combined effects of two widely used pesticides, endosulfan and cypermethrin, on survival of embryo-larval development of the South American toad (Rhinella arenarum) were examined. The toxicity bioassays were performed according to the AMPHITOX test. Embryos and larvae were exposed to mixtures of these pesticides at equitoxic ratios from acute or chronic exposure to evaluate interaction effects. The results were analyzed using both Marking's additive index and combination index (CI)-isobologram methods. Acute (96-h) and intermediate (168-h) toxicity of endosulfan-cypermethrin mixtures remained almost constant for larvae and embryos, but when exposure duration was increased, there was a significant elevation in toxicity, obtaining chronic (240-h) no-observed-effect concentrations (NOEC) values of 0.045 and 0.16 mg/L for embryos and larvae, respectively. These are environmentally relevant concentrations that reflect a realistic risk of this pesticide mixture to this native amphibian species. The toxicity increment with the exposure duration was coincident with the central nervous system development on embryos reaching the larval period, the main target organ of these pesticides. The interactions of the pesticide mixtures at acute and chronic exposure were antagonistic for embryo development (CI > 1), and additive (CI = 1) for larvae, while chronic exposure interactions were synergistic (CI < 1) for both developmental periods. Data indicated that endosulfan-cypermethrin mixtures resulted in different interaction types depending on duration and developmental stage exposed. As a general pattern and considering conditions of overall developmental period and chronic exposure, this pesticide mixture usually applied in Argentine crop fields is synergistic with respect to toxicity for this native amphibian species.

Chronic toxicity of azoxystrobin to freshwater amphipods, midges, cladocerans, and mussels in water-only exposures

USGS Publications Warehouse

Kunz, James L.; Ingersoll, Christopher G.; Smalling, Kelly; Elskus, Adria; Kuivila, Kathryn

2017-01-01

Understanding the effects of fungicides on nontarget organisms at realistic concentrations and exposure durations is vital for determining potential impacts on aquatic ecosystems. Environmental concentrations of the fungicide azoxystrobin have been reported up to 4.6 μg/L in the United States and 30 μg/L in Europe. The objective of the present study was to evaluate the chronic toxicity of azoxystrobin in water-only exposures with an amphipod (Hyalella azteca; 42-d exposure), a midge (Chironomus dilutus; 50-d exposure), a cladoceran (Ceriodaphnia dubia; 7-d exposure), and a unionid mussel (Lampsilis siliquoidea; 28-d exposure) at environmentally relevant concentrations. The potential photo-enhanced toxicity of azoxystrobin accumulated by C. dubiaand L. siliquoidea following chronic exposures to azoxystrobin was also evaluated. The 20% effect concentrations (EC20s) based on the most sensitive endpoint were 4.2 μg/L for H. aztecareproduction, 12 μg/L for C. dubia reproduction and C. dilutus emergence, and >28 μg/L for L. siliquoidea. Hyalella azteca was more sensitive to azoxystrobin compared with the other 3 species in the chronic exposures. No photo-enhanced toxicity was observed for either C. dubia or L. siliquoidea exposed to ultraviolet light in control water following azoxystrobin tests. The results of the present study indicate chronic effects of azoxystrobin on 3 of 4 invertebrates tested at environmentally relevant concentrations. The changes noted in biomass and reproduction have the potential to alter the rate of ecological processes driven by aquatic invertebrates. Environ Toxicol Chem 2017;9999:1–8. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

PREDICTION OF POPULATION-LEVEL RESPONSE FROM MYSID TOXICITY TEST DATA USING POPULATION MODEL TECHNIQUES

EPA Science Inventory

Acute and chronic bioassay statistics are used to evaluate the toxicity and the risks of chemical stressors to mysid shrimp Americamysis bahia (formerly Mysidopsis bahia). These include LC50 values from acute tests, chronic values (the geometric mean of the no-obsderved-effect co...

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 ...

Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles.

PubMed

Natale, G S; Ammassari, L L; Basso, N G; Ronco, A E

2006-10-27

In the last few years there has been great concern about declines in the abundance of several species of amphibians around the world. Among amphibians, anurans have a biphasic life cycle, with aquatic tadpoles and generally terrestrial adults, and they have an extremely permeable skin, making them excellent indicators of the health of the environment. A number of different causes have been suggested for the global decline of anurans, the pollution of their habitat by chemical stressors being considered one of the major factors. Among chemical stressors, heavy metals are known for their high toxicity at very low concentrations. This study assessed short- (96 h, 'acute') and long-term (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg 1(-1)) and sublethal concentrations (0.001 to 12 mg 1(-1)) on Hypsiboaspulchellus (previously called Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central eastern Argentina. Fertilized eggs collected from a clean pond near La Plata (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays were done under controlled laboratory conditions. Results of chronic exposure were used to assess the effect of factors such as toxicant concentration and age of organisms at the beginning of exposure on the response variables (growth, development and survival until metamorphosis). Results indicated a higher sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first exposed as embryos during acute and chronic exposure. Exposure to the highest sublethal concentrations (6 to 12 mg 1(-1)) of the toxicant showed early inhibitory effects on growth of all treated organisms compensated at longer exposure periods with an increase in the growth rate compared to the control groups.

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

PubMed

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

2018-01-01

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

Classification and Dose-Response Characterization of ...

EPA Pesticide Factsheets

Thirty years and over a billion of today’s dollars worth of pesticide registration toxicity studies, historically stored as hardcopy and scanned documents, have been digitized into highly standardized and structured toxicity data, within the U.S. Environmental Protection Agency’s (EPA) Toxicity Reference Database (ToxRefDB). The source toxicity data in ToxRefDB covers multiple study types, including subchronic, developmental, reproductive, chronic, and cancer studies, resulting in a diverse set of endpoints and toxicities. Novel approaches to chemical classification are performed as a model application of ToxRefDB and as an essential need for highly detailed chemical classifications within the EPA’s ToxCast™ research program. In order to develop predictive models and biological signatures utilizing high-throughput screening (HTS) and in vitro genomic data, endpoints and toxicities must first be identified and globally characterized for ToxCast Phase I chemicals. Secondarily, dose-response characterization within and across toxicity endpoints provide insight into key precursor toxicity events and overall endpoint relevance. Toxicity-based chemical classification and dose-response characterization utilizing ToxRefDB prioritized toxicity endpoints and differentiated toxicity outcomes across a large chemical set.

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

USGS Publications Warehouse

Farag, Aïda 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.

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.

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

PubMed

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

2013-11-01

This study evaluated the chronic toxicity of Ni-spiked freshwater sediments to benthic invertebrates. A 2-step spiking procedure (spiking and sediment dilution) and a 2-stage equilibration period (10 wk anaerobic and 1 wk aerobic) were used to spike 8 freshwater sediments with wide ranges of acid-volatile sulfide (AVS; 0.94-38 µmol/g) and total organic carbon (TOC; 0.42-10%). Chronic sediment toxicity tests were conducted with 8 invertebrates (Hyalella azteca, Gammarus pseudolimnaeus, Chironomus riparius, Chironomus dilutus, Hexagenia sp., Lumbriculus variegatus, Tubifex tubifex, and Lampsilis siliquoidea) in 2 spiked sediments. Nickel toxicity thresholds estimated from species-sensitivity distributions were 97 µg/g and 752 µg/g (total recoverable Ni; dry wt basis) for sediments with low and high concentrations of AVS and TOC, respectively. Sensitive species were tested with 6 additional sediments. The 20% effect concentrations (EC20s) for Hyalella and Gammarus, but not Hexagenia, were consistent with US Environmental Protection Agency benchmarks based on Ni in porewater and in simultaneously extracted metals (SEM) normalized to AVS and TOC. For Hexagenia, sediment EC20s increased at less than an equimolar basis with increased AVS, and toxicity occurred in several sediments with Ni concentrations in SEM less than AVS. The authors hypothesize that circulation of oxygenated water by Hexagenia led to oxidation of AVS in burrows, creating microenvironments with high Ni exposure. Despite these unexpected results, a strong relationship between Hexagenia EC20s and AVS could provide a basis for conservative site-specific sediment quality guidelines for Ni. © 2013 SETAC.

Effect of the lipid regulator Gemfibrozil in the Cladocera Daphnia magna at different temperatures.

PubMed

Salesa, Beatriz; Ferrando, María D; Villarroel, María J; Sancho, Encarna

2017-02-23

In the present study, an ecotoxicological approach to the evaluation of Gemfibrozil (GEM) as an emerging organic pollutant was done. In order to assess its toxicity, tests were conducted using the cladocera Daphnia magna. Experiments were carried out at 22°C and 28°C. EC 50 , feeding behavior, and chronic toxicity tests (21 days) were evaluated in D. magna exposed to GEM as well as cholesterol levels at 21-day chronic exposure. D. magna GEM EC 50 values (24 h) in our experimental conditions were 148.75 and 116.24 mg L -1 at 22°C and 28°C, respectively. Test concentrations of 0.1, 0.5, 1.0, 5.0 and 7.5 mg L -1 were selected for subacute and chronic experiments. Subacute short-term test (feeding study) was assessed after exposure to the toxicant. Filtration and ingestion rates of D. magna exposed animals did not show any significant difference (P > 0.05) with respect to control daphniids neither at 22°C nor at 28°C. Therefore, GEM test concentrations used in the present study did not reduce feeding behavior in D. magna. Temperature increased from 22°C to 28°C, which resulted in a decrease of the daphniids reproductive parameters such as brood size and number of young per female. Other parameters as longevity were not affected. The GEM concentrations used in the chronic test with D. magna did not affect daphniids longevity but some reproductive parameters as number of young per female or brood size were affected. Finally, a significant decreased in cholesterol levels was found in those animals exposed to the highest toxicant concentrations. More studies must be done to determine the possible implications of GEM in aquatic fauna and to derive its possible effects on the environment.

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

[Staphylococcal toxic shock syndrome at a chronic hemodialysis].

PubMed

Alaoui, Hassan; Belhadj, Ayoub; Aissaoui, Younes; Seddiki, Rachid; Zoubir, Mohamed; Bougalem, Mohamed

2017-01-01

Staphylococcal toxic shock syndrome is an acute and systemic infectious syndrome associated with the super-antigenic activity of staphylococcal toxins. It is a pathology that is rather rare but remains burdened with a considerable mortality despite the therapeutic management. The gateway is usually cutaneous with secondary bacteremic spread could be subject to preventive measures. We report the case of a rapidly fatal staphylococcal toxic shock, developed in a chronic hemodialysis whose entry from the arteriovenous fistula was suspected.

A retrospective analysis of toxicity studies in dogs and impact on the chronic reference dose for conventional pesticide chemicals.

PubMed

Dellarco, Vicki L; Rowland, Jess; May, Brenda

2010-01-01

Prior to October 2007, the US Environmental Protection Agency (EPA) required both 13-week and 1-year studies in Beagle dogs be submitted in support of registration for pesticides. Following an extensive retrospective analysis, we (the authors) determined that the 1-year toxicity dog study should be eliminated as a requirement for pesticide registration. The present work presents this retrospective analysis of results from 13-week and 1-year dog studies for 110 conventional pesticide chemicals, representing more than 50 classes of pesticides. The data were evaluated to determine if the 13-week dog study, in addition to the long-term studies in two rodent species (mice and rats), were sufficient for the identification of no observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) for the derivation of chronic reference doses (RfD). Only pesticides with adequate 13-week and 1-year duration studies were included in the present evaluation. Toxicity endpoints and dose-response data from 13-week and 1-year studies were compared. The analysis showed that 70 of the 110 pesticides had similar critical effects regardless of duration and had NOAELs and LOAELs within a difference of 1.5-fold of each other. For the remaining 40 pesticides, 31 had lower NOAELs and LOAELs in the 1-year study, primarily due to dose selection and spacing. In only 2% of the cases were additional toxic effects identified in the 1-year study that were not observed in the 13-week study and/or in the rodent studies. In 8% of the cases, the 1-year dog had a lower NOAEL and/or LOAEL than the 13-week study, but there would have been no regulatory impact if the 1-year dog study had not been performed because adequate data were available from the other required studies. A dog toxicity study beyond 13-weeks does not have significant impact on the derivation of a chronic RfD for pesticide risk assessment.

Observed and predicted reproduction of Ceriodaphnia dubia exposed to chloride, sulfate, and bicarbonate

USGS Publications Warehouse

Lasier, Peter J.; Hardin, Ian R.

2010-01-01

Chronic toxicities of Cl-, SO42-, and HCO3- to Ceriodaphnia dubia were evaluated in low- and moderate-hardness waters using a three-brood reproduction test method. Toxicity tests of anion mixtures were used to determine interaction effects and to produce models predicting C. dubia reproduction. Effluents diluted with low- and moderate-hardness waters were tested with animals acclimated to low- and moderate-hardness conditions to evaluate the models and to assess the effects of hardness and acclimation. Sulfate was significantly less toxic than Cl- and HCO3- in both types of water. Chloride and HCO3- toxicities were similar in low-hardness water, but HCO3- was the most toxic in moderate-hardness water. Low acute-to-chronic ratios indicate that toxicities of these anions will decrease quickly with dilution. Hardness significantly reduced Cl- and SO42- toxicity but had little effect on HCO3-. Chloride toxicity decreased with an increase in Na+ concentration, and CO3- toxicity may have been reduced by the dissolved organic carbon in effluent. Multivariate models using measured anion concentrations in effluents with low to moderate hardness levels provided fairly accurate predictions of reproduction. Determinations of toxicity for several effluents differed significantly depending on the hardness of the dilution water and the hardness of the water used to culture test animals. These results can be used to predict the contribution of elevated anion concentrations to the chronic toxicity of effluents; to identify effluents that are toxic due to contaminants other than Cl-, SO42-, and HCO3-; and to provide a basis for chemical substitutions in manufacturing processes.

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. © 2013 SETAC.

USE OF TOXICITY IDENTIFICATION EVALUATION METHODS TO CHARACTERIZE IDENTIFY, AND CONFIRM HEXAVALENT CHROMIUM TOXICITY IN AN INDUSTRIAL EFFLUENT

EPA Science Inventory

A toxicity identification evaluation (TIE) was conducted on effluent from a major industrial discharger. Initial monitoring showed slight chronic toxicity to Ceriodaphnia dubia; later sample showed substantial toxicity to C. dubia. Chemical analysis detected hexavalent chromium ...

A review of environmental impacts of salts from produced waters on aquatic resources

USGS Publications Warehouse

Farag, Aïda M.; Harper, David D.

2014-01-01

Salts are frequently a major constituent of waste waters produced during oil and gas production. These produced waters or brines must be treated and/or disposed and provide a daily challenge for operators and resource managers. Some elements of salts are regulated with water quality criteria established for the protection of aquatic wildlife, e.g. chloride (Cl−), which has an acute standard of 860 mg/L and a chronic standard of 230 mg/L. However, data for establishing such standards has only recently been studied for other components of produced water, such as bicarbonate (HCO3−), which has acute median lethal concentrations (LC50s) ranging from 699 to > 8000 mg/L and effects on chronic toxicity from 430 to 657 mg/L. While Cl− is an ion of considerable importance in multiple geographical regions, knowledge about the effects of hardness (calcium and magnesium) on its toxicity and about mechanisms of toxicity is not well understood. A multiple-approach design that combines studies of both individuals and populations, conducted both in the laboratory and the field, was used to study toxic effects of bicarbonate (as NaHCO3). This approach allowed interpretations about mechanisms related to growth effects at the individual level that could affect populations in the wild. However, additional mechanistic data for HCO3−, related to the interactions of calcium (Ca2 +) precipitation at the microenvironment of the gill would dramatically increase the scientific knowledge base about how NaHCO3 might affect aquatic life. Studies of the effects of mixtures of multiple salts present in produced waters and more chronic effect studies would give a better picture of the overall potential toxicity of these ions. Organic constituents in hydraulic fracturing fluids, flowback waters, etc. are a concern because of their carcinogenic properties and this paper is not meant to minimize the importance of maintaining vigilance with respect to potential organic contamination.

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 for possible effects on fertility (or early embryonic development), the biological significance of which can be ascertained in a littering (e.g. 2-generation) study. From the chemicals reviewed it would appear that where there are no alerts from a repeat-dose toxicity study, a pre-natal developmental toxicity study and sex steroid receptor binding assays, there exists a low priority for animal studies to address the fertility endpoint. The ability for these types of tests to provide alerts for effects on fertility is clearly dependent on the mode of action of the toxicant in question. Further work should therefore be performed to determine the 'failure rate' of this type of approach when applied to a larger group of chemicals with diverse modes of action.

Role of Alcohol Metabolism in Chronic Pancreatitis

PubMed Central

Vonlaufen, Alain; Wilson, Jeremy S.; Pirola, Romano C.; Apte, Minoti V.

2007-01-01

Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis of alcoholic pancreatitis was related to ductular and sphincteric abnormalities. In recent years, the focus has shifted to the type of pancreas cell that produces digestive juices (i.e., acinar cell). Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and nonoxidative pathways. The isolation and study of pancreatic stellate cells (PSCs)—the key effectors in the development of connective tissue fibers (i.e., fibrogenesis) in the pancreas—has greatly enhanced our understanding of the pathogenesis of chronic pancreatitis. Pancreatic stellate cells become activated in response to ethanol and acetaldehyde, a toxic byproduct of alcohol metabolism. In addition, PSCs have the capacity to metabolize alcohol via alcohol dehydrogenase (the major oxidizing enzyme for ethanol). The fact that only a small percentage of heavy alcoholics develop chronic pancreatitis has led to the search for precipitating factors of the disease. Several studies have investigated whether variations in ethanol-metabolizing enzymes may be a trigger factor for chronic pancreatitis, but no definite relationship has been established so far. PMID:17718401

Characteristics and Applications of the ToxRefDB In Vivo Datasets from Chronic, Reproductive and Developmental Assays

EPA Science Inventory

ToxRefDB was developed to store data from in vivo animal toxicity studies. The initial focus was populating ToxRefDB with pesticide registration toxicity data that has been historically stored as hard-copy and scanned documents by the Office of Pesticide Programs. A significant p...

An assessment of two-step linear regression and a multifactor probit analysis as alternatives to acute to chronic ratios in the estimation of chronic response from acute toxicity data to derive water quality guidelines.

PubMed

Slaughter, Andrew R; Palmer, Carolyn G; Muller, Wilhelmine J

2007-04-01

In aquatic ecotoxicology, acute to chronic ratios (ACRs) are often used to predict chronic responses from available acute data to derive water quality guidelines, despite many problems associated with this method. This paper explores the comparative protectiveness and accuracy of predicted guideline values derived from the ACR, linear regression analysis (LRA), and multifactor probit analysis (MPA) extrapolation methods applied to acute toxicity data for aquatic macroinvertebrates. Although the authors of the LRA and MPA methods advocate the use of extrapolated lethal effects in the 0.01% to 10% lethal concentration (LC0.01-LC10) range to predict safe chronic exposure levels to toxicants, the use of an extrapolated LC50 value divided by a safety factor of 5 was in addition explored here because of higher statistical confidence surrounding the LC50 value. The LRA LC50/5 method was found to compare most favorably with available experimental chronic toxicity data and was therefore most likely to be sufficiently protective, although further validation with the use of additional species is needed. Values derived by the ACR method were the least protective. It is suggested that there is an argument for the replacement of ACRs in developing water quality guidelines by the LRA LC50/5 method.

Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

PubMed

Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

2017-02-05

The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive-Dosing Methods and Target-Lipid and Chemical-Activity Models.

PubMed

Butler, Josh D; Parkerton, Thomas F; Redman, Aaron D; Letinski, Daniel J; Cooper, Keith R

2016-08-02

Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More-hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated.

PREDICTING CHRONIC LETHALITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: THEORY OF ACCELERATED LIFE TESTING

EPA Science Inventory

A method for modeling aquatic toxicity date based on the theory of accelerated life testing and a procedure for maximum likelihood fitting the proposed model is presented. he procedure is computerized as software, which can predict chronic lethality of chemicals using data from a...

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)

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...

TOXICITY IDENTIFICATION EVALUATION WORKSHOP-PART II: WHAT WORKS, WHAT DOESN'T, AND DEVELOPMENTS FOR EFFLUENTS AND AQUEOUS MEDIA

EPA Science Inventory

Toxicity reduction evaluations (TRE) and Toxicity Identification Evaluations (TIE) case examples were the basis of a technical workshop held by SETAC. Techniques to evaluate the mixtures of toxicants by using acute and chronic toxicity endpoints that incorporate marine, estuarine...

Oral ketamine for children with chronic pain: a pilot phase 1 study

PubMed Central

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals.

PubMed

Thomas, Paul; Dawick, James; Lampi, Mark; Lemaire, Philippe; Presow, Shaun; van Egmond, Roger; Arnot, Jon A; Mackay, Donald; Mayer, Philipp; Galay Burgos, Malyka

2015-10-20

Toxicological research in the 1930s gave the first indications of the link between narcotic toxicity and the chemical activity of organic chemicals. More recently, chemical activity has been proposed as a novel exposure parameter that describes the fraction of saturation and that quantifies the potential for partitioning and diffusive uptake. In the present study, more than 2000 acute and chronic algal, aquatic invertebrates and fish toxicity data, as well as water solubility and melting point values, were collected from a series of sources. The data were critically reviewed and grouped by mode of action (MoA). We considered 660 toxicity data to be of acceptable quality. The 328 data which applied to the 72 substances identified as MoA 1 were then evaluated within the activity-toxicity framework: EC50 and LC50 values for all three taxa correlated generally well with (subcooled) liquid solubilities. Acute toxicity was typically exerted within the chemical activity range of 0.01-0.1, whereas chronic toxicity was exerted in the range of 0.001-0.01. These results confirm that chemical activity has the potential to contribute to the determination, interpretation and prediction of toxicity to aquatic organisms. It also has the potential to enhance regulation of organic chemicals by linking results from laboratory tests, monitoring and modeling programs. The framework can provide an additional line of evidence for assessing aquatic toxicity, for improving the design of toxicity tests, reducing animal usage and addressing chemical mixtures.

High levels of heavy metal accumulation in dental calculus of smokers: a pilot inductively coupled plasma mass spectrometry study.

PubMed

Yaprak, E; Yolcubal, I; Sinanoğlu, A; Doğrul-Demiray, A; Guzeldemir-Akcakanat, E; Marakoğlu, I

2017-02-01

Various trace elements, including toxic heavy metals, may exist in dental calculus. However, the effect of environmental factors on heavy metal composition of dental calculus is unknown. Smoking is a major environmental source for chronic toxic heavy metal exposition. The aim of this study is to compare toxic heavy metal accumulation levels in supragingival dental calculus of smokers and non-smokers. A total of 29 supragingival dental calculus samples were obtained from non-smoker (n = 14) and smoker (n = 15) individuals. Subjects with a probability of occupational exposure were excluded from the study. Samples were analyzed by inductively coupled plasma mass spectrometry in terms of 26 metals and metalloids, including toxic heavy metals. Toxic heavy metals, arsenic (p < 0.05), cadmium (p < 0.05), lead (p < 0.01), manganese (p < 0.01) and vanadium (p < 0.01) levels were significantly higher in smokers than non-smokers. The levels of other examined elements were similar in both groups (p > 0.05). Within the limitations of this study, it can be concluded that the elementary composition of dental calculus may be affected by environmental factors such as tobacco smoke. Therefore, dental calculus may be utilized as a non-invasive diagnostic biological material for monitoring chronic oral heavy metal exposition. However, further studies are required to evaluate its diagnostic potential. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute and early life stage toxicity of industrial effluent on Japanese medaka (Oryzias latipes).

PubMed

Zha, Jinmiao; Wang, Zijian

2006-03-15

To develop the whole effluent toxicity testing methods (WET), embryo larval stage toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate an effluent from a banknote printing plant (BPP). The method is based on acute toxicity using endpoint of 96-h larval morality and on chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old) were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200 mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post-hatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. A reduction in body weight was observed at 25% dilutions for males and females, respectively. Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. We conclude that embryo larval stage test using medaka is feasible to evaluate both acute and chronic toxicities and potential endocrine disrupting activity of industrial effluents.

Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome.

PubMed

Iurlo, Alessandra; Nobili, Alessandro; Latagliata, Roberto; Bucelli, Cristina; Castagnetti, Fausto; Breccia, Massimo; Abruzzese, Elisabetta; Cattaneo, Daniele; Fava, Carmen; Ferrero, Dario; Gozzini, Antonella; Bonifacio, Massimiliano; Tiribelli, Mario; Pregno, Patrizia; Stagno, Fabio; Vigneri, Paolo; Annunziata, Mario; Cavazzini, Francesco; Binotto, Gianni; Mansueto, Giovanna; Russo, Sabina; Falzetti, Franca; Montefusco, Enrico; Gugliotta, Gabriele; Storti, Sergio; D'Addosio, Ada M; Scaffidi, Luigi; Cortesi, Laura; Cedrone, Michele; Rossi, Antonella Russo; Avanzini, Paolo; Mauro, Endri; Spadea, Antonio; Celesti, Francesca; Giglio, Gianfranco; Isidori, Alessandro; Crugnola, Monica; Calistri, Elisabetta; Sorà, Federica; Rege-Cambrin, Giovanna; Sica, Simona; Luciano, Luigiana; Galimberti, Sara; Orlandi, Ester M; Bocchia, Monica; Tettamanti, Mauro; Alimena, Giuliana; Saglio, Giuseppe; Rosti, Gianantonio; Mannucci, Pier Mannuccio; Cortelezzi, Agostino

2016-11-29

About 40% of all patients with chronic myeloid leukemia are currently old or very old. They are effectively treated with imatinib, even though underrepresented in clinical studies. Furthermore, as it happens in the general population, they often receive multiple drugs for associated chronic illnesses. Aim of this study was to assess whether or not in imatinib-treated patients aged >75 years the exposure to polypharmacy (5 drugs or more) had an impact on cytogenetic and molecular response rates, event-free and overall survival, as well as on hematological or extra-hematological toxicity. 296 patients at 35 Italian hematological institutions were evaluated. Polypharmacy was reported in 107 patients (36.1%), and drugs more frequently used were antiplatelets, diuretics, proton pump inhibitors, ACE-inhibitors, beta-blockers, calcium channel blockers, angiotensin II receptors blockers, statins, oral hypoglycemic drugs and alpha blockers. Complete cytogenetic response was obtained in 174 patients (58.8%), 78 (26.4%) within 6 month, 63 (21.3%) between 7 and 12 months. Major molecular response was obtained in 153 patients (51.7%), 64 (21.6%) within the 12 month. One hundred and twenty-eight cases (43.2%) of hematological toxicity were recorded, together with 167 cases (56.4%) of extra-hematological toxicity. Comparing patients exposed to polypharmacy to those without, no difference was observed pertaining to the dosage of imatinib, cytogenetic and molecular responses and hematological and extra-hematological toxicity. Notwithstanding the several interactions reported in the literature between imatinib and some of the medications considered herewith, this fact does not seem to have a clinical impact on response rate and outcome.

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 in traditional medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia.

PubMed

El-Ansary, Afaf K; Bacha, Abir Ben; Ayahdi, Layla Y Al-

2011-09-01

This study aims to clarify the relationship between blood Pb(2+) concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. RBC's lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb(2+) and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples. Copyright © 2011. Published by Elsevier Inc.

Regenerative toxicology: the role of stem cells in the development of chronic toxicities.

PubMed

Canovas-Jorda, David; Louisse, Jochem; Pistollato, Francesca; Zagoura, Dimitra; Bremer, Susanne

2014-01-01

Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.

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 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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00699b

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...

Symptoms and implications of selenium toxicity in fish: the Belews Lake case example

Treesearch

A. Dennis Lemly

2002-01-01

Belews Lake, North Carolina was contaminated by selenium in wastewater from a coal-fired power plant during the mid-1970s and toxic impacts to the resident fish community (20 species) were studied for over two decades. Symptoms of chronic selcnitun poisoning in Belews Lake fish included, (1) telangiectasia (swelling) of gill lamellae; (2) elevated lymphocytes; (3)...

TOXICITY IDENTIFICATION EVALUATION OF A WASTEWATER TREATMENT PLANT EFFLUENT WITH IONIC TOXICANTS

EPA Science Inventory

A publicly owned treatment works (POTW) effluent had been shown to cause chronic toxicity with the cladoceran, Ceriodaphnia dubia. We conducted A TIE and the weight-of-evidence approach identified chloride as a major contributor to the effluent toxicity. Several characterization...

Combination of nanofiltration and ozonation for the remediation of real municipal wastewater effluents: Acute and chronic toxicity assessment.

PubMed

Miralles-Cuevas, S; Oller, I; Agüera, A; Llorca, M; Sánchez Pérez, J A; Malato, S

2017-02-05

The purpose of this work was to study the ozonation of nanofiltration (NF) retentates of real municipal wastewater treatment plant (MWTP) effluents for removal of microcontaminants (MCs) and toxicity. MCs present in these effluents were monitored using LC-MS/MS. Acute and chronic toxicity was addressed with Daphnia magna, Vibrio fischeri and Selenastrum capricornutum. Up to 40 MCs were found, most of them in concentrations over 100ng/L. 90% degradation of the sum of MCs was the critical point of comparison. When the NF membrane system was applied to MWTP effluents, treatment of NF rejection needed 2.75-4.5g O 3 /m 3 ,4.5g O 3 /m 3 , which is less than 50% of the ozone needed for direct treatment of MWTP effluent. Treatment time (lower than 11min) was not influenced by MCs concentration, at least in the range tested (25-190μg/L). It has been demonstrated that consumption of ozone increased with organic load and inorganic content of different real effluents. MCs were eliminated by ozonation but acute toxicity (against V. fischeri and D. magna) increased. Chronic toxicity results were different and contrary in D. magna and S. capricornutum, due to the generation of new transformation products more toxic to D. magna than the parent contaminants. S. capricornutum inhibition percentage decreased in all cases after ozonation treatment. According to these results, before ozonation is implemented in MWTPs for the removal of MCs, the transformation products must first be examined and the treatment time or ozone doses should be extended to complete degradation if necessary. Copyright © 2016 Elsevier B.V. All rights reserved.

Ecotoxicological evaluation of industrial port of Venice (Italy) sediment samples after a decontamination treatment.

PubMed

Libralato, Giovanni; Losso, Chiara; Arizzi Novelli, Alessandra; Citron, Marta; Della Sala, Stefano; Zanotto, Emanuele; Cepak, Franka; Volpi Ghirardini, Annamaria

2008-12-01

This work assesses the ecotoxicological effects of polluted sediment after a decontamination treatment process using a new sediment washing technique. Sediment samples were collected from four sites in Marghera Port industrial channels (Venice, Italy). Ecotoxicological evaluations were performed with Vibrio fischeri and Crassostrea gigas bioassays. Whole sediment and elutriate were deemed as the most suitable environmental matrices for this study. Toxicity scores developed in the Lagoon of Venice for V. fischeri on whole sediment and for C. gigas on elutriate were considered for the final ranking of samples. Ecotoxicological results showed that the treated sediment samples presented both acute and sub-chronic toxicities, which were mainly attributed to the presence of some remaining chemicals such as metals and polyaromatic hydrocarbons. The acute toxicity ranged from low to medium, while the sub-chronic one from absent to very high, suggesting that treated sediments could not be reused in direct contact with seawater.

Meta-analysis of fish early life stage tests-Association of toxic ratios and acute-to-chronic ratios with modes of action.

PubMed

Scholz, Stefan; Schreiber, Rene; Armitage, James; Mayer, Philipp; Escher, Beate I; Lidzba, Annegret; Léonard, Marc; Altenburger, Rolf

2018-04-01

Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 × 10 4 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin formation < endocrine disruption < extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955-969. © 2018 SETAC. © 2018 SETAC.

Different modes of TiO2 uptake by Ceriodaphnia dubia: relevance to toxicity and bioaccumulation.

PubMed

Dalai, Swayamprava; Iswarya, V; Bhuvaneshwari, M; Pakrashi, Sunandan; Chandrasekaran, N; Mukherjee, Amitava

2014-07-01

The extensive environmental exposure of engineered metal oxide nanoparticles (NPs) may result in their bioaccumulation in aquatic organisms leading to their biotransfer in a food chain through various routes in a freshwater ecosystem. The present study focuses on the possible modes of TiO2 NP trophic transfer to Ceriodaphnia dubia, in presence and/absence of its diet, Scenedesmus obliquus (primary producer). The acute exposure studies (48h) were designed to have daphnids exposed to (i) the free NPs, (ii) both the free and the algae-borne NPs; and (iii) only the algae-borne NPs in separate tests to understand the possible routes of NP transfer. The dietary uptake of TiO2 NPs (algae-borne) was found to be the primary route for NP biotransfer with ∼70% of total NP uptake. Interestingly, in a separate study it was noticed that the NPs coated with algal exudates were easily taken up by daphnids as compared to pristine NPs of same concentrations, leading to their higher bioaccumulation. A chronic toxicity study, where daphnids were exposed to both free and algae-borne NPs for 21 days was undertaken to comprehend the TiO2 NP effect on daphnia growth and reproduction upon chronic exposure and also the bioaccumulation potential. Both acute and chronic exposure studies suggested higher bioaccumulation of TiO2 in daphnids when the particles were less toxic to the diet (algae). Copyright © 2014 Elsevier B.V. All rights reserved.

An ecotoxicological approach for hazard identification of energy ash.

PubMed

Stiernström, S; Hemström, K; Wik, O; Carlsson, G; Bengtsson, B-E; Breitholtz, M

2011-02-01

Within the EU, ash should be classified by its inherent hazardous effects under criterion H-14 (ecotoxic) in the Directive on waste (2008/98/EC). Today, however, there are no harmonized quantitative criterions for such a classification, but it is stated that biological test systems can be used. In this study seven ash materials were leached and characterized, both biologically and chemically. The objectives were to evaluate if (a) clear concentration-response relationships could be achieved for the selected toxicity tests (bacteria, algae, crustacean and fish), (b) some test(s) are generally more sensitive and (c) the toxic responses were consistent with the chemical analyzes. Interestingly, our results indicate that high concentrations of non-hazardous components (Ca, K) influenced the toxicity of almost all ash eluates, whereas hazardous components (e.g. Zn, Pb) only influenced the toxicity of the eluates ranked as most hazardous. If considering both hazardous and non-hazardous substances, the observed toxic responses were relatively consistent with the chemical analyzes. Our results further showed that the (sub)chronic tests were much more sensitive than the acute tests. However, the use of extrapolation factors to compensate for using the less sensitive acute tests will likely lead to either over- or underestimations of toxicity. Our recommendation is therefore that classification of waste according to H-14 should be based on (sub)chronic test data. Finally, given that treatment of the eluates prior to toxicity testing has a major significance on the concentration and speciation of released substances, further studies are needed in order to propose a relevant testing scheme. Copyright © 2010 Elsevier Ltd. All rights reserved.

Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

PubMed

Lohiya, Nirmal K; Manivannan, Boomi; Garg, Shipra

2006-10-01

Pre-clinical acute and sub-chronic toxicity studies of the methanol sub-fraction (MSF) of the seeds of Carica papaya, a putative male contraceptive, have been investigated in rats to evaluate safety of the test substance. A single oral dose of MSF at 2000 mg/kg body weight was studied over 14 days for acute toxicity, and daily oral doses of 50, 100, 250 and 500 mg/kg body weight were studied for 28- and 90-day periods for sub-chronic toxicity. Body weight, food and water intake and phenotypical toxicological symptoms were recorded daily. Sperm analysis, hematology, serum clinical biochemistry, libido and pathological examination of vital organs were recorded at the termination of the experimental periods. We observed no overt general toxicity in exposed animals. Food and water intake showed daily fluctuations within control limits. Sperm density showed a significant decrease in all 28- and 90-day repeated dose treated animals whereas total sperm motility inhibition was observed at 250 and 500 mg/kg dose levels at the 28-day time interval but in all dose groups at the 90-day interval. The preliminary results suggest the test substance may be a safe approach to male anti-fertility.

The Blue Coma: The Role of Methylene Blue in Unexplained Coma After Cardiac Surgery.

PubMed

Martino, Enrico Antonio; Winterton, Dario; Nardelli, Pasquale; Pasin, Laura; Calabrò, Maria Grazia; Bove, Tiziana; Fanelli, Giovanna; Zangrillo, Alberto; Landoni, Giovanni

2016-04-01

Methylene blue commonly is used as a dye or an antidote, but also can be used off label as a vasopressor. Serotonin toxicity is a potentially lethal and often misdiagnosed condition that can result from drug interaction. Mild serotonin toxicity previously was reported in settings in which methylene blue was used as a dye. The authors report 3 cases of life-threatening serotonin toxicity in patients undergoing chronic selective serotonin reuptake inhibitor (SSRI) therapy who also underwent cardiac surgery and received methylene blue to treat vasoplegic syndrome. An observational study. A cardiothoracic intensive care unit (ICU) in a teaching hospital. Three patients who received methylene blue after cardiac surgery, later discovered to be undergoing chronic SSRI therapy. None. All 3 patients received high doses of fentanyl during general anesthesia. They all developed vasoplegic syndrome and consequently were given methylene blue in the ICU. All 3 patients developed serotonin toxicity, including coma, after this administration and diagnostic tests were negative for acute intracranial pathology. Coma lasted between 1 and 5 days. Two patients were discharged from the ICU shortly after awakening, whereas the third patient experienced a complicated postoperative course for concomitant refractory low-cardiac-output syndrome. Patients undergoing chronic SSRI therapy should not be administered methylene blue to treat vasoplegic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

PubMed

Wang, Ning; Ingersoll, Christopher G; Ivey, Christopher D; Hardesty, Douglas K; May, Thomas W; Augspurger, Tom; Roberts, Andy D; van Genderen, Eric; Barnhart, M Chris

2010-09-01

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 microg Pb/L, >227 microg Cd/L, 2,685 microg Zn/L) and 96-h EC50s for two- or six-month-old fatmucket (>426 microg Pb/L, 199 microg Cd/L, 1,700 microg Zn/L) were much higher than 96-h EC50s for newly transformed fatmucket (142 and 298 microg Pb/L, 16 microg Cd/L, 151 and 175 microg Zn/L) and Neosho mucket (188 microg Pb/L, 20 microg Cd/L, 145 microg Zn/L). Chronic values for fatmucket were 10 microg Pb/L, 6.0 microg Cd/L, and 63 and 68 microg 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. Copyright 2010 SETAC.

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jawad, Maha Saada; Dilworth, Joshua T.; Gustafson, Gary S.

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0.more » The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ{sup 2} test. P values <.05 were considered significant. Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.« less

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

USGS Publications Warehouse

Meinertz, Jeffery R.; Schreier, Theresa M.; Bernardy, Jeffry A.; Franz, Jeanne L.

2011-01-01

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 μg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 μg/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 μg/L and for ET was 248 μg/L.

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,...

Assessing the chronic toxicity of nickel to a tropical marine gastropod and two crustaceans.

PubMed

Gissi, Francesca; Stauber, Jenny L; Binet, Monique T; Trenfield, Melanie A; Van Dam, Joost W; Jolley, Dianne F

2018-09-15

The mining and processing of nickel ores from tropical regions contributes 40% of the global supply. The potential impact of these activities on tropical marine ecosystems is poorly understood. Due to the lack of ecotoxicity data for tropical marine species, there is currently no available water quality guideline value for nickel that is specific to tropical species. In this study, we investigated the toxicity of nickel to three tropical marine invertebrates, the gastropod Nassarius dorsatus, the barnacle Amphibalanus amphitrite, and the copepod Acartia sinjiensis. All toxicity tests used chronic endpoints, namely larval growth, metamorphosis (transition from nauplii to cyprid larvae) and larval development for the snail, barnacle and copepod respectively. Toxicity tests were carried out under environmentally relevant conditions (i.e. 27-30ᵒC, salinity 34-36‰, pH 8.1-8.4). Copper was also tested for quality assurance purposes and to allow for comparisons with previous studies. The copepod was the most sensitive species to nickel, with development inhibited by 10% (EC10) at 5.5 (5.0-6.0) µg Ni/L (95% confidence limits (CL)). Based on EC10 values, the gastropod and barnacle showed similar sensitivities to nickel with growth and metamorphosis inhibited by 10% at 64 (37-91) µg Ni/L and 67 (53-80) µg Ni/L, respectively. Based on existing data available in the literature, the copepod A. sinjiensis is so far the most sensitive tropical marine species to nickel. This study has provided high quality data which will contribute to the development of a water quality guideline value for nickel in tropical marine waters. A species sensitivity distribution of chronic nickel toxicity used the data generated in this paper supplemented by available literature data, comprising 12 species representing 6 taxonomic groups. A 5% hazard concentration (HC5) was determined as 8.2 µg/L Ni. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects

PubMed Central

Cronin, Mark T.D.; Enoch, Steven J.; Mellor, Claire L.; Przybylak, Katarzyna R.; Richarz, Andrea-Nicole; Madden, Judith C.

2017-01-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given. PMID:28744348

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects.

PubMed

Cronin, Mark T D; Enoch, Steven J; Mellor, Claire L; Przybylak, Katarzyna R; Richarz, Andrea-Nicole; Madden, Judith C

2017-07-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.

Principles and Procedures for Evaluating the Toxicity of Household Substances. Revised.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Assembly of Life Sciences.

This report was prepared for use by the professional toxicologist. It contains chapters on ingestion exposure, dermal and dye toxicity tests, inhalation exposure, chronic toxicity and carcinogenicity tests, mutagenicity tests, reproduction and teratogenicity tests, and behavioral toxicity tests. In addition, regulations under the Federal Hazardous…

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of the toxicity of the Brazilian pepper trees Schinus terebinthifolius Raddi (Aroeira-da-praia) and Myracrodruon urundeuva Allemão (Aroeira-do-sertão).

PubMed

Carlini, Elisaldo Araujo; Duarte-Almeida, Joaquim Maurício; Tabach, Ricardo

2013-05-01

The present study aimed to assess the preclinical toxicity of two plants commonly used to treat "stomach ailments" in Brazil: Schinus terebinthifolius Raddi (S) and Myracrodruon urundeuva Allemão (M). In male rats, chronic treatment (83 days) with both pepper trees (17.6 and 13.8 mg/kg, S and M, respectively) has been shown to decrease hematocrit. However, a reduction in the number of red blood cells and hemoglobin was only seen following administration of S. terebinthifolius. None of the plants caused anatomopathological alterations following chronic treatment, and mating ability and fertility were not affected. Both pepper trees showed moderate toxicity following acute and chronic treatment by gavage, particularly S. terebinthifolius. Moreover, bone malformations were induced in fetuses, and a slight delay in recovery time of the postural reflex was observed in pups from female animals treated (18 days) with S. terebinthifolius. Given these results, a better assessment of the risks and benefits of the internal use of these plants is necessary, especially when used by women of childbearing age. Copyright © 2012 John Wiley & Sons, Ltd.

Malingering in Toxic Exposure. Classification Accuracy of Reliable Digit Span and WAIS-III Digit Span Scaled Scores

ERIC Educational Resources Information Center

Greve, Kevin W.; Springer, Steven; Bianchini, Kevin J.; Black, F. William; Heinly, Matthew T.; Love, Jeffrey M.; Swift, Douglas A.; Ciota, Megan A.

2007-01-01

This study examined the sensitivity and false-positive error rate of reliable digit span (RDS) and the WAIS-III Digit Span (DS) scaled score in persons alleging toxic exposure and determined whether error rates differed from published rates in traumatic brain injury (TBI) and chronic pain (CP). Data were obtained from the files of 123 persons…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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-throughmore » 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.« less

Medicinal plants and natural products in amelioration of arsenic toxicity: a short review.

PubMed

Bhattacharya, Sanjib

2017-12-01

Chronic arsenic toxicity (arsenicosis) is considered a serious public health menace worldwide, as there is no specific, safe, and efficacious therapeutic management of arsenicosis. To collate the studies on medicinal plants and natural products with arsenic toxicity ameliorative effect, active pre-clinically and/or clinically. Literature survey was carried out by using Google, Scholar Google and Pub-Med. Only the scientific journal articles found on the internet for last two decades were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 34 medicinal plants and 14 natural products exhibited significant protection from arsenic toxicity, mostly in preclinical trials and a few in clinical studies. This research could lead to development of a potentially useful agent in clinical management of arsenicosis in humans.

A novel bioassay using the barnacle Amphibalanus amphitrite to evaluate chronic effects of aluminium, gallium and molybdenum in tropical marine receiving environments.

PubMed

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

2016-11-15

A need exists for appropriate tools to evaluate risk and monitor potential effects of contaminants in tropical marine environments, as currently impact assessments are conducted by non-representative approaches. Here, a novel bioassay is presented that allows for the estimation of the chronic toxicity of contaminants in receiving tropical marine environments. The bioassay is conducted using planktonic larvae of the barnacle Amphibalanus amphitrite and is targeted at generating environmentally relevant, chronic toxicity data for water quality guideline derivation or compliance testing. The developmental endpoint demonstrated a consistently high control performance, validated through the use of copper as a reference toxicant. In addition, the biological effects of aluminium, gallium and molybdenum were assessed. The endpoint expressed high sensitivity to copper and moderate sensitivity to aluminium, whereas gallium and molybdenum exhibited no discernible effects, even at high concentrations, providing valuable information on the toxicity of these elements in tropical marine waters. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

DTIC Science & Technology

2014-11-01

ORIGINAL CONTRIBUTION Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant...and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in...Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled

Studies on toxicity of OTEC plant components on marine animals from the Gulf of Mexico. Annual report for period October 1979-September 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkataramiah, A.; Lakshmi, G.J.; Best, C.

1981-06-01

This project was undertaken as a part of the OTEC environmental studies plan on the toxicity of OTEC working fluids to marine organisms. Ammonia and chlorine were chosen 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 fucorum) and filefish (Monocanthus hispidus).

IMATINIB 800MG DAILY INDUCES DEEPER MOLECULAR RESPONSES THAN IMATINIB 400MG DAILY: RESULTS OF SWOG S0325, AN INTERGROUP RANDOMIZED PHASE II TRIAL IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA

PubMed Central

Deininger, Michael W.; Kopecky, Kenneth J.; Radich, Jerald P.; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D.; Tallman, Martin; Wadleigh, Martha; Larson, Richard A.; Lipton, Jeffrey H.; Slovak, Marilyn L.; Appelbaum, Frederick R.; Druker, Brian J.

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukemia (CP-CML) is 400mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematologic and cytogenetic response to IM400 vs. imatinib 400mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P=0.038; 3-log reduction: 53% vs. 35%, P=0.049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2.9-fold lower than in the IM400 arm (P=0.010). Complete haematologic response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P=0.040). Grade 3–4 toxicities were more common for IM800 (58% vs. 31%, P=0.0007), and were most commonly haematologic. Few patients have relapsed, progressed or died, but progression-free (P=0.048) and relapse-free (P=0.031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper molecular responses than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. PMID:24383843

Effects of short- and long-term exposures to copper on lethal and reproductive endpoints of the harpacticoid copepod Tigriopus fulvus.

PubMed

Biandolino, Francesca; Parlapiano, Isabella; Faraponova, Olga; Prato, Ermelinda

2018-01-01

The long-term exposure provides a realistic measurement of the effects of toxicants on aquatic organisms. The harpacticoid copepod Tigriopus fulvus has a wide geographical distribution and is considered as an ideal model organism for ecotoxicological studies for its good sensitivity to different toxicants. In this study, acute, sub-chronic and chronic toxicity tests based on lethal and reproductive responses of Tigriopus fulvus to copper were performed. The number of moults during larval development was chosen as an endpoint for sub-chronic test. Sex ratio, inhibitory effect on larval development, hatching time, fecundity, brood number, nauplii/brood, total newborn production, etc, were calculated in the chronic test (28d). Lethal effect of copper to nauplii showed the LC50-48h of 310 ± 72µgCu/L (mean ± sd). It was observed a significant inhibition of larval development at sublethal copper concentrations, after 4 and 7 d. After 4d, the EC50 value obtained for the endpoint in "moult naupliar reduction" was of 55.8 ± 2.5µgCu/L (mean ± sd). The EC50 for the inhibition of naupliar development into copepodite stage, was of 21.7 ± 4.4µgCu/L (mean ± sd), after 7 days. Among the different traits tested, copper did not affect sex ratio and growth, while fecundity and total nauplii production were the most sensitive endpoints. The reproductive endpoints offer the advantage of being detectable at very low pollutant concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity of carbon nanotubes: A review.

PubMed

Francis, Arul Prakash; Devasena, Thiyagarajan

2018-03-01

Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

Paracetamol, alcohol and the liver

PubMed Central

Prescott, Laurie F

2000-01-01

It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

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 be exercised with its long-term usage. PMID:24795634

Evaluation of surface water quality using an ecotoxicological approach: a case study of the Alqueva Reservoir (Portugal).

PubMed

Palma, Patrícia; Alvarenga, Paula; Palma, Vera; Matos, Cláudia; Fernandes, Rosa Maria; Soares, Amadeu; Barbosa, Isabel Rita

2010-03-01

Freshwater reservoirs can be impacted by several hazardous substances through inputs from agricultural activity, sewage discharges, and groundwater leaching and runoff. The water quality assessment is very important for implementation of the monitoring and remediation programs to minimize the risk promoted by hazardous substances in aquatic ecosystems. Evaluation of the degree of contamination of aquatic environments must not take in account only its chemical characterization but it must be complemented with biological assays, which determine potential toxic effects and allows an integrated evaluation of its effects in populations and aquatic ecosystem communities. The application of this type of strategy has clear advantages allowing a general evaluation of the effects from all the water components, including those due to unknown substances and synergic, antagonistic, or additive effects. There are only a few studies that reported ecotoxicological acute end points, for the assessment of surface water quality, and the relationship among toxicity results and the anthropogenic pollution sources and the seasonal period. The aim of this study was to assess the ecotoxicological characterization of the surface water from Alqueva reservoir (South of Portugal) and to evaluate the influence of anthropogenic sources of pollution and their seasonal variation in its toxicity. The construction of Alqueva reservoir was recently finished (2002) and, to our knowledge, an ecotoxicological assessment of its surface water has not been performed. Because of that, no information is available on the possible impact of pollutants on the biota. The surface water toxicity was assessed using acute and chronic bioassays. The results are to be used for developing a monitoring program, including biological methods. Water samples were collected during 2006-2007, at each of the nine sampling sites selected in Alqueva reservoir. These sampling points allow an assessment at the upstream (Sra. Ajuda, Alcarrache, Alamos-Captação), at the middle (Alqueva-Montante, Alqueva-Mourão, Lucefecit), and at the downstream of the water line (Alqueva-Jusante; Ardila-confluência; Moinho das Barcas). The campaigns occurred in February, March, May, July, September, and November of 2006 and February, March, and May of 2007. The rainy season comprised November, February, and March, and the dry season included May, July, and September. A total of 81 samples were collected during the study period. The physical-chemical parameters were analyzed following standard and recommended methods of analysis (APHA et al. 1998). The pesticide analyses were performed using gas chromatography according to DIN EN ISO 6468 (1996). Surface water ecotoxicity was evaluated using the following bioassays: Vibrio fischeri luminescence inhibition, Thamnocephalus platyurus mortality, and Daphnia magna immobilization and reproduction assay. The Spearman rank correlation coefficients were used to evaluate the associations between the water sample physicochemical properties (from each sampling station in each season) and the acute and chronic toxicological effects, with a level of significance p < 0.05. In the acute toxicity study, the species that was found to be the most sensitive was T. platyurus. T. platyurus detected a higher number of toxic water samples during the dry season. Concerning the luminescent inhibition of V. fischeri, the results showed that this organism detected a great number of toxic water samples in rainy seasons. The water samples, which promoted higher toxic effects towards this species, were from the north and from the middle of the reservoir. The correlation analysis showed that V. fischeri luminescent inhibition (%) was positively correlated with total phosphorus, chlorpyrifos, iron, and arsenic. T. platyurus mortality (%) was positively correlated with the water pH, 5-day biochemical oxygen demand (BOD(5)), chlorides, atrazine, simazine, terbuthylazine, and endosulfan sulfate contents. Although the surface waters did not promote acute toxicity to the crustacean D. magna, in the chronic exposure, a significant decrease in the number of juveniles per female was observed, mainly at the dry period. The number of juveniles per female, in the reproduction test of D. magna, was negatively correlated with pH, temperature, BOD(5), chloride, atrazine, simazine, terbuthylazine, and endosulfan sulfate. The water toxicity of the Alqueva water might be due principally to the intensive agriculture activities surrounding the reservoir and to the municipal wastewater discharges. The physicochemical parameters and the pesticide concentrations indicated that the water quality was worse in the north part of the reservoir system. These results are characteristic of the majority of reservoirs, once the construction of the dam promoted, by itself, the impounding of water flow and the increase of compound residence time. The toxicity tests corroborate with the chemical characterization. Acute toxicity of Alqueva water may be a result of the effect promoted by chlorpyrifos, endosulfan sulfate, phosphorus, and iron. Chronic toxicity may be a result of the effect of herbicides, arsenic, organic matter, endosulfan sulfate in mixture. Hence, the water toxicity of the Alqueva might be due principally to the intensive agriculture activities surrounding the reservoir and to the municipal wastewater discharges. This study has shown that a large number of samples from different sites of the Alqueva reservoir contained potentially toxic contaminants. The sites with impaired water quality were those located at the north of the reservoir and in the surrounding areas of intensive agricultural activity. The results demonstrated that the use of a screening of acute and chronic toxicity tests with organisms from different trophic levels and with distinct sensibilities allowed the detections of several patterns of toxicity from spatial and temporal variability promoted by natural or anthropogenic sources. The chronic responses showed, especially in the dry season, that some of the species belonging to this aquatic ecosystem might be at risk. The V. fischeri and T. platyurus are two species that should be used in the acute bioassays for the ecotoxicological monitoring programs of this reservoir. It is recommended that other species, such as a productive organism (algae), be included in the next study, once the water reservoir had high levels of herbicides. Ecotoxicological assessment of surface water must integrate initial screening based on acute tests followed always by chronic bioassays. The results implicitly suggest that the implementation of processes of remediation by reducing pollutant input into the reservoir and by the implementation of water treatment processes is important and necessary.

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

PubMed

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

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox.

PubMed

Liu, Qianying; Lei, Zhixin; Huang, Anxiong; Wu, Qinghua; Xie, Shuyu; Awais, Ihsan; Dai, Menghong; Wang, Xu; Yuan, Zonghui

2017-02-03

Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver. Moreover, using LC/MS-ITTOF analysis, two metabolites of MEQ were detected in the liver, which directly confirms the potential connection between N → O group reduction metabolism of MEQ and liver toxicity. The gender difference in MEQ-induced oxidative stress might be due to adrenal toxicity and the generation of M4 (2-isoethanol 1-desoxymequindox). Furthermore, up-regulation of the MAPK and Nrf2-Keap1 family and phase II detoxifying enzymes (HO-1, GCLC and NQO1) were also observed. The present study demonstrated for the first time the protein peroxidation and a proposal metabolic pathway after chronic exposure of MEQ, and illustrated that the MAPK, Nrf2-Keap1 and NF-кB signaling pathways, as well as the altered metabolism of MEQ, were involved in oxidative toxicity mediated by MEQ in vivo.

Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox

PubMed Central

Liu, Qianying; Lei, Zhixin; Huang, Anxiong; Wu, Qinghua; Xie, Shuyu; Awais, Ihsan; Dai, Menghong; Wang, Xu; Yuan, Zonghui

2017-01-01

Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, and whether the metabolic pathway of MEQ is altered in response to the pathophysiological conditions still remain unclear. We now provide evidence that MEQ triggers oxidative damage in the liver. Moreover, using LC/MS-ITTOF analysis, two metabolites of MEQ were detected in the liver, which directly confirms the potential connection between N → O group reduction metabolism of MEQ and liver toxicity. The gender difference in MEQ-induced oxidative stress might be due to adrenal toxicity and the generation of M4 (2-isoethanol 1-desoxymequindox). Furthermore, up-regulation of the MAPK and Nrf2-Keap1 family and phase II detoxifying enzymes (HO-1, GCLC and NQO1) were also observed. The present study demonstrated for the first time the protein peroxidation and a proposal metabolic pathway after chronic exposure of MEQ, and illustrated that the MAPK, Nrf2-Keap1 and NF-кB signaling pathways, as well as the altered metabolism of MEQ, were involved in oxidative toxicity mediated by MEQ in vivo. PMID:28157180

Toxicological and chemical assessment of arsenic-contaminated groundwater after electrochemical and advanced oxidation treatments.

PubMed

Radić, Sandra; Crnojević, Helena; Vujčić, Valerija; Gajski, Goran; Gerić, Marko; Cvetković, Želimira; Petra, Cvjetko; Garaj-Vrhovac, Vera; Oreščanin, Višnja

2016-02-01

Owing to its proven toxicity and mutagenicity, arsenic is regarded a principal pollutant in water used for drinking. The objective of this study was the toxicological and chemical evaluation of groundwater samples obtained from arsenic enriched drinking water wells before and after electrochemical and ozone-UV-H2O2-based advanced oxidation processes (EAOP). For this purpose, acute toxicity test with Daphnia magna and chronic toxicity test with Lemna minor L. were employed as well as in vitro bioassays using human peripheral blood lymphocytes (HPBLs). Several oxidative stress parameters were estimated in L.minor. Physicochemical analysis showed that EAOP treatment was highly efficient in arsenic but also in ammonia and organic compound removal from contaminated groundwater. Untreated groundwater caused only slight toxicity to HPBLs and D. magna in acute experiments. However, 7-day exposure of L. minor to raw groundwater elicited genotoxicity, a significant growth inhibition and oxidative stress injury. The observed genotoxicity and toxicity of raw groundwater samples was almost completely eliminated by EAOP treatment. Generally, the results obtained with L. minor were in agreement with those obtained in the chemical analysis suggesting the sensitivity of the model organism in monitoring of arsenic-contaminated groundwater. In parallel to chemical analysis, the implementation of chronic toxicity bioassays in a battery is recommended in the assessment of the toxic and genotoxic potential of such complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-to-death approach to reveal chronic and cumulative toxicity of a fungicide for honeybees not revealed with the standard ten-day test.

PubMed

Simon-Delso, Noa; San Martin, Gilles; Bruneau, Etienne; Hautier, Louis

2018-05-08

Synthetic fungicides are pesticides widely used in agriculture to control phytopathogenic fungi. The systemicity, persistency and intense application of some of these fungicides, such as boscalid, leads to long periods of exposure for honeybees via contaminated water, pollen and nectar. We exposed adult honeybees in the lab to food contaminated with boscalid for 33 days instead of the standard 10-day test. Most of the toxic effects were observed after 10 days. The median time to death (LT 50 ) ranged from 24.9 days (lowest concentration) to 7.1 days (highest concentration) and was significantly shorter in all cases than with the control (32.0 days). The concentration and dietary doses of boscalid inducing 50% mortality (LC 50 and LDD 50 , respectively) decreased strongly with the time of exposure: LC 50  = 14,729 and 1,174 mg/l and LDD 50  = 0.318 and 0.0301 mg bee -1 day -1 at days 8 and 25, respectively. We found evidence of reinforced toxicity when exposure is prolonged, but with an unusual pattern: no cumulative toxicity is observed until 17-18 days, when a point of inflexion appears that suggests a reduced capacity of bees to deal with the toxicant. Our results show the importance of time-to-death experiments rather than fixed-duration studies for evaluating chronic toxicity.

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

PubMed

Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

2015-09-01

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

Toxic effects of chemical dispersant Corexit 9500 on water flea Daphnia magna.

PubMed

Toyota, Kenji; McNabb, Nicole A; Spyropoulos, Demetri D; Iguchi, Taisen; Kohno, Satomi

2017-02-01

In 2010, approximately 2.1 million gallons of chemical dispersants, mainly Corexit 9500, were applied in the Gulf of Mexico to prevent the oil slick from reaching shorelines and to accelerate biodegradation of oil during the Deepwater Horizon oil spill. Recent studies have revealed toxic effects of Corexit 9500 on marine microzooplankton that play important roles in food chains in marine ecosystems. However, there is still little known about the toxic effects of Corexit 9500 on freshwater zooplankton, even though oil spills do occur in freshwater and chemical dispersants may be used in response to these spills. The cladoceran crustacean, water flea Daphnia magna, is a well-established model species for various toxicological tests, including detection of juvenile hormone-like activity in test compounds. In this study, we conducted laboratory experiments to investigate the acute and chronic toxicity of Corexit 9500 using D. magna. The acute toxicity test was conducted according to OECD TG202 and the 48 h EC 50 was 1.31 ppm (CIs 0.99-1.64 ppm). The reproductive chronic toxicity test was performed following OECD TG211 ANNEX 7 and 21 days LOEC and NOEC values were 4.0 and 2.0 ppm, respectively. These results indicate that Corexit 9500 has toxic effects on daphnids, particularly during the neonatal developmental stage, which is consistent with marine zooplankton results, whereas juvenile hormone-like activity was not identified. Therefore, our findings of the adverse effects of Corexit 9500 on daphnids suggest that application of this type of chemical dispersant may have catastrophic impacts on freshwater ecosystems by disrupting the key food chain network. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Chronic arsenic intoxication diagnostic score (CAsIDS).

PubMed

Dani, Sergio Ulhoa; Walter, Gerhard Franz

2018-01-01

Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Overview of ToxCast™ | Science Inventory | US EPA

EPA Pesticide Factsheets

In 2007, EPA launched ToxCast™ in order to develop a cost-effective approach for prioritizing the toxicity testing of large numbers of chemicals in a short period of time. Using data from state-of-the-art high throughput screening (HTS) bioassays developed in the pharmaceutical industry, ToxCast™ is building computational models to forecast the potential human toxicity of chemicals. These hazard predictions will provide EPA regulatory programs with science-based information helpful in prioritizing chemicals for more detailed toxicological evaluations, and lead to more efficient use of animal testing. In its first phase, ToxCast™ is profiling over 300 well-characterized chemicals (primarily pesticides) in over 400 HTS endpoints. These endpoints include biochemical assays of protein function, cell-based transcriptional reporter assays, multi-cell interaction assays, transcriptomics on primary cell cultures, and developmental assays in zebrafish embryos. Almost all of the compounds being examined in Phase 1 of ToxCast™ have been tested in traditional toxicology tests, including developmental toxicity, multi-generation studies, and sub-chronic and chronic rodent bioassays. ToxRefDB, a relational database being created to house this information, will contain nearly $1B worth of toxicity studies in animals when completed. ToxRefDB is integrated into a more comprehensive data management system developed by NCCT called ACToR (Aggregated Computational Toxicology

Comparative toxicity of pristine graphene oxide and its carboxyl, imidazole or polyethylene glycol functionalized products to Daphnia magna: A two generation study.

PubMed

Liu, Yingying; Han, Wenli; Xu, Zhizhen; Fan, Wenhong; Peng, Weihua; Luo, Shenglian

2018-06-01

To investigate the chronic toxicity of graphene oxide (GO) and its functionalized products (GO-carboxyl, GO-imidazole and GO-polyethylene glycol), a two-generation study was conducted using the aquatic model species Daphnia magna. Each generation of daphnids were exposed for 21 days to 1.0 mg L -1 graphene material, with body length, neonate number, time of first brood and the intrinsic rate of natural increase (r) assessed as endpoints. Chronic exposure to GO, GO-carboxyl, and GO-imidazole had no adverse effect on body length or offspring number in the daphnid F0 generation, however, this exposure paradigm led to significant growth or reproduction inhibition in the following generation. Meanwhile, GO was found to show the strongest inhibitory effect, sequentially followed by GO-carboxyl and GO-imidazole. With exposure to GO-polyethylene glycol, no significant effects on growth or reproduction were observed for both F0 and F1 generation daphnids. These results reveal that carboxyl, imidazole and polyethylene glycol functional attachments alleviate the bio-toxicity of GO, especially polyethylene glycol. The increased C/O atomic ratio present in GO-carboxyl, GO-imidazole and GO-polyethylene glycol due to functionalization may mainly explain the reduced toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling

EPA Pesticide Factsheets

Researchers facilitated evaluation of chemicals that lack chronic oral toxicity values using a QSAR model to develop estimates of potential toxicity for chemicals used in HF fluids or found in flowback or produced water

Assessing the toxicity and risk of salt-impacted winter road runoff to the early life stages of freshwater mussels in the Canadian province of Ontario.

PubMed

Prosser, R S; Rochfort, Q; McInnis, R; Exall, K; Gillis, P L

2017-11-01

In temperate urbanized areas where road salting is used for winter road maintenance, the level of chloride in surface waters has been increasing. While a number of studies have shown that the early-life stages of freshwater mussels are particularly sensitive to salt; few studies have examined the toxicity of salt-impacted winter road runoff to the early-life stages of freshwater mussels to confirm that chloride is the driver of toxicity in this mixture. This study examines the acute toxicity of field-collected winter road runoff to the glochidia of wavy-rayed lampmussels (Lampsilis fasciola) (48 h exposure) and newly released juvenile fatmucket mussels (Lampsilis siliquoidea) (<1 week old; 96 h exposure) under different water hardness. The chronic toxicity (28 d) to older juvenile L. siliquoidea (7-12 months old) was also investigated. The 48-h EC50 and 96-h LC50 for L. fasciola glochidia and L. siliquoidea juveniles exposed to different dilutions of road run-off created with moderately hard synthetic water (∼80 mg CaCO 3 /L) were 1177 (95% confidence interval (CI): 1011-1344 mg Cl - /L) and 2276 mg Cl - /L (95% CI: 1698-2854 mg Cl - /L), respectively. These effect concentrations correspond with the toxicity of chloride reported in other studies, indicating that chloride is likely the driver of toxicity in salt-impacted road-runoff, with other contaminants (e.g., metals, polycyclic aromatic hydrocarbons) playing a de minimis role. Toxicity data from the current study and literature and concentrations of chloride in the surface waters of Ontario were used to conduct a probabilistic risk assessment of chloride to early-life stage freshwater mussels. The assessment indicated that chronic exposure to elevated chloride levels could pose a risk to freshwater mussels; further investigation is warranted to ensure that the most sensitive organisms are protected. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

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

Deriving freshwater safety thresholds for hexabromocyclododecane and comparison of toxicity of brominated flame retardants.

PubMed

Dong, Liang; Zheng, Lei; Yang, Suwen; Yan, Zhenguang; Jin, Weidong; Yan, Yuhong

2017-05-01

Hexabromocyclododecane (HBCD) is a brominated flame retardant used throughout the world. It has been detected in various environmental media and has been shown toxic to aquatic life. The toxic effects of HBCD to aquatic organisms in Chinese freshwater ecosystems are discussed here. Experiments were conducted with nine types of acute toxicity testing and three types of chronic toxicity testing. After comparing a range of species sensitivity distribution models, the optimal model of Bull III was used to derive the safety thresholds for HBCD. The acute safety threshold and the chronic safety threshold of HBCD for Chinese freshwater organisms were found to be 2.32mg/L and 0.128mg/L, respectively. Both values were verified by the methods of the Netherlands and the United States. HBCD was found to be less toxic compared to other widely used brominated flame retardants. The present results provide valuable information for revision of the water quality standard of HBCD in China. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Selenium and Human Health: Witnessing a Copernican Revolution?

PubMed

Jablonska, Ewa; Vinceti, Marco

2015-01-01

In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

Sunlight-induced degradation of fluoroquinolones in wastewater effluent: Photoproducts identification and toxicity.

PubMed

Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Ferri, Elida Nora; Profumo, Antonella

2015-09-01

The photodegradation of Ciprofloxacin (CIP), Enrofloxacin (ENR), Danofloxacin (DAN), Marbofloxacin (MAR) and Levofloxacin (LEV), five widely used fluoroquinolones (FQs), was studied in urban WWTP secondary effluent, under solar light. The degradation profiles and the kinetic constants were determined at the micrograms per litre levels (20-50 μg L(-1)). The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The toxicity of the photoproducts was assessed by Vibrio fischeri light emission inhibition assay performed on irradiated and not-irradiated FQs solutions, at environmentally significant concentrations. Attention was focused on the evaluation of the photoproducts contribution to the overall biotoxic effect of these emerging pollutants. Data from chronic exposure experiments (24-48 h) were primarily considered. Results confirmed the major usefulness of chronic toxicity data with respect to the acute assay ones and proved the not negligible biotoxicity of the FQs photodegradation products. Copyright © 2015 Elsevier Ltd. All rights reserved.

What's Out There Making Us Sick?

PubMed Central

Genuis, Stephen J.

2012-01-01

Throughout the continuum of medical and scientific history, repeated evidence has confirmed that the main etiological determinants of disease are nutritional deficiency, toxicant exposures, genetic predisposition, infectious agents, and psychological dysfunction. Contemporary conventional medicine generally operates within a genetic predestination paradigm, attributing most chronic and degenerative illness to genomic factors, while incorporating pathogens and psychological disorder in specific situations. Toxicity and deficiency states often receive insufficient attention as common source causes of chronic disease in the developed world. Recent scientific evidence in health disciplines including molecular medicine, epigenetics, and environmental health sciences, however, reveal ineluctable evidence that deficiency and toxicity states feature prominently as common etiological determinants of contemporary ill-health. Incorporating evidence from historical and emerging science, it is evident that a reevaluation of conventional wisdom on the current construct of disease origins should be considered and that new knowledge should receive expeditious translation into clinical strategies for disease management and health promotion. An analysis of almost any scientific problem leads automatically to a study of its history.—Ernst Mayr PMID:22262979

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish).

PubMed

Watanabe, Haruna; Tamura, Ikumi; Abe, Ryoko; Takanobu, Hitomi; Nakamura, Ataru; Suzuki, Toshinari; Hirose, Akihiko; Nishimura, Tetsuji; Tatarazako, Norihisa

2016-04-01

Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action. © 2015 SETAC.

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

PubMed Central

Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

PubMed

Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

2017-01-01

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

Toxicity of ammonia to three marine fish and three marine invertebrates.

PubMed

Boardman, Gregory D; Starbuck, Steven M; Hudgins, Douglas B; Li, Xiayoun; Kuhn, David D

2004-04-01

Laboratory toxicity tests were performed to obtain more data on the toxicity of ammonia to saltwater organisms. The standards for in-stream ammonia limits in marine environments presently are based on toxicity tests involving both freshwater and saltwater organisms. Acute tests (48 and 96 h) were performed at 20 degrees C, and chronic tests (7 days) were performed at 25 degrees C. Synthetic seawater and natural seawater from the Chesapeake Bay were used and compared. Included among the organisms tested were sheepshead minnow (14 days old), summer flounder (2 months old), Atlantic silverside (14 days old), mysid shrimp (less than 2 days old), ghost shrimp (10 days old), and quahog clam (9 months old). Based on these results, it seems the chronic criterion for ammonia in marine environments could be increased from 0.035 to 0.081 mg/L un-ionized ammonia, which would, of course, increase the chronic limit for total ammonia under typical saltwater conditions by a factor of 2.31. No difference was observed in the toxicity of ammonia in natural water compared to synthetic water for both the summer flounder and Atlantic silverside. Furthermore, the Atlantic silverside became more sensitive to ammonia as the salinity was increased from 14 to 22 ppt, but exhibited no change in toxicity response from 22 to 30 ppt. Copyright 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 134-142, 2004

Ecological impacts of lead mining on Ozark streams: toxicity of sediment and pore water.

PubMed

Besser, John M; Brumbaugh, William G; Allert, Ann L; Poulton, Barry C; Schmitt, Christopher J; Ingersoll, Christopher G

2009-02-01

We studied the toxicity of sediments downstream of lead-zinc mining areas in southeast Missouri, using chronic sediment toxicity tests with the amphipod, Hyalella azteca, and pore-water toxicity tests with the daphnid, Ceriodaphnia dubia. Tests conducted in 2002 documented reduced survival of amphipods in stream sediments collected near mining areas and reduced survival and reproduction of daphnids in most pore waters tested. Additional amphipod tests conducted in 2004 documented significant toxic effects of sediments from three streams downstream of mining areas: Strother Creek, West Fork Black River, and Bee Fork. Greatest toxicity occurred in sediments from a 6-km reach of upper Strother Creek, but significant toxic effects occurred in sediments collected at least 14 km downstream of mining in all three watersheds. Toxic effects were significantly correlated with metal concentrations (nickel, zinc, cadmium, and lead) in sediments and pore waters and were generally consistent with predictions of metal toxicity risks based on sediment quality guidelines, although ammonia and manganese may also have contributed to toxicity at a few sites. Responses of amphipods in sediment toxicity tests were significantly correlated with characteristics of benthic invertebrate communities in study streams. These results indicate that toxicity of metals associated with sediments contributes to adverse ecological effects in streams draining the Viburnum Trend mining district.

Ecological impacts of lead mining on Ozark streams: Toxicity of sediment and pore water

USGS Publications Warehouse

Besser, J.M.; Brumbaugh, W.G.; Allert, A.L.; Poulton, B.C.; Schmitt, C.J.; Ingersoll, C.G.

2009-01-01

We studied the toxicity of sediments downstream of lead-zinc mining areas in southeast Missouri, using chronic sediment toxicity tests with the amphipod, Hyalella azteca, and pore-water toxicity tests with the daphnid, Ceriodaphnia dubia. Tests conducted in 2002 documented reduced survival of amphipods in stream sediments collected near mining areas and reduced survival and reproduction of daphnids in most pore waters tested. Additional amphipod tests conducted in 2004 documented significant toxic effects of sediments from three streams downstream of mining areas: Strother Creek, West Fork Black River, and Bee Fork. Greatest toxicity occurred in sediments from a 6-km reach of upper Strother Creek, but significant toxic effects occurred in sediments collected at least 14 km downstream of mining in all three watersheds. Toxic effects were significantly correlated with metal concentrations (nickel, zinc, cadmium, and lead) in sediments and pore waters and were generally consistent with predictions of metal toxicity risks based on sediment quality guidelines, although ammonia and manganese may also have contributed to toxicity at a few sites. Responses of amphipods in sediment toxicity tests were significantly correlated with characteristics of benthic invertebrate communities in study streams. These results indicate that toxicity of metals associated with sediments contributes to adverse ecological effects in streams draining the Viburnum Trend mining district.

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 2007). 2. Acute Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae...). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2... (Reapproved 2007). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity...

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 2007). 2. Acute Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae...). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2... (Reapproved 2007). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity...

Toxicity of ferric chloride sludge to aquatic organisms.

PubMed

Sotero-Santos, Rosana B; Rocha, Odete; Povinelli, Jurandyr

2007-06-01

Iron-rich sludge from a drinking water treatment plant (DWTP) was investigated regarding its toxicity to aquatic organisms and physical and chemical composition. In addition, the water quality of the receiving stream near the DWTP was evaluated. Experiments were carried out in August 1998, February 1999 and May 1999. Acute toxicity tests were carried out on a cladoceran (Daphnia similis), a midge (Chironomus xanthus) and a fish (Hyphessobrycon eques). Chronic tests were conducted only on D. similis. Acute sludge toxicity was not detected using any of the aquatic organisms, but chronic effects were observed upon the fecundity of D. similis. Although there were relatively few sample dates, the results suggested that the DWTP sludge had a negative effect on the receiving body as here was increased suspended matter, turbidity, conductivity, chemical oxygen demand (COD) and hardness in the water downstream of the DWTP effluent discharge. The ferric chloride sludge also exhibited high heavy metal concentrations revealing a further potential for pollution and harmful chronic effects on the aquatic biota when the sludge is disposed of without previous treatment.

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

PubMed

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

2013-01-01

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

Ginkgo biloba leaf extract action in scavenging free radicals and reducing mutagenicity and toxicity of cigarette smoke in vivo.

PubMed

Wang, Chang G; Dai, Ya; Li, Dong L; Ma, Kuo Y

2010-01-01

In this study, ginkgo biloba leaf extract (GBE) was added to sample cigarettes, including in the filter (0.8 mg/cigarette) and/or the cut filler (0.8 mg/cigarette). The effects of GBE in scavenging free radicals and reducing mutagenicity and toxicity of cigarette smoke in vivo were investigated. Smoke analysis results indicated that GBE eliminated up to 30% of free radicals. Biological experiments, conducted for both GBE cigarettes and control samples, included the Ames test, acute toxicity, neutral red cytotoxicity assay and chronic toxicity. Results showed that the mutagenicity and toxicity of the GBE cigarettes were lower than for the control cigarettes. A possible mechanism of GBE in scavenging free radicals is discussed in this article.

Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

PubMed

Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

2017-01-01

Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Health effects of groundwater fluoride contamination.

PubMed

Nayak, Bishwajit; Roy, Madan Mohan; Das, Bhaskar; Pal, Arup; Sengupta, Mrinal Kumar; De, Shankar Prasad; Chakraborti, Dipankar

2009-04-01

The people in Berhait block, Sahibganj district, Jharkhand state, India, have been exposed chronically to fluoridecontaminated groundwater. Hereby, we report the clinical effects of chronic exposure to fluoride. The study population was a convenience sample of 342 adults and 258 children living in the affected area. All volunteers filled out questionnaires and were examined. Well water from the six affected villages and urine samples were analyzed for fluoride using an ion-sensitive electrode. Twenty nine percent of 89 well water samples had fluoride concentrations above the Indian permissible limit of fluoride in drinking water. Eighty-five children and 72 adults had clinical fluorosis. Urine fluoride concentrations in children were 0.758-2.88 mg/L whereas in adults they were 0.331-10.36 mg/L. Clinical effects of fluoride included abnormal tooth enamel in children; adults had joint pain and deformity of the limbs and spine, along with ligamentous calcifications and exostosis formations in seven patients. Elevated urine fluoride concentrations supported the clinical diagnosis of fluorosis. Owing to insufficient fluoride-safe wells and lack of awareness of the danger of fluoride toxicity, villagers often drink fluoride-contaminated water. Villagers of Berhait block, including children, are at risk from chronic fluoride toxicity. To combat the situation, villagers need fluoride-safe water, education, and awareness of the danger about fluoride toxicity.

Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

PubMed Central

Mohammod Mostakim, Golam; Zahangir, Md. Mahiuddin; Monir Mishu, Mahbuba; Rahman, Md. Khalilur; Islam, M. Sadiqul

2015-01-01

Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p < 0.05) at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations. PMID:26635877

Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.

Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2more » h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people.« less

Acute and Chronic Toxicities of TNT and RDX to the Enchytraeid Worm, Enchytraeus crypticus, in Natural Soils

DTIC Science & Technology

2012-11-01

21010-5424 8. PERFORMING ORGANIZATION REPORT NUMBER ECBC-TR-981 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) Strategic Environmental ...triazine (RDX) to the potworm Enchytraeus crypticus using the Enchytraeid Reproduction Test (ISO 16387:2004). Studies were designed to identify and...clay loam soils. Toxicity benchmarks established in TSL and SSL will be submitted to the U.S. Environmental Protection Agency Eco-SSL Workgroup for

Modulation of GSH with exogenous agents leads to changes in glyoxalase 1 enzyme activity in VL-17A cells exposed to chronic alcohol plus high glucose.

PubMed

Kumar, S Mathan; Swaminathan, Kavitha; Clemens, Dahn L; Dey, Aparajita

2014-02-01

Gluthathione (GSH) is a major cellular antioxidant. The present study utilizing VL-17A cells exposed to chronic alcohol plus high glucose investigated the changes in oxidative stress, toxicity, and glyoxalase 1 activity as a detoxification pathway due to changes in GSH level through GSH supplementation with N-acetyl cysteine (NAC) or ursodeoxycholic acid (UDCA) and its depletion through buthionine sulfoximine (BSO) or diethyl maleate (DEM). Glyoxalase 1 plays an important role in detoxification of methylglyoxal which is formed as a precursor of advanced glycated end products formed due to high glucose mediated oxidative stress. Significant changes in glyoxalase 1 activity utilizing methylglyoxal or glyoxal as substrates occurred with NAC or UDCA or BSO or DEM supplementation in chronic alcohol plus high glucose treated VL-17A cells. NAC or UDCA administration in chronic alcohol plus high glucose treated VL-17A cells increased viability and decreased ROS levels, lipid peroxidation and 3-nitrotyrosine adduct formation. Similarly, GSH depletion with BSO or DEM had an opposite effect on the parameters in chronic alcohol plus high glucose treated VL-17A cells. In conclusion, modulation of GSH with NAC or UDCA or BSO or DEM leads to significant changes in oxidative stress, glyoxalase 1 enzyme activity and toxicity in chronic alcohol plus high glucose treated VL-17A cells.

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

2016-05-03

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.

TOXICITY COMPARISON OF BIOSURFACTANTS AND SYNTHETIC SURFACTANTS USED IN OIL SPILL REMEDIATION TO TWO ESTUARINE SPECIES

EPA Science Inventory

The relative environmental toxicities of synthetic and biogenic surfactants used in oil spill remediation efforts are not well understood. Acute and chronic toxicities of three synthetic surfactants and three microbially produced surfactants were determined and compared in this s...

Methods For Collecting , Culturing And Performing Toxicity Tests With Daphnia ambigua

DOE Office of Scientific and Technical Information (OSTI.GOV)

Specht, Winona L.

2005-07-01

Toxicity tests conducted on water collected from impacted locations in SRS streams often failed chronic toxicity tests and sometimes failed acute toxicity tests (Specht 1995). These findings prompted SRS to determine the cause of the failures. Some SRS NPDES outfalls were also failing chronic toxicity tests, even though no toxicant could be identified and when TIEs were performed, none of the TIE treatments removed the toxicity. Ultimately, it was determined that the failures were due to the low hardness of SRS surface waters, rather than to the presence of a toxicant. The species of cladoceran that the EPA recommends formore » toxicity testing, Ceriodaphnia dubia, is stressed by the very low hardness of SRS waters. SRS developed an alternate species toxicity test that is similar to the EPA test, but uses an indigenous cladoceran, Daphnia ambigua (Specht and Harmon, 1997; Harmon et al., 2003). In 2001, SCDHEC approved the use of D. ambigua for toxicity testing at SRS, contingent upon approval by EPA Region 4. In 2002, EPA Region 4 approved the use of this species for compliance toxicity testing at SRS. Ultimately, the use of this species demonstrated that SRS effluents were not toxic, and most toxicity testing requirements were removed from the NPDES permit that was issued in December 2003, with the exception of one round of chronic definitive testing on outfalls A-01, A-11, and G-10 just before the next NPDES permit application is submitted to SCDHEC. Although the alternate species test was developed at SRS (1996-1998), the culture was transferred to a contract toxicity testing lab (ETT Environmental) located in Greer, SC in 1998. ETT Environmental became certified by SCDHEC to perform toxicity tests using D. ambigua in 2002, and at this time is the only laboratory certified by SCDHEC to perform tests with this species. Because of the expense associated with maintaining the D. ambigua culture for several years when no toxicity testing is required, SRS decided to suspend financial support associated with maintaining the cultures until testing is needed. The purpose of this document is to provide guidance on how to establish a laboratory culture of D. ambigua so that a culture can be restarted when needed.« less

Imatinib 800 mg daily induces deeper molecular responses than imatinib 400 mg daily: results of SWOG S0325, an intergroup randomized PHASE II trial in newly diagnosed chronic phase chronic myeloid leukaemia.

PubMed

Deininger, Michael W; Kopecky, Kenneth J; Radich, Jerald P; Kamel-Reid, Suzanne; Stock, Wendy; Paietta, Elisabeth; Emanuel, Peter D; Tallman, Martin; Wadleigh, Martha; Larson, Richard A; Lipton, Jeffrey H; Slovak, Marilyn L; Appelbaum, Frederick R; Druker, Brian J

2014-01-01

The standard dose of imatinib for newly diagnosed patients with chronic phase chronic myeloid leukaemia (CP-CML) is 400 mg daily (IM400), but the optimal dose is unknown. This randomized phase II study compared the rates of molecular, haematological and cytogenetic response to IM400 vs. imatinib 400 mg twice daily (IM800) in 153 adult patients with CP-CML. Dose adjustments for toxicity were flexible to maximize retention on study. Molecular response (MR) at 12 months was deeper in the IM800 arm (4-log reduction of BCR-ABL1 mRNA: 25% vs. 10% of patients, P = 0·038; 3-log reduction: 53% vs. 35%, P = 0·049). During the first 12 months BCR-ABL1 levels in the IM800 arm were an average 2·9-fold lower than in the IM400 arm (P = 0·010). Complete haematological response was similar, but complete cytogenetic response was higher with IM800 (85% vs. 67%, P = 0·040). Grade 3-4 toxicities were more common for IM800 (58% vs. 31%, P = 0·0007), and were most commonly haematological. Few patients have relapsed, progressed or died, but both progression-free (P = 0·048) and relapse-free (P = 0·031) survival were superior for IM800. In newly diagnosed CP-CML patients, IM800 induced deeper MRs than IM400, with a trend for improved progression-free and overall survival, but was associated with more severe toxicity. © 2013 John Wiley & Sons Ltd.

Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the Fischer 344 Rat). Volume 1

DTIC Science & Technology

1984-12-01

the study were also analyzed for nitrate, nitrite and mercury content by TEl. 200 Fischer 344 rats, obtained from Harlan Sprague-Dawley, Madison , WI...Iles Pancreas Pituitary gland Prostate Rectum Salivary gland Sciatic nerve Seminal vesicles Skin, abdominal Spinal cord (cervical, thoracic, lumbar ...Skin, abdominal Spinal cord (cervical, thoracic and lumbar ) Sp I een Sternum Including bone marrow Stomach TIssue masses Thyroids (parathyrolds

Pathological Studies on the Protective Effect of a Macrolide Antibiotic, Roxithromycin, against Sulfur Mustard Inhalation Toxicity in a Rat Model

DTIC Science & Technology

2011-01-01

placed in a water-jacketed (37C) glass vapor generator custom fabri - cated by Atmar Glass (Kennett Square, PA). Spontaneously breathing rats were...bronchiectasis, and pul- monary fibrosis (Emad and Rezaian 1997). Macrolide antibio- tics have shown effectiveness in a variety of chronic respiratory diseases ...observed in clinical studies of chronic inflammatory airway diseases (e.g., DPB) after long-term treatment with low dose of macrolides (Rubin 2004). For

Division of Biological and Medical Research annual research summary, 1983

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barr, S.H.

1984-08-01

This research summary contains brief descriptions of research in the following areas: (1) mechanisms of hepatocarcinogenesis; (2) role of metals in cocarcinogenesis and the use of liposomes for metal mobilization; (3) control of mutagenesis and cell differentiation in cultured cells by tumor promoters; (4) radiation effects in mammalian cells; (5) radiation carcinogenesis and radioprotectors; (6) life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations; (7) mammalian genetics and biostatistics; (8) radiation toxicity studies; (9) hematopoiesis in chronic toxicity; (10) molecular biology studies; (11) chemical toxicology; (12) carcinogen identification and metabolism; (13) metal metabolism and toxicity; and (14)more » neurobehavioral chronobiology. (ACR)« less

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

PubMed

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

2014-06-01

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

Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

PubMed Central

Valenzuela, Olga L.; Borja-Aburto, Victor H.; Garcia-Vargas, Gonzalo G.; Cruz-Gonzalez, Martha B.; Garcia-Montalvo, Eliud A.; Calderon-Aranda, Emma S.; Del Razo, Luz M.

2005-01-01

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. PMID:15743710

Synthetic vitreous fibers: a review toxicology, epidemiology and regulations.

PubMed

Bernstein, David M

2007-01-01

This review addresses the characteristics which differentiate synthetic vitreous fibers (SVFs, e.g., fiber glass, stonewool, slagwool, refractory ceramic fibers, etc.), how these influence the potential biopersistence and toxicity, the most recent epidemiological results and the integration of these findings into the health and safety regulations in Europe and the United States. Also presented is the historical basis for the European classification directive. The use and equivalence of the chronic inhalation toxicology and chronic intraperitoneal injection studies in laboratory rodents for evaluation of fiber toxicology is assessed as well as the impact of dose selection and design on the validity of the study. While synthetic vitreous fibers can span a wide range of chemistries, recognition and understanding of the importance of biopersistence (ability to persist in the lung) in fiber toxicity has led to the development of more and more biosoluble fibers (that break down rapidly in the lung). Still, the epidemiological data available which are largely based upon the use of fibers in past decades, indicate that the SVF do not present a human health risk at current exposure levels. The animal toxicology and biopersistence data provide a coherent basis for understanding and evaluating the parameters which affect SVF toxicity. The current regulations are based upon an extensive knowledge base of chronic studies in laboratory rodents which confirm the relationship between chronic adverse effects and the biopersistence of the longer fibers that can not be fully phagocytised and efficiently cleared from the lung. The amorphous structure of synthetic vitreous fibers facilitates designing fibers in use today with low biopersistence. Both the epidemiological data and the animal studies database provide strong assurance that there is little if any health risk associated with the use of SVFs of low biopersistence. IARC (2001) reclassified these fibers from Category 2b to Category 3 (with RCF and special purpose fibers remaining in 2b) an event which has not been common in the history of these monographs.

Toxicity of Cold Lake Blend and Western Canadian Select dilbits to standard aquatic test species

EPA Science Inventory

Dilbits are blends of bitumen and natural gas condensates or crude oils with only limited toxicity data. Two dilbits, Cold Lake Blend and Western Canadian Select, were tested as either unweathered or weathered oils for acute and chronic toxicity to standard freshwater and estuari...

Integration of Density Dependence and Concentration Response Models Provides an Ecologically Relevant Assessment of Populations Exposed to Toxicants

EPA Science Inventory

The assessment of toxic exposure on wildlife populations involves the integration of organism level effects measured in toxicity tests (e.g., chronic life cycle) and population models. These modeling exercises typically ignore density dependence, primarily because information on ...

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...

Evaluation of the Polyethylene Reverse Sampler as a Dosing System in Marine Phase II Whole Sediment Toxicity Identification Evaluations (TIEs)

EPA Science Inventory

Contaminated marine sediments can cause acute and chronic impairments to benthic organisms. Nonionic organic contaminants (NOCs) are often a primary cause of impairment. Toxicity Identification Evaluations (TIEs) are used to identify chemicals causing toxicity in sediments. Ph...

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

PubMed

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

2012-11-01

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

An assessment of agricultural pesticide use in Iran, 2012-2014.

PubMed

Morteza, Zaim; Mousavi, Seyed Behzad; Baghestani, Mohammad Ali; Aitio, Antero

2017-01-01

This is the first published assessment on agricultural pesticide use in Iran with the aim to identify pesticide products with a potential of causing acute or chronic hazard to human health. It also establishes a baseline for future comparisons and for trend assessments. The amounts of imported technical materials for formulation by local manufacturers as well as imported final product formulations were extracted from the registration data of the Plant Protection Organization of Iran in 2012-2014. The hazard indicators used were acute oral toxicity and chronic toxicity. For the latter, carcinogenicity, mutagenicity, and adverse effects on reproduction or development (CMR toxicity), and low Acceptable Daily Intake (ADI) were used. The comparative potential of the active ingredients of concern in terms of chronic toxicity was assessed using the average annual volume of their estimated use divided by their respective ADI, called chronic hazard potential (CHP) in the present text. The contribution of individual pesticides in different use categories to the total CHP of the user category, was also calculated, using the average annual volume of the active ingredients of all pesticides used during the period 2012-2014. On average about 14,000 tonnes of agriculture pesticides, expressed in active ingredients (AI), were annually used in Iran. Herbicides constituted the largest volume (43%), followed by insecticides and acaricides (37%) and fungicides (19%). 0.1% and 47% of the formulated products met the criteria of WHO Class Ib (highly hazardous) and Class II (moderately hazardous) products respectively. Aluminium phosphide and magnesium phosphide were identified as products of primary concern and chlorpyrifos, diazinon and paraquat as products of secondary concern, in terms of their acute human health hazard. No compound in carcinogenicity category 1A or 1B or germ cell mutagenicity/reproduction toxicity category 1A was identified. Six compounds (diazinon, chlorpyrifos, dichlorvos, metam sodium, paraquat and dimethoate) were identified as products with chronic hazard potential based on a low ADI. The assessment identified and prioritized agriculture pesticide used in Iran in terms of their acute and chronic hazard to human health for re-registration scheme recently established by PPO and for risk mitigation. It also set priority for research into development of alternative products and practices to minimize pesticide risks. Chronic hazard potential - amount of use adjusted with toxicity may serve as a useful point of reference for trend analysis also in the use of less hazardous agricultural pesticide products.

The effect of probiotic bacteria (Lactobacillus acidophilus and Bifidobacterium lactis) on the accumulation of lead in rat brains.

PubMed

Zanjani, Saman Yahyavi; Eskandari, Mohammad Reza; Kamali, Koorosh; Mohseni, Mehran

2017-01-01

Lead is a toxic metal present in different concentrations in a wide variety of food products. Exposure to lead, even to low levels, causes acute and chronic toxicities. Lead can cross the blood-brain barrier and accumulate in the nervous system. Probiotics are live microorganisms that, when used in adequate amounts, confer a health benefit on the host. Although a recent study demonstrated that the studied bacteria have a protective effect against acute lead toxicity, no research has been found that shows the long-term impact of these bacteria in vivo. The current study surveyed the protective effects of two species of probiotics, Lactobacillus acidophilus LA-5 and Bifidobacterium lactis BB-12, that are most widely used in many functional foods against oral lead exposure (4 weeks) in rat brains. The results revealed that, at the end of the second week of chronic exposure to lead and probiotic bacteria, the lowest level of lead belonged to the Lactobacillus group. At the end of the fourth week, the lowest amount of lead was related to the group receiving both types of probiotics. With the physiological benefits of probiotic consumption, the bacterial solution in this study did not show high efficacy in reducing brain lead concentrations.

A fresh look at road salt: aquatic toxicity and water-quality impacts on local, regional, and national scales.

PubMed

Corsi, Steven R; Graczyk, David J; Geis, Steven W; Booth, Nathaniel L; Richards, Kevin D

2010-10-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30,800 μS/cm (Cl = 11,200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria.

Chronic Inhalation Toxicity of Hydrazine: Oncogenic Effects

DTIC Science & Technology

1981-06-01

AFAMRL-TR-81-56 CHRONIC INHALATION TOXICITY OF HYDRAZINE: ONCOGENIC EFFECTS J. D. MacEWEN E. H. VERNOT C C HAUN L . R. KINKEAD UNIVERSITY OF...Acknowledgement is made to A. K. Roychowdhury, Ph.D., J. D. Diaz, G. L . Fogle, Maj. R. Amster and J. A. Sizemore for their significant contributions and...Hemoglobin (g %) for Dogs Exposed to Hydrazine for One Year 49 24 Group Mean Values ± Standard Deviations of Sodium (mEq/ L ) for Dogs Exposed to

Chronic toxicity of arsenic during Rhinella arenarum embryonic and larval development: Potential biomarkers of oxidative stress and antioxidant response.

PubMed

Mardirosian, Mariana Noelia; Lascano, Cecilia Inés; Bongiovanni, Guillermina Azucena; Venturino, Andrés

2017-06-01

The Argentinean autochthonous toad Rhinella arenarum was selected to study the chronic toxicity of arsenic (As) and the biochemical responses elicited by exposure to As in water during embryonic and larval development. Significant decreases in the total reactive antioxidant potential and in catalase activity were observed in individuals exposed chronically to sublethal concentrations of As, which is indicative of an oxidative stress situation. However, an antioxidant response was elicited during chronic exposure to As, as evidenced by the increase in endogenous reduced glutathione content and glutathione-related enzymatic activities such as glutathione S-transferase (GST) and glutathione reductase. This protective response might prevent a deeper decline in the antioxidant system and further oxidative damage. Alternatively, it might be linked to As conjugation with reduced glutathione for its excretion. Considering the sustained increase in GST activity and the decrease in the total antioxidant reactive potential observed, the authors propose them as good candidates to be used as biomarkers during As exposure. Interestingly, glutathione reductase activity was inhibited at a very low concentration of As considered safe for aquatic life. Environ Toxicol Chem 2017;36:1614-1621. © 2016 SETAC. © 2016 SETAC.

Chronic preclinical safety evaluation of EPO-018B, a pegylated peptidic erythropoiesis-stimulating agent in monkeys and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Xue-Lian; Gu, Xiao-Lei

EPO-018B, a synthetic peptide-based erythropoiesis stimulating agent (ESA), is mainly designed for treatment of anemia caused by chronic renal failure and chemotherapy against cancer. It overcomes the deficiencies of currently approved ESA, including the frequent administration of temperature-sensitive recombinant protein and anti-EPO antibody-mediated pure red cell aplasia (PRCA). This study was designed to evaluate the potential chronic toxicity of EPO-018B. Subcutaneous administration doses were designed as 0, 0.2, 1 and 10 mg/kg for six months for 160 rats (20/gender/group) and 0, 0.3, 3 and 20 mg/kg for nine months for 32 monkeys (4/gender/group) once every three weeks. The vehicles receivedmore » the same volume of physiological saline injection. All animals survived to the scheduled necropsies after six weeks (for rats) and fourteen weeks (for monkeys) recovery period, except for the two high-dose female rats and two high-dose male monkeys, which were considered related to the increased RBCs, chronic blood hyperviscosity and chronic cardiac injury. EPO-018B is supposed to be subcutaneously injected once every month and the intended human therapeutic dose is 0.025 mg/kg. The study findings at 0.2 mg/kg for rats and 0.3 mg/kg for monkeys were considered to be the study NOAEL (the no observed adverse effect level), which were more than ten times the intended human therapeutic dose. Higher doses caused adverse effects related to the liver toxicity, cardiotoxicity, appearance of neutralizing antibodies of EPO-018B and the decrease of serum glucose and cholesterol. Most treatment-induced effects were reversible or revealed ongoing recovery upon the discontinuation of treatment. The sequelae occurred in rats and monkeys were considered secondary to exaggerated pharmacology and would less likely occur in the intended patient population. As to the differences between human beings and animals, the safety of EPO-018B need to be further confirmed in the future clinical studies. - Highlights: • EPO-018B is a newly developed synthetic peptide-based ESA. • The evaluation contained studies of 6 months in rats and 9 months in monkeys. • The safety studies provided further evidences in future clinical trials. • Most toxic effects were reversible and need more evidences in clinical studies.« less

Development of an embryo toxicity test with the pond snail Lymnaea stagnalis using the model substance tributyltin and common solvents.

PubMed

Bandow, Cornelia; Weltje, Lennart

2012-10-01

The development of a chronic mollusc toxicity test is a current work item on the agenda of the OECD. The freshwater pond snail Lymnaea stagnalis is one of the candidate snail species for such a test. This paper presents a 21-day chronic toxicity test with L. stagnalis, focussing on embryonic development. Eggs were collected from freshly laid egg masses and exposed individually until hatching. The endpoints were hatching success and mean hatching time. Tributyltin (TBT), added as TBT-chloride, was chosen as model substance. The selected exposure concentrations ranged from 0.03 to 10 μg TBT/L (all as nominal values) and induced the full range of responses. The embryos were sensitive to TBT (the NOEC for mean hatching time was 0.03 μg TBT/L and the NOEC for hatching success was 0.1 μg TBT/L). In addition, data on maximum limit concentrations of seven common solvents, recommended in OECD aquatic toxicity testing guidelines, are presented. Among the results, further findings as average embryonic growth and mean hatching time of control groups are provided. In conclusion, the test presented here could easily be standardised and is considered useful as a potential trigger to judge if further studies, e.g. a (partial) life-cycle study with molluscs, should be conducted. Copyright © 2012 Elsevier B.V. All rights reserved.

Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

PubMed Central

2011-01-01

The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. PMID:21410251

The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine

PubMed Central

Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H.; Montgomery, Therese

2015-01-01

Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity. PMID:21194370

Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock. A review.

PubMed

López, T A; Cid, M S; Bianchini, M L

1999-06-01

The literature on Conium maculatum biochemistry and toxicology, dispersed in a large number of scientific publications, has been put together in this review. C. maculatum is a weed known almost worldwide by its toxicity to many domestic animals and to human beings. It is an Umbelliferae, characterized by long, hollow stems, reaching up to 2 m height at maturity, producing a large amount of lush foliage during its vegetative growth. Its flowers are white, grouped in umbels formed by numerous umbellules. It produces a large number of seeds that allow the plant to form thick stands in modified soils, sometimes encroaching on cultivated fields, to the extent of impeding the growth of any other vegetation inside the C. maculatum area of growth. Eight piperidinic alkaloids have been identified in this species. Two of them, gamma-coniceine and coniine are generally the most abundant and they account for most of the plant acute and chronic toxicity. These alkaloids are synthesized by the plant from eight acetate units from the metabolic pool, forming a polyketoacid which cyclises through an aminotransferase and forms gamma-coniceine as the parent alkaloid via reduction by a NADPH-dependent reductase. The acute toxicity is observed when animals ingest C. maculatum vegetative and flowering plants and seeds. In a short time the alkaloids produce a neuromuscular blockage conducive to death when the respiratory muscles are affected. The chronic toxicity affects only pregnant animals. When they are poisoned by C. maculatum during the fetuses organ formation period, the offspring is born with malformations, mainly palatoschisis and multiple congenital contractures (MCC; frequently described as arthrogryposis). Acute toxicity, if not lethal, may resolve in the spontaneous recovery of the affected animals provided further exposure to C. maculatum is avoided. It has been observed that poisoned animals tend to return to feed on this plant. Chronic toxicity is irreversible and although MCC can be surgically corrected in some cases, most of the malformed animals are lost. Since no specific antidote is available, prevention is the only way to deal with the production loses caused by this weed. Control with herbicides and grazing with less susceptible animals (such as sheep) have been suggested. C. maculatum alkaloids can be transferred to milk and to fowl muscle tissue through which the former can reach the human food chain. The losses produced by C. maculatum chronic toxicity may be largely underestimated, at least in some regions, because of the difficulty in associate malformations in offspring with the much earlier maternal poisoning.

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the special conditions for C1, C2, C3, C4, C5.... Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C2: 1...

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).

PubMed

Tallarico, Michael; Foster, Jared C; Seisler, Drew; Lafky, Jacqueline M; Hurria, Arti; Jatoi, Aminah; Cohen, Harvey J; Muss, Hyman B; Bartlett, Nancy; Cheson, Bruce D; Jung, Sin-Ho; Leonard, John P; Byrd, John C; Nabhan, Chadi

2018-07-01

Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of the aphrodisiac activity of Tribulus terrestris Linn. in sexually sluggish male albino rats

PubMed Central

Singh, Surender; Nair, Vinod; Gupta, Yogendra K.

2012-01-01

Objectives: To study the effect of acute and repeated dose administration of lyophilized aqueous extract of the dried fruits of Tribulus terrestris (LAET) on sexual function in sexually sluggish male albino rats. Materials and Methods: Aphrodisiac activity of the test drug was evaluated in terms of exhibited sexual behavior. In order to assess the effect of chronic T. terrestris exposure on the hypothalamus--pituitary--gonadal axis, testosterone level estimation and sperm count were carried out. Twenty-eight-day oral toxicity studies were carried out to evaluate the long-term effects of the LAET administration on different body systems. Results: A dose-dependent improvement in sexual behavior was observed with the LAET treatment as characterized by an increase in mount frequency, intromission frequency, and penile erection index, as well as a decrease in mount latency, intromission latency, and ejaculatory latency. The enhancement of sexual behavior was more prominent on chronic administration of LAET. Chronic administration of LAET produced a significant increase in serum testosterone levels with no significant effect on the sperm count. No overt body system dysfunctions were observed in 28-day oral toxicity study. Conclusions: Findings of the present study validate the traditional use of T. terrestris as a sexual enhancer in the management of sexual dysfunction in males. PMID:22368416

Effect of nephrotoxic treatment with gentamicin on rats chronically exposed to uranium.

PubMed

Rouas, Caroline; Stefani, Johanna; Grison, Stéphane; Grandcolas, Line; Baudelin, Cédric; Dublineau, Isabelle; Pallardy, Marc; Gueguen, Yann

2011-01-11

Uranium is a radioactive heavy metal with a predominantly chemical toxicity, affecting especially the kidneys and more particularly the proximal tubular structure. Until now, few experimental studies have examined the effect of chronic low-dose exposure to uranium on kidney integrity: these mainly analyse standard markers such as creatinine and urea, and none has studied the effect of additional co-exposure to a nephrotoxic agent on rats chronically exposed to uranium. The aim of the present study is to examine the potential cumulative effect of treating uranium-exposed rats with a nephrotoxic drug. Neither physiological indicators (diuresis and creatinine clearance) nor standard plasma and urine markers (creatinine, urea and total protein) levels were deteriorated when uranium exposure was combined with gentamicin-induced nephrotoxicity. A histological study confirmed the preferential impact of gentamicin on the tubular structure and showed that uranium did not aggravate the histopathological renal lesions. Finally, the use of novel markers of kidney toxicity, such as KIM-1, osteopontin and kallikrein, provides new knowledge about the nephrotoxicity threshold of gentamicin, and allows us to conclude that under our experimental conditions, low dose uranium exposure did not induce signs of nephrotoxicity or enhance renal sensitivity to another nephrotoxicant. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Toxicity, mechanism and health effects of some heavy metals

PubMed Central

Jaishankar, Monisha; Tseten, Tenzin; Anbalagan, Naresh; Beeregowda, Krishnamurthy N.

2014-01-01

Heavy metal toxicity has proven to be a major threat and there are several health risks associated with it. The toxic effects of these metals, even though they do not have any biological role, remain present in some or the other form harmful for the human body and its proper functioning. They sometimes act as a pseudo element of the body while at certain times they may even interfere with metabolic processes. Few metals, such as aluminium, can be removed through elimination activities, while some metals get accumulated in the body and food chain, exhibiting a chronic nature. Various public health measures have been undertaken to control, prevent and treat metal toxicity occurring at various levels, such as occupational exposure, accidents and environmental factors. Metal toxicity depends upon the absorbed dose, the route of exposure and duration of exposure, i.e. acute or chronic. This can lead to various disorders and can also result in excessive damage due to oxidative stress induced by free radical formation. This review gives details about some heavy metals and their toxicity mechanisms, along with their health effects. PMID:26109881

Evaluation of influence of sediment on the sensitivity of a unionid mussel (Lampsilis siliquoidea) to ammonia in 28-day water exposures

USGS Publications Warehouse

Wang, N.; Consbrock, R.A.; Ingersoll, C.G.; Barnhart, M.C.

2011-01-01

A draft update of the U.S. Environmental Protection Agency ambient water quality criteria (AWQC) for ammonia substantially lowers the ammonia AWQC, primarily due to the inclusion of toxicity data for freshwater mussels. However, most of the mussel data used in the updated AWQC were generated from water-only exposures and limited information is available on the potential influence of the presence of a substrate on the response of mussels in laboratory toxicity tests. Our recent study demonstrated that the acute sensitivity of mussels to ammonia was not influenced by the presence of substrate in 4-d laboratory toxicity tests. The objective of the current study was to determine the sensitivity of mussels to ammonia in chronic 28-d water exposures with the sediment present (sediment treatment) or absent (water-only treatment). The chronic toxicity test was conducted starting with two-month-old juvenile mussels (fatmucket, Lampsilis siliquoidea) in a flow-through diluter system, which maintained consistent pH (???8.3) and six concentrations of total ammonia nitrogen (N) in overlying water and in sediment pore water. The chronic value (ChV, geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) was 0.36mgN/L for survival or biomass in the water-only treatment, and was 0.66mgN/L for survival and 0.20mgN/L for biomass in the sediment treatment. The 20% effect concentration (EC20) for survival was 0.63mgN/L in the water-only treatment and was 0.86mgN/L in the sediment treatment (with overlapping 95% confidence intervals; no EC20 for biomass was estimated because the data did not meet the conditions for any logistic regression analysis). The similar ChVs or EC20s between the water-only treatment and the sediment treatment indicate that the presence of sediment did not substantially influence the sensitivity of juvenile mussels to ammonia in the 28-d chronic laboratory water exposures. ?? 2011 SETAC.

Evaluation of influence of sediment on the sensitivity of a unionid mussel (Lamsilis silquoidea) to ammonia in 28-day water exposures

USGS Publications Warehouse

Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Barnhart, M. Christopher

2011-01-01

A draft update of the U.S. Environmental Protection Agency ambient water quality criteria (AWQC) for ammonia substantially lowers the ammonia AWQC, primarily due to the inclusion of toxicity data for freshwater mussels. However, most of the mussel data used in the updated AWQC were generated from water-only exposures and limited information is available on the potential influence of the presence of a substrate on the response of mussels in laboratory toxicity tests. Our recent study demonstrated that the acute sensitivity of mussels to ammonia was not influenced by the presence of substrate in 4-d laboratory toxicity tests. The objective of the current study was to determine the sensitivity of mussels to ammonia in chronic 28-d water exposures with the sediment present (sediment treatment) or absent (water-only treatment). The chronic toxicity test was conducted starting with two-month-old juvenile mussels (fatmucket, Lampsilis siliquoidea) in a flow-through diluter system, which maintained consistent pH (≈8.3) and six concentrations of total ammonia nitrogen (N) in overlying water and in sediment pore water. The chronic value (ChV, geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) was 0.36 mg N/L for survival or biomass in the water-only treatment, and was 0.66 mg N/L for survival and 0.20 mg N/L for biomass in the sediment treatment. The 20% effect concentration (EC20) for survival was 0.63 mg N/L in the water-only treatment and was 0.86 mg N/L in the sediment treatment (with overlapping 95% confidence intervals; no EC20 for biomass was estimated because the data did not meet the conditions for any logistic regression analysis). The similar ChVs or EC20s between the water-only treatment and the sediment treatment indicate that the presence of sediment did not substantially influence the sensitivity of juvenile mussels to ammonia in the 28-d chronic laboratory water exposures.

Acute and sub-chronic oral toxicity assessment of the aqueous extract leaves of Ficus glumosa Del. (Moraceae) in rodents.

PubMed

Ntchapda, Fidèle; Abakar, Djedouboum; Kom, Blaise; Nana, Paulin; Hamadjida, Adjia; Dimo, Théophile

2014-01-01

Ficus glumosa Del (Moraceae), a plant used in traditional medicine in Cameroon, Senegal, and East Africa for the treatment of edema, hemorrhoid, cardiovascular diseases especially hypertension. The present study evaluated the potential toxicity of the aqueous extract of the leaves of F.glumosa in acute and sub-chronic administration in rodents. Acute toxicity was evaluated on 3 months old mice of both sexes and weighing 20-30 g. A single dose (2-12 g/kg) of F. glumosa was administered orally to mice. Animal behavior, adverse effects, and mortality were determined for 14 days. In sub-chronic toxicity studied in both sexes of 9 weeks old rats and weighing 100-120 g at the start of the experiment, animals were treated orally with a daily dose of 300, 600 and 1200 mg/kg of the aqueous extract of the leaves of F. glumosa for 6 weeks. The body weight change, food, and water consumption, were determined throughout the experimental period, while the relative organ weights, the hematological and biochemical parameters of blood and urine, as well as the histology of tissues kidney and liver, were recorded at the end of the experiment. For acute treatment, no dose used induced critical behavioral changes or death. In sub-chronic treatment, daily oral administration of F. glumosa at the dose of 300, 600, and 1200 mg/kg resulted in a significant increase in body weight relative to food and water consumption in the last week of treatment. The relative organ weights were not affected by treatment. No hematological changes were observed except the significant increase in platelets. Aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total protein, increased while the total cholesterol, triacylglycerol, conjugated bilirubin, and total bilirubin significantly decreased. Index of renal function showed a decrease of creatinine, urea, uric acid and Na(+), Cl(-) and Ca(2+), and inorganic phosphate. The histology of liver and kidney showed no significant alteration of tissue. These observations support the traditional use of F. glumosa in the treatment of hypertension. These results have shown that F. glumosa has a safety margin for therapeutic use.

Estimation of vanadium water quality benchmarks for the protection of aquatic life with relevance to the Athabasca Oil Sands region using species sensitivity distributions.

PubMed

Schiffer, Stephanie; Liber, Karsten

2017-11-01

Elevated vanadium (V) concentrations in oil sands coke, which is produced and stored on site of some major Athabasca Oil Sands companies, could pose a risk to aquatic ecosystems in northern Alberta, Canada, depending on its future storage and utilization. In the present study, V toxicity was determined in reconstituted Athabasca River water to various freshwater organisms, including 2 midge species (Chironomus dilutus and Chironomus riparius; 4-d and 30-d to 40-d exposures) and 2 freshwater fish species (Oncorhynchus mykiss and Pimephales promelas; 4-d and 28-d exposures) to facilitate estimation of water quality benchmarks. The acute toxicity of V was 52.0 and 63.2 mg/L for C. dilutus and C. riparius, respectively, and 4.0 and 14.8 mg V/L for P. promelas and O. mykiss, respectively. Vanadium exposure significantly impaired adult emergence of C. dilutus and C. riparius at concentrations ≥16.7 (31.6% reduction) and 8.3 (18.0% reduction) mg/L, respectively. Chronic toxicity in fish presented as lethality, with chronic 28-d LC50s of 0.5 and 4.3 mg/L for P. promelas and O. mykiss, respectively. These data were combined with data from the peer-reviewed literature, and separate acute and chronic species sensitivity distributions (SSDs) were constructed. The acute and chronic hazardous concentrations endangering only 5% of species (HC5) were estimated as 0.64 and 0.05 mg V/L, respectively. These new data for V toxicity to aquatic organisms ensure that there are now adequate data available for regulatory agencies to develop appropriate water quality guidelines for use in the Athabasca Oil Sands region and elsewhere. Until then, the HC5 values presented in the present study could serve as interim benchmarks for the protection of aquatic life from exposure to hazardous levels of V in local aquatic environments. Environ Toxicol Chem 2017;36:3034-3044. © 2017 SETAC. © 2017 SETAC.

Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

PubMed Central

Rosales, Ivy

2018-01-01

Background Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p = 0.09), 34.1 mL/min at 6 months (p = 0.63), 34.9 mL/min at 12 months (p = 0.57), and 39.6 mL/min at 24 months after conversion (p = 0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months. PMID:29854421

Oxidative toxic stress in workers occupationally exposed to ceramic dust: A study in a ceramic manufacturing industry.

PubMed

Shad, Mehri Keshvari; Barkhordari, Abolfaz; Mehrparvar, Amir Houshang; Dehghani, Ali; Ranjbar, Akram; Moghadam, Rashid Heidari

2016-09-27

Exposure to compounds used in ceramic industries appears to be associated with induction of oxidative toxic stress. This cross sectional study was undertaken to assess the oxidative toxic stress parameters associated with occupational exposure to ceramic dust. Forty ceramic-exposed workers from a ceramic manufacturing industry and 40 unexposed referent subjects were studied. A questionnaire containing information regarding demographic variables, occupational history, history of any chronic disease, antioxidant consumption, and use of therapeutic drugs was administrated to them. Oxidative toxic stress biomarkers including lipid peroxidation (LPO), total antioxidant power (TAP), levels of total Thiol groups (TTG) and catalase (CAT) activity were measured. Significant increments in blood LPO levels, CAT activity and concomitant lower TAP were observed in ceramic exposed workers in comparison to referent group. No statistically significant difference was noted between the means of TTG levels between the groups. Findings of the study indicate that occupational exposure to ceramic dust induces oxidative toxic stress. Supplementation of workers with antioxidants may have beneficial effects on oxidative damages in ceramic industries.

Occurrence and risk assessment of an azo dye - The case of Disperse Red 1.

PubMed

Vacchi, Francine Inforçato; Von der Ohe, Peter Carsten; Albuquerque, Anjaína Fernandes de; Vendemiatti, Josiane Aparecida de Souza; Azevedo, Carina Cristina Jesus; Honório, Jaqueline Gonçalves; Silva, Bianca Ferreira da; Zanoni, Maria Valnice Boldrin; Henry, Theodore B; Nogueira, Antonio J; Umbuzeiro, Gisela de Aragão

2016-08-01

Water quality criteria to protect aquatic life are not available for most disperse dyes which are often used as commercial mixtures in textile coloration. In this study, the acute and chronic toxicity of the commercial dye Disperse Red 1 (DR1) to eight aquatic organisms from four trophic levels was evaluated. A safety threshold, i.e. Predicted No-Effect Concentration (PNEC), was derived based on the toxicity information of the commercial product and the purified dye. This approach was possible because the toxicity of DR1 was accounting for most of the toxicity of the commercial mixture. A long-term PNEC of 60 ng L(-1) was proposed, based on the most sensitive chronic endpoint for Daphnia similis. A short-term PNEC of 1800 ng L(-1) was proposed based on the most sensitive acute endpoint also for Daphnia similis. Both key studies have been evaluated with the new "Criteria for Reporting and Evaluating ecotoxicity Data" (CRED) methodology, applying more objective criteria to assess the quality of toxicity tests, resulting in two reliable and relevant endpoints with only minor restrictions. HPLC-MS/MS was used to quantify the occurrence of DR1 in river waters of three sites, influenced by textile industry discharges, resulting in a concentration range of 50-500 ng L(-1). The risk quotients for DR1 obtained in this work suggest that this dye can pose a potential risk to freshwater biota. To reduce uncertainty of the derived PNEC, a fish partial or full lifecycle study should be performed. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-07-01

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

In vivo nanotoxicological profile of graphene oxide

NASA Astrophysics Data System (ADS)

Durán, Marcela; Durán, Nelson; Fávaro, Wagner J.

2017-06-01

Graphene oxide, a widely studied nano materials, exhibits numerous beneficial effects in medical devices. The graphene sample Graphene oxide (GO):Single-layer graphene oxide, purity 99%, thickness 0.7-1.2 nm (AFM); ~300-800nm X&Y dimensions is the standard size <450 nm & 1-20 µm lateral dimensions from Cheap Tubes Inc., Bratleboro, USA was selected for this study. Characterization of GO and stability were previously studied. All the assays were carried out at a concentration of 1 mg/mL (stock suspension by ultrasonication)(stable 10 days). In this study the first parameter evaluated was in animal toxicity in acute and chronic responses. The second one was to observe the morphology and histological changes on major organs, like signs of inflammatory areas. A total of 25 rats (Fischer 344) were divide in 5 groups (n = 5 animals): negative control group (NCT); Positive cancer control group (PCCT); GO group-1 (GO 1); GO group-2 (GO 2) and GO group-3 (GO 3), with different concentrations of graphene oxide. All the groups were treated by via intra peritoneal (i.p) administration. Biochemical and histopathology results of acute toxicity showed no alterations. In the chronic toxicity was found deposit sections and morphology alterations in different tissues (inflammations). Genotoxicity was dose dependent of GO. This study gave us the limit concentrations of GO free for any biological study.

The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML Study Group

PubMed Central

Iriyama, Noriyoshi; Ohashi, Kazuteru; Hashino, Satoshi; Kimura, Shinya; Nakaseko, Chiaki; Takano, Hina; Hino, Masayuki; Uchiyama, Michihiro; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

2017-01-01

Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment. PMID:29033428

The Toxicity Estimation Software Tool (T.E.S.T.)

EPA Science Inventory

The Toxicity Estimation Software Tool (T.E.S.T.) has been developed to estimate toxicological values for aquatic and mammalian species considering acute and chronic endpoints for screening purposes within TSCA and REACH programs.

Propylene glycol monomethyl ether (PGME): inhalation toxicity and carcinogenicity in Fischer 344 rats and B6C3F1 mice.

PubMed

Spencer, Pamela J; Crissman, James W; Stott, William T; Corley, Richard A; Cieszlak, Frank S; Schumann, Alan M; Hardisty, Jerry F

2002-01-01

A series of inhalation studies with propylene glycol monomethyl ether (PGME) vapor were undertaken to characterize its subchronic toxicity in mice and chronic toxicity/oncogenicity in rats and mice. Groups of male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1,000, or 3,000 ppm vapor from 1 week to 2 years. Primary treatment-related effects included: initial sedation of animals exposed to 3,000 ppm and its subsequent resolution correlating with induction of hepatic mixed function oxidase activity and S-phase DNA synthesis; elevated mortality in high-exposure male rats and mice (chronic study); elevated deposition of alpha2u-globulin (alpha2U-G) and associated nephropathy and S-phase DNA synthesis in male rat kidneys; accelerated atrophy of the adrenal gland X-zone in female mice (subchronic study only); and increased occurrence and/or severity of eosinophilic foci of altered hepatocytes in male rats. No toxicologically relevant statistically significant increases in neoplasia occurred in either species. A numerical increase in the incidence of kidney adenomas occurred in intermediate-exposure male rats; however, the association with alpha2U-G nephropathy, a male rat specific effect, indicated a lack of relevance for human risk assessment.

Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

PubMed

Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

2017-06-01

In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

Assessment of in vivo systemic toxicity and biodistribution of iron-doped silica nanoshells.

PubMed

Mendez, Natalie; Liberman, Alexander; Corbeil, Jacqueline; Barback, Christopher; Viveros, Robert; Wang, James; Wang-Rodriguez, Jessica; Blair, Sarah L; Mattrey, Robert; Vera, David; Trogler, William; Kummel, Andrew C

2017-04-01

Silica nanoparticles are an emerging class of biomaterials which may be used as diagnostic and therapeutic tools for biomedical applications. In particular, hollow silica nanoshells are attractive due to their hollow core. Approximately 70% of a 500 nm nanoshell is hollow, therefore more particles can be administered on a mg/kg basis compared to solid nanoparticles. Additionally, their nanoporous shell permits influx/efflux of gases and small molecules. Since the size, shape, and composition of a nanoparticle can dramatically alter its toxicity and biodistribution, the toxicology of these nanomaterials was assessed. A single dose toxicity study was performed in vivo to assess the toxicity of 500 nm iron-doped silica nanoshells at clinically relevant doses of 10-20 mg/kg. This study showed that only a trace amount of silica was detected in the body 10 weeks post-administration. The hematology, biochemistry and pathological results show that the nanoshells exhibit no acute or chronic toxicity in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions.

PubMed

Bain, Barbara J; Ahmad, Shahzaib

2015-11-01

Many cases reported as 'chronic neutrophilic leukaemia' have had an associated plasma cell neoplasm. Recent evidence suggests that the great majority of such cases represent a neutrophilic leukaemoid reaction to the underlying multiple myeloma or monoclonal gammopathy of undetermined significance. We have analysed all accessible reported cases to clarify the likely diagnosis and to ascertain whether toxic granulation, Döhle bodies and an increased neutrophil alkaline phosphatase score were useful in making a distinction between chronic neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established that all these changes occur in both conditions. Toxic granulation and Döhle bodies are more consistently present in leukaemoid reactions but also occur quite frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase score is increased in both conditions and is of no value in making a distinction. © 2015 John Wiley & Sons Ltd.

Determination of the Chronic Mammalian Toxicological Effects of RDX: (Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5- Trinitro-1,3,5-Triazine (RDX) in the Fischer 344 Rat). Volume 1.

DTIC Science & Technology

1983-11-01

content. C . An J ma Is *a Fischer 344 (F344) rats, obtained from Harlan Sprague-Dawley, Madison , WI, were used for this study. Four hundred and thirty...Seminal vesicles "Skin, abdominal Spinal cord (cervical, thoracic, lumbar ) *Spleen Sternum, Including bone marrow Stomach *Testes Thymus Thyroids...abdominal * Spinal cord (cervical, thoracic and lumbar ) Spleen Sternum Including bone marrow Stomach Tissue masses Thyroids (parathyroids) Trachea

The toxicity of aluminium in humans.

PubMed

Exley, C

2016-06-01

We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to aluminum and aluminum fluoride.

PubMed

Sharma, Shweta; Sharma, K P; Sharma, Subhasini

2016-12-01

Aluminum is ingested through foods, water, air, and even drugs. Its intake is potentiated further through foods and tea prepared in aluminum utensils and Al salt added in the drinking water for removal of suspended impurities and also fluoride in the affected areas. The ameliorating role of a blue green alga Spirulina is well documented to various pollutants in the animal models. We, therefore, examined its protective role (230 mg/kg body weight) on the hematology of male Swiss albino mice treated with aluminum (sub-acute = 78.4 mg/kg body weight for 7 days, sub-chronic = 7.8 mg/kg body weight for 90 days) and aluminum fluoride (sub-acute = 103 mg/kg body weight, sub-chronic = 21 mg/kg body weight), along with their recovery after 90 days of sub-chronic exposure. This study revealed significant reduction in the values of RBC (5-18 %), Hb (15-17 %), PCV (8-14 %), and platelets (26-36 %), and increase in WBC (54-124 %) in the treated mice, particularly after sub-acute exposure. Aluminum fluoride was comparatively more toxic than aluminum. Further, Spirulina supplement not only alleviated toxicity of test chemicals in Swiss albino mice but also led to their better recovery after withdrawal.

60-Day chronic exposure to low concentrations of HgCl2 impairs sperm quality: hormonal imbalance and oxidative stress as potential routes for reproductive dysfunction in rats.

PubMed

Martinez, Caroline S; Torres, João Guilherme D; Peçanha, Franck M; Anselmo-Franci, Janete A; Vassallo, Dalton V; Salaices, Mercedes; Alonso, María J; Wiggers, Giulia A

2014-01-01

Mercury is a toxic and bio-accumulative heavy metal of global concern. While good deals of research have been conducted on the toxic effects of mercury, little is known about the mechanisms involved in the pathogenesis of male reproductive dysfunction induced by mercury. Therefore, the purpose of this study was to assess the effects and underlying mechanisms of chronic mercury exposure at low levels on male reproductive system of rats. Three-month-old male Wistar rats were divided into two groups and treated for 60 days with saline (i.m., Control) and HgCl2 (i.m. 1st dose: 4.6 µg/kg, subsequent doses 0.07 µg/kg/day). We analyzed sperm parameters, hormonal levels and biomarkers of oxidative stress in testis, epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm production, count and motility and increased head and tail morphologic abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels, increased lipid peroxidation on testis and decreased antioxidant enzymes activities (superoxide dismutase and catalase) on reproductive organs. Our data demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs sperm quality and promotes hormonal imbalance. The raised oxidative stress seems to be a potential mechanism involved on male reproductive toxicity by mercury.

Haloactamides versus halomethanes formation and toxicity in chloraminated drinking water.

PubMed

Yang, Fan; Zhang, Jing; Chu, Wenhai; Yin, Daqiang; Templeton, Michael R

2014-06-15

In this study we quantified the concentrations of nine haloacetamides (HAcAms) and nine halomethanes (HMs) in the final waters of five drinking water treatment plants (DWTPs) that use either chlorination or chloramination for disinfection and evaluated the toxicity of dichloroacetamide (DCAcAm) and dichloromethane (DCM) in normal rat kidney (NRK) cells using four in vitro toxicity assays. All the DWTPs final waters contained primarily di-HAcAms, followed by tri- and mono-HAcAms, and DCAcAm was the most abundant species of the 9 HAcAms, regardless of chlorination or chloramination being applied. In the final waters of DWTPs using chlorination, tri-HMs (trihalomethanes, THMs) accounted for the majority of HMs, whereas chloramination resulted in more di-HMs (especially DCM) than THMs. All four in vitro toxicity assays indicated that the NRK cell chronic cytotoxicity and acute genotoxicity of DCAcAm were substantially higher than that of DCM. In view of observed occurrence concentrations and quantified toxicity levels, the findings of this study suggest that DCAcAm represents a higher toxicity risk than DCM in chloraminated drinking waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

PubMed

Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

2014-08-01

Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of oxidative stress in organophosphate and nerve agent toxicity

PubMed Central

Pearson, Jennifer N.; Patel, Manisha

2016-01-01

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

Chronic sensitivity of white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) to cadmium, copper, lead, or zinc in laboratory water-only exposures

USGS Publications Warehouse

Wang, Ning; Ingersoll, Christopher G.; Dorman, Rebecca A.; Brumbaugh, William G.; Mebane, Christopher A.; Kunz, James L.; Hardesty, Douglas K.

2014-01-01

Chronic toxicity of cadmium, copper, lead, or zinc to white sturgeon (Acipenser transmontanus) and rainbow trout (Oncorhynchus mykiss) was evaluated in water-only exposures started with newly hatched larvae or approximately 1-mo-old juveniles. The 20% effect concentration (EC20) for cadmium from the sturgeon tests was higher than the EC20 from the trout tests, whereas the EC20 for copper, lead, or zinc for the sturgeon were lower than those EC20s for the trout. When the EC20s from the present study were included in compiled toxicity databases for all freshwater species, species mean chronic value for white sturgeon was in a relatively low percentile of the species sensitivity distribution for copper (9th percentile) and in the middle percentile for cadmium (55th percentile), zinc (40th percentile), or lead (50th percentile). However, the species mean chronic value for rainbow trout was in a high percentile for copper, lead, and zinc (∼68th–82nd percentile), but in a low percentile for cadmium (23rd percentile). The trout EC20s for each of the 4 metals and the sturgeon EC20s for cadmium or lead were above US Environmental Protection Agency chronic ambient water quality criteria (AWQC) or Washington State chronic water quality standards (WQS), whereas the sturgeon EC20s for copper or zinc were approximately equal to or below the chronic AWQC and WQS. In addition, acute 50% effect concentrations (EC50s) for copper obtained in the first 4 d of the chronic sturgeon test were below the final acute value used to derive acute AWQC and below acute WQS for copper.

Acute and chronic toxicity assessment of benzylpenicillin G residue in heat-treated animal food products.

PubMed

Cui, Cheng; Zhang, Xiang; Wang, Yang; Lu, Shiying; Lu, Huijun; Hui, Qi; Ahmad, Waqas; Cai, Yan; Liu, Xilin; Liu, Lingjiu; Shi, Fengfeng; Liu, Yanyan; Zhao, Ke; Zhai, FeiFei; Xiang, Yangzhen; Hu, Pan; Li, Yansong; Ren, Honglin; Jin, Ningyi; Liu, Zengshan

2018-07-01

The current level of penicillin use and its persisting residue in livestock is potentially concerning; the toxicity of penicillin residue in heat-treated animal food products (HAFP) is yet to be elucidated. In this study, the acute and chronic toxicity of benzylpenicillin G (BPG) residue in HAFP was investigated in a mouse model. The calculated LD 50 of BPG heated to cooking temperature (BPHCT) was 933.04 mg kg -1 [b.w.] intraperitoneally corresponding to 3.75 times lower than its prototype. Mice fed on the experimental diet containing heat-treated beef with high BPG levels for 6 months displayed a reduction in body weight and altered serum values indicating for liver and renal function. Further, the organ ratios of intestinal and spleen were increased. Histopathological changes were observed in the liver, lung and parenchyma testis tissue. BPHCT residue induced sperm aberration and micronucleated polychromatic erythrocytes formation. Present results indicate that prolonged exposure of BPHCT at higher residue levels might have an impact on public health. Importantly the toxic concentrations of BPHCT are relatively high compared with levels that would result from the degradation of antibiotic residues in meat from animals that have received a therapeutic dose of BPG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Internal versus External Dose for Describing Ternary Metal Mixture (Ni, Cu, Cd) Chronic Toxicity to Lemna minor.

PubMed

Gopalapillai, Yamini; Hale, Beverley A

2017-05-02

Simultaneous determinations of internal dose ([M] tiss ) and external doses ([M] tot , {M 2+ } in solution) were conducted to study ternary mixture (Ni, Cu, Cd) chronic toxicity to Lemna minor in alkaline solution (pH 8.3). Also, concentration addition (CA) based on internal dose was evaluated as a tool for risk assessment of metal mixture. Multiple regression analysis of dose versus root growth inhibition, as well as saturation binding kinetics, provided insight into interactions. Multiple regressions were simpler for [M] tiss than [M] tot and {M 2+ }, and along with saturation kinetics to the internal biotic ligand(s) in the cytoplasm, they indicated that Ni-Cu-Cd competed for uptake into plant, but once inside, only Cu-Cd shared a binding site. Copper inorganic complexes (hydroxides, carbonates) played a role in metal bioavailability in single metal exposure but not in mixtures. Regardless of interactions, the current regulatory approach of using CA based on [M] tot can sufficiently predict mixture toxicity (∑TU close to 1), but CA based on [M] tiss was closest to unity across a range of doses. Internal dose integrates all metal-metal interactions in solution and during uptake into the organism, thereby providing a more direct metric describing toxicity.

Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: arsenic, manganese, fluoride, iron, and uranium.

PubMed

Bacquart, Thomas; Frisbie, Seth; Mitchell, Erika; Grigg, Laurie; Cole, Christopher; Small, Colleen; Sarkar, Bibudhendra

2015-06-01

In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic substances. Copyright © 2015 Elsevier B.V. All rights reserved.

Light-stick: A problem of marine pollution in Brazil.

PubMed

Cesar-Ribeiro, Caio; Rosa, Helena Costi; Rocha, Daniele Oliveira; Dos Reis, Camila Galli Baldini; Prado, Tabata Sarti; Muniz, Daniela Hernandes Coimbra; Carrasco, Raquel; Silva, Flávia Milão; Martinelli-Filho, José Eduardo; Palanch-Hans, Maria Fernanda

2017-04-15

Light-sticks are used as bait in surface long-line fishing, to capture swordfish and other large pelagic predators. When discharged in the ocean, it may reach the beaches. The traditional Brazilian community of Costa dos Coqueiros, Bahia, use light-sticks as a medicine for rheumatism, vitiligo and mycoses. It may affect the marine life when its content leak in the open ocean. This work evaluated and identified the acute and chronic toxicity of the light-stick. A high acute toxicity was observed in the mobility/mortality of Artemia sp.; in the fertilization of sea urchin eggs, and a high chronic toxicity in the development of the pluteus larvae of the same sea urchin. The main compounds that probably caused toxicity were the volatiles such as the fluorescent PAH and oxidants such as the hydrogen peroxide. Its disposal in the open ocean is a potential threat for marine life. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Fresh Look at Road Salt: Aquatic Toxicity and Water-Quality Impacts on Local, Regional, and National Scales

PubMed Central

2010-01-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30 800 μS/cm (Cl = 11 200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria. PMID:20806974

A fresh look at road salt: Aquatic toxicity and water-quality impacts on local, regional, and national scales

USGS Publications Warehouse

Corsi, S.R.; Graczyk, D.J.; Geis, S.W.; Booth, N.L.; Richards, K.D.

2010-01-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30 800 ??S/cm (Cl = 11 200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria. ?? 2010 American Chemical Society.

Chronic exposure of μg/L range Bisphenol A to adult zebrafish (Danio rerio) leading to adipogenesis

NASA Astrophysics Data System (ADS)

Ngo, Mai Thi; Doan, Thao Thi-Phuong; Nguyen, Cong Thanh; Vo, Diem Thi-Ngoc; Do, Chi Hong-Lan; Le, Nga Phi

2017-09-01

Bisphenol A (BPA) is known as an endocrine disruptor compound and commonly found in food-packaging plastics and in aquatic environment. It is scientifically concerned that BPA may causes significant health risks to human and aquatic animals. In fact, most of scientific studies have been conducted with BPA-acute toxicity in early stages of animal development, while far lesser researches have been focused on BPA-chronic toxicity in adults. This study was to investigate the chronic effects of environmental 1, 10 and 100 µg/L BPA to four-week-old zebrafishes (Danio rerio) after 60 days of exposure in terms of changing of body morphology, hepatocyte morphology and the transcriptional expression of biomarker gene for lipid metabolism. As a result, significant effects were found in: 1/ the increase of body weight, but not body length; 2/ the increase in the number of vacuolated hepatocytes corresponding to relatively higher glycogen and lipid content; 3/ shifting hepatocyte morphology to basophilic cytoplasm and cytoplasmic and/or nuclear enlargement, but not inflammation signs (macrophages, granuloma, fibrosis/cirrhosis); 4/ the decrease of mRNA level of PPARγ and C/EBPα genes in liver. Our study here indicates that the exposure to μg/L range concentration of BPA leads to adipogensis in adult zebrafishes.

Negative pressure and nanocrystalline silver dressings for nonhealing ulcer: A randomized pilot study.

PubMed

Sáez-Martín, Luis C; García-Martínez, Lourdes; Román-Curto, Concepción; Sánchez-Hernández, Miguel V; Suárez-Fernández, Ricardo M

2015-01-01

Chronic wounds have a high prevalence and wound care, treatment, and prevention consume large quantities of resources. Chronic wounds are a growing challenge for clinicians. A prospective randomized pilot study was conducted to assess the effectiveness in terms of reduction in area and safety of the combined use of negative-pressure wound therapy and nanocrystalline silver dressings as compared to negative pressure wound therapy (NPWT) alone in the management of outpatients with chronic wounds. A total of 17 patients were included in the study, 10 were treated with the combined method and 7 with NPWT. Patients were followed for 6 weeks, with a final assessment at 3 months. Clinical improvement, microbiologic data, and toxicity of silver were evaluated. The antibacterial effects of ionic silver together with the development of granulation tissue promoted by NPWT reduced significantly the median extension of the wound between weeks 3 and 6 of treatment. The combination with silver also reduced bacterial colonization with Pseudomonas aeruginosa and the bacterial load on the surface of the wound. The silver levels correlated positively with the extension of the wound, although in none of the patients' toxic levels were reached. The combination of NPWT with nanocrystalline silver dressings was safe and as effective as NPWT alone. © 2015 by the Wound Healing Society.

Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

PubMed

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

2016-07-19

The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

An urgent need to reassess the safe levels of copper in the drinking water: lessons from studies on healthy animals harboring no genetic deficits.

PubMed

Pal, Amit; Jayamani, Jayagandan; Prasad, Rajendra

2014-09-01

Recent seminal studies have established neurodegeneration, cognitive waning and/or β-amyloid deposition due to chronic copper intoxication via drinking water in healthy animals; henceforth, fuelling the debate all again over the safe levels of copper in the drinking water. This review encompasses the contemporary imperative animal studies in which the effect of chronic copper toxicity (especially via drinking water) was evaluated on the central nervous system and memory of uncompromised animals along with discussing the future perspectives. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

Background: In general, organic solvents are inhibiting many physiological enzymes and alter the behavioural functions, but the available scientific knowledge on laboratory solvent induced organ specific toxins are very limited. Hence, the present study was planned to determine the sub-chronic toxic effects of petroleum ether (boiling point 40–60°C), a laboratory solvent in Sprague-Dawley (SD) rats. Materials and Methods: The SD rats were divided into three different groups viz., control, low exposure petroleum ether (250 mg/kg; i.p.) and high exposure petroleum ether (500 mg/kg; i.p.) administered group. The animals were exposed with petroleum ether once daily for 2 weeks. Prior to the experiment and end of the experiment animals behaviour, locomotor and memory levels were monitored. Before initiating the study animals were trained for 2 weeks for its learning process and its memory levels were evaluated. Body weight (BW) analysis, locomotor activity, anxiogenic effect (elevated plus maze) and learning and memory (Morris water navigation task) were monitored at regular intervals. On 14th day of the experiment, few ml of blood sample was collected from all the experimental animals for estimation of biochemical parameters. At the end of the experiment, all the animals were sacrificed, and brain, liver, heart, and kidney were collected for biochemical and histopathological analysis. Results: In rats, petroleum ether significantly altered the behavioural functions; reduced the locomotor activity, grip strength, learning and memory process; inhibited the regular body weight growth and caused anxiogenic effects. Dose-dependent organ specific toxicity with petroleum ether treated group was observed in brain, heart, lung, liver, and kidney. Extrapyramidal effects that include piloerection and cannibalism were also observed with petroleum ether administered group. These results suggested that the petroleum ether showed a significant decrease in central nervous system (CNS) activity, and it has dose-dependent toxicity on all vital organs. Conclusion: The dose-dependent CNS and organ specific toxicity was observed with sub-chronic administration of petroleum ether in SD rats. PMID:25316988

USE OF MODELS TO SUPPORT WATER QUALTIY CRITERIA - A CASE STUDY

EPA Science Inventory

In the United States, current methods for deriving chemical criteria protective of aquatic life depend on acute and chronic toxicity test results involving several species. These results are analyzed statistically to identify chemical concentrations that protect the majority of ...

Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

2016-02-01

Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle.

PubMed

Emmett, Michael

2014-01-01

The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes.

Treatment of chronically digoxin-poisoned patients with a newer digoxin immune fab--a retrospective study.

PubMed

Schaeffer, Tammi H; Mlynarchek, Sara L; Stanford, Christopher F; Delgado, João; Holstege, Christopher P; Olsen, Dean; Bogdan, Gregory M

2010-10-01

Digoxin is used in the treatment of patients with cardiac dysfunction, though toxicity sometimes results from the use of this medication. In 1986, the US Food and Drug Administration (FDA) approved a digoxin immune Fab for the treatment of such patients. In 2001, the FDA approved a newer digoxin immune Fab, a digoxin-specific antibody (DSAb) known as DigiFab (Protherics Inc, Brentwood, Tennessee), though minimal literature exists on the clinical effects of this DSAb. To characterize a cohort of patients presenting with chronic digoxin toxicity and to describe the clinical course of these patients with the use of DSAb. A retrospective study included patients with life-threatening cardiotoxicity and serum digoxin level greater than 2 ng/mL who were treated at two US hospitals from 2003 to 2006. Trained investigators abstracted data from patients' medical records and assessed changes in clinical and laboratory parameters at regular intervals (0-4, >4-12, >12-24, and >24-72 hours) after treatment with DSAb. An expert panel reviewed electrocardiogram results to identify life-threatening manifestations of digoxin toxicity before and after DSAb treatment. Efficacy of treatment was assessed as rates of improvement in clinical parameters and cardiotoxic effects. Rates of adverse drug reactions were used to characterize safety. All data were analyzed with descriptive statistics. Fourteen patients (mean [SD] age, 71.3 [10.4] years) were treated for chronic digoxin toxicity. At presentation, 12 patients had a heart rate of less than 45 beats per minute, 1 had third-degree heart block, and 1 had asystole. Mean serum digoxin level was 3.6 ng/mL. Eleven patients had abnormal renal function. After administration of DSAb, clinical parameters improved in all patients. Within 24 hours, cardiotoxicity resolved in 7 of 9 evaluable patients. Two adverse drug reactions possibly related to DigiFab occurred, both of which resolved with conventional measures. Two patients died from conditions unrelated to treatment. The newer DSAb appears to be a safe and effective treatment for resolving digoxin toxicity in adults, as indicated by electrocardiogram and clinical assessments. Because patients with multiple comorbidities may be at greater risk for digoxin toxicity, they should be closely monitored during treatment with digoxin.

Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part III. Effluent Toxicity Tests

EPA Science Inventory

This paper reports on the results of chronic toxicity tests conducted with common surrogate species, and several threatened and endangered species for which there were excess artificially propagated stock to allow direct testing.

A BIOGENIC ROLE IN EXPOSURE TO TWO TOXIC COMPOUNDS

EPA Science Inventory

Biogenic sources play an important role in ozone and particulate concentrations through emissions of volatile organic compounds. The same emissions also contribute to chronic toxic exposures from formaldehyde and acetaldehyde because each compound arises through primary and se...

Acetaminophen hepatotoxicity in mice: Effect of age, frailty and exposure type

PubMed Central

Kane, Alice E.; Mitchell, Sarah J.; Mach, John; Huizer-Pajkos, Aniko; McKenzie, Catriona; Jones, Brett; Cogger, Victoria; Le Couteur, David G.; de Cabo, Rafael; Hilmer, Sarah N.

2018-01-01

Acetaminophen is a commonly used analgesic that can cause severe hepatotoxicity in overdose. Despite old age and frailty being associated with extensive and long-term utilization of acetaminophen and a high prevalence of adverse drug reactions, there is limited information on the risks of toxicity from acetaminophen in old age and frailty. This study aimed to assess changes in the risk and mechanisms of hepatotoxicity from acute, chronic and sub-acute acetaminophen exposure with old age and frailty in mice. Young and old male C57BL/6 mice were exposed to either acute (300 mg/kg via oral gavage), chronic (100 mg/kg/day in diet for six weeks) or sub-acute (250 mg/kg, t.i.d., for three days) acetaminophen, or saline control. Pre-dosing mice were scored for the mouse clinical frailty index, and after dosing serum and liver tissue were collected for assessment of toxicity and mechanisms. There were no differences with old age or frailty in the degree of hepatotoxicity induced by acute, chronic or subacute acetaminophen exposure as assessed by serum liver enzymes and histology. Age-related changes in the acetaminophen toxicity pathways included increased liver GSH concentrations, increased NQO1 activity and an increased pro- and anti-inflammatory response to acetaminophen in old age. Frailty-related changes included a negative correlation between frailty index and serum protein, albumin and ALP concentrations for some mouse groups. In conclusion, although there were changes in some pathways that would be expected to influence susceptibility to acetaminophen toxicity, there was no overall increase in acetaminophen hepatotoxicity with old age or frailty in mice. PMID:26615879

Immune Regulation during Chronic Visceral Leishmaniasis

PubMed Central

Faleiro, Rebecca J.; Kumar, Rajiv; Hafner, Louise M.; Engwerda, Christian R.

2014-01-01

Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed. PMID:25010815

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5- Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 6. Volume 1

DTIC Science & Technology

1984-04-01

incidence of liver tumo-s. On reanalysis female mice receiving 35 mg/kg/day did not show a significant increase in hepatocarcinomas (Table 46). o The... hepatocarcinomas , A p valu(e of = 0.09 was, however, seen for 175/100 mg/kg/day-treated females when compared to historical controls. The small number of

[Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers].

PubMed

Shilov, V V; Siurin, S A

2015-01-01

Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation.

A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo.

PubMed

Das, Banibrata; Rajagopalan, Subramanian; Joshi, Gnanada S; Xu, Liping; Luo, Dan; Andersen, Julie K; Todi, Sokol V; Dutta, Aloke K

2017-09-01

Here, we report the characterization of a novel hybrid D 2 /D 3 agonist and iron (II) specific chelator, D-607, as a multi-target-directed ligand against Parkinson's disease (PD). In our previously published report, we showed that D-607 is a potent agonist of dopamine (DA) D 2 /D 3 receptors, exhibits efficacy in a reserpinized PD animal model and preferentially chelates to iron (II). As further evidence of its potential as a neuroprotective agent in PD, the present study reveals D-607 to be protective in neuronal PC12 cells against 6-OHDA toxicity. In an in vivo Drosophila melanogaster model expressing a disease-causing variant of α-synuclein (α-Syn) protein in fly eyes, the compound was found to significantly suppress toxicity compared to controls, concomitant with reduced levels of aggregated α-Syn. Furthermore, D-607 was able to rescue DAergic neurons from MPTP toxicity in mice, a well-known PD neurotoxicity model, following both sub-chronic and chronic MPTP administration. Mechanistic studies indicated that possible protection of mitochondria, up-regulation of hypoxia-inducible factor, reduction in formation of α-Syn aggregates and antioxidant activity may underlie the observed neuroprotection effects. These observations strongly suggest that D-607 has potential as a promising multifunctional lead molecule for viable symptomatic and disease-modifying therapy for PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sublethal and Reproductive Effects of Acute and Chronic Exposure to Flowback and Produced Water from Hydraulic Fracturing on the Water Flea Daphnia magna.

PubMed

Blewett, Tamzin A; Delompré, Perrine L M; He, Yuhe; Folkerts, Erik J; Flynn, Shannon L; Alessi, Daniel S; Goss, Greg G

2017-03-07

Hydraulic fracturing is an industrial process allowing for the extraction of gas or oil. To fracture the rocks, a proprietary mix of chemicals is injected under high pressure, which later returns to the surface as flowback and produced water (FPW). FPW is a complex chemical mixture consisting of trace metals, organic compounds, and often, high levels of salts. FPW toxicity to the model freshwater crustacean Daphnia magna was characterized utilizing acute (48 h median lethal concentrations; LC 50 ) and chronic (21 day) exposures. A decrease in reproduction was observed, with a mean value of 18.5 neonates produced per replicate over a 21 day chronic exposure to 0.04% FPW, which was a significant decrease from the average of 64 neonates produced in the controls. The time to first brood was delayed in the highest FPW (0.04%) treatment. Neonates exhibited an LC 50 of 0.19% of full-strength FPW, making them more sensitive than adults, which displayed an LC 50 value of 0.75%. Quantitative PCR highlighted significant changes in expression of genes encoding xenobiotic metabolism (cyp4) and moulting (cut). This study is the first to characterize chronic FPW toxicity and will help with the development of environmental monitoring and risk assessment of FPW spills.

Toxic metals in tissues of fishes from the Black Sea and associated human health risk exposure.

PubMed

Plavan, Gabriel; Jitar, Oana; Teodosiu, Carmen; Nicoara, Mircea; Micu, Dragos; Strungaru, Stefan-Adrian

2017-03-01

The anthropogenic activities in the Black Sea area are responsible for toxic metal contamination of sea food products. In this study, several toxic metals: cadmium, lead, nickel, chromium, and copper were quantified in different tissues (digestive tract, muscle, skeleton, skin) of nine fish species (Neogobius melanostomus, Belone belone, Solea solea, Trachurus mediterraneus ponticus, Sardina pilchardus, Engraulis encrasicolus, Pomatomus saltatrix, Sprattus sprattus, Scorpaena porcus) by using atomic absorption spectrometer with a high-resolution continuum source and graphite furnace technique (HR-CS GF-AAS), and the risk of fish meat consumption by the young human population was evaluated. These metals are used in high amounts in industries located near the coastline such as shipyard construction and industrial plants. Toxic metal accumulation depends on fish feeding behavior, abiotic conditions, metal chemistry, and animal physiology. For instance, cadmium was measured in the muscle of the investigated species and average values of 0.0008-0.0338 mg kg -1 were obtained. The lowest average value of this metal was measured at benthic species N. melanostomus and the highest at the pelagic predator T. mediterraneus ponticus. Generally, the highest metal concentration was measured in the digestive tract that has the role of biofilter for these contaminants. The risk of contamination is significantly reduced by avoiding the consumption of certain fish tissues (digestive tract and skin for copper and skeleton for nickel). An estimation of the dietary metal intake to young consumers was realized for each of the studied species of fish from Romanian, Bulgarian, and Turkish waters, during the period 2001-2014 in order to evaluate the risks of chronic exposure in time due to metal toxicity. This estimation is important for the prevention of chronic exposure due to metal toxicity. Food exposure to studied metals showed a negative trend for Romania, Turkey, and Bulgaria based on the data provided by this study. The young consumers were highly exposed to these elements during the 2001-2006 period as proven by the results from this study.

Different influences of field aging on nickel toxicity to Folsomia candida in two types of soil.

PubMed

Liu, Yu-Rong; Li, Jing; He, Ji-Zheng; Ma, Yi-Bing; Zheng, Yuan-Ming

2015-06-01

Metal aging in soils has been considered an important factor influencing its availability and toxicity to organisms. In this study, we report the influence of 5 years field aging on the nickel (Ni) toxicity to collembolan Folsomia candida based on two different types of soil from Dezhou (DZ) and Qiyang (QY) counties in China. Acute and chronic toxicity of Ni to F. candida was assessed in both freshly spiked and field aging contaminated soils. We found that 5 years field aging increased the EC50 and 2d-LC50 values of Ni to F. candida in the DZ soil, while little influence on the Ni toxicity was observed in the QY soil. There was no adverse effect of the long-term field aging on the Ni toxicity to the survival of F. candida in the two tested soils. In addition, field aging of the two soils impacted differently the water-soluble Ni concentrations, which were significantly correlated to the juvenile production of F. candida based on a logistic model. Our study highlights different effects of long-term field aging on the Ni toxicity to F. candida between divergent types of soil, and this should be taken into account in future toxicity testing and risk assessment practices.

CHRONIC DOSE RESPONSE STUDY OF LEAD TOXICITY IN RATS: ASSIGNMENT OF A LOWEST OBSERVED EFFECT LEVEL IN A DRINKING WATER STUDY. (R827161)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

[Effects of rare earth elements on soil fauna community structure and their ecotoxicity to Holotrichia parallela].

PubMed

Li, Guiting; Jiang, Junqi; Chen, Jie; Zou, Yunding; Zhang, Xincai

2006-01-01

By the method of OECD filter paper contact, this paper studied the effects of applied rare earth elements on soil fauna community structure and their ecological toxicity to Holotrichia parallela in bean field. The results showed that there were no significant differences between the treatments and the control in soil fauna species, quantity of main species, and diversity index. Urgent and chronic toxic test showed that the differences between the treatments and the control were not significant. It was suggested that within the range of test dosages, rare earth elements had little ecological toxicity to Holotrichia parallela, and did not change the soil fauna community structure.

TOXICITY OF PENTACHLOROPHENOL TO ENDANGERED AND SURROGATE FISH SPECIES

EPA Science Inventory

Water quality criteria (WQC) generally are based on the responses of easily cultured and tested surrogate species. Little is known about the relative sensitivity of surrogate and endangered species. The objective of this study was to compare acute and chronic (early life-stage) ...

HEALTH EFFECTS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA

EPA Science Inventory

Arsenite and arsenate are widely present in natural waters. The inorganic forms , especially arsenite, are believed to be the most toxic species. Methylation is often considered to be the primary detoxification pathway for the metaboliism of inorganic arsenic. Recently studi...

Draft Test Guideline: Daphnid Chronic Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Mysid Chronic Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

HALOACETONITRILES VS. REGULATED HALOACETIC ACIDS: ARE NITROGEN CONTAINING DBPS MORE TOXIC?

EPA Science Inventory

Haloacetonitriles (HANs) are toxic nitrogenous drinking water disinfection by-products (N-DBPs) and are observed with chlorine, chloramine, or chlorine dioxide disinfection. Using microplate-based Chinese hamster ovary (CHO) cell assays for chronic cytotoxicity and acute genotoxi...

Adaptation of rat gastric tissue against indomethacin toxicity.

PubMed

Polat, Beyzagul; Suleyman, Halis; Alp, Hamit Hakan

2010-06-07

Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro-toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/-3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX-2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Hormetic effect of methylmercury on Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmcke, Kirsten J., E-mail: Kirsten.J.Helmcke@gmail.com; Aschner, Michael, E-mail: Michael.Aschner@vanderbilt.ed

2010-10-15

Research has demonstrated the toxic effects of methylmercury (MeHg), yet molecular mechanisms underlying its toxicity are not completely understood. Caenorhabditis elegans (C. elegans) offers a unique biological model to explore mechanisms of MeHg toxicity given many advantages associated with its ease of use and genetic power. Since our previous work indicated neurotoxic resistance of C. elegans to MeHg, the present study was designed to examine molecular mechanisms associated with this resistance. We hypothesized MeHg would induce expression of gst, hsp or mtl in vivo since glutathione (GSH), heat shock proteins (HSPs), and metallothioneins (MTs) have shown involvement in MeHg toxicity.more » Our studies demonstrated a modest, but significant increase in fluorescence in gst-4::GFP and mtl-1::GFP strains at an acute, low L1 MeHg exposure, whereas chronic L4 MeHg exposure induced expression of gst-4::GFP and hsp-4::GFP. Knockout gst-4 animals showed no alterations in lethality sensitivity compared to wildtype animals whereas mtl knockouts displayed increased sensitivity to MeHg exposure. GSH levels were increased by acute MeHg treatment and depleted with chronic exposure. We also demonstrate that MeHg induces hormesis, a phenotype whereby a sublethal exposure to MeHg rendered C. elegans resistant to subsequent exposure to the organometal. The involvement of gst-4, hsp-4, mtl-1, and mtl-2 in hormesis was examined. An increase in gst-4::GFP expression after a low-dose acute exposure to MeHg indicated that gst-4 may be involved in this response. Our results implicate GSH, HSPs, and MTs in protecting C. elegans from MeHg toxicity and show a potential role of gst-4 in MeHg-induced hormesis.« less

Toxicity identification evaluation of cosmetics industry wastewater.

PubMed

de Melo, Elisa Dias; Mounteer, Ann H; Leão, Lucas Henrique de Souza; Bahia, Renata Cibele Barros; Campos, Izabella Maria Ferreira

2013-01-15

The cosmetics industry has shown steady growth in many developing countries over the past several years, yet little research exists on toxicity of wastewaters it generates. This study describes a toxicity identification evaluation conducted on wastewater from a small Brazilian hair care products manufacturing plant. Physicochemical and ecotoxicological analyses of three wastewater treatment plant inlet and outlet samples collected over a six month period revealed inefficient operation of the treatment system and thus treated wastewater organic matter, suspended solids and surfactants contents consistently exceeded discharge limits. Treated wastewater also presented high acute toxicity to Daphnia similis and chronic toxicity to Ceriodaphnia dubia and Pseudokirchneriella subcapitata. This toxicity was associated with suspended solids, volatile or sublatable and non-polar to moderately polar organic compounds that could be recovered in filtration and aeration residues. Seven surfactants used in the largest quantities in the production process were highly toxic to P. subcapitata and D. similis. These results indicated that surfactants, important production raw materials, are a probable source of toxicity, although other possible sources, such as fragrances, should not be discarded. Improved treatment plant operational control may reduce toxicity and lower impact of wastewater discharge to receiving waters. Copyright © 2012 Elsevier B.V. All rights reserved.

Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury

PubMed Central

Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

2014-01-01

The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of physiological cytoprotective factors in nonparenchymal liver cells. Such drug-induced release of endogenous cytoprotectants will advance therapeutic development for hepatic injury. PMID:24220607

Enhancement of parathion toxicity to quail by heat and cold exposure

USGS Publications Warehouse

Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.

1987-01-01

Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26.degree. C) or exposed to elevated (37.degree. C) or reduced (4.degree. C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a two-fold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26.degree. C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., < 10% versus 48% depression after 24 hr). Increased liver weight and a doubling of paraoxonase activity may have been associated with greater tolerance to sublethal doses of parathion in chronically cold-exposed quail. These findings, together with limited field observations, indicate that the hazard associated with anticholinesterase exposure of wild birds is substantially influenced by environmental temperature.

Monitoring of toxicity of As(V) solutions by AMPHITOX test without and with treatment with zerovalent iron nanoparticles.

PubMed

Pérez Coll, Cristina S; Pabón-Reyes, Carolina; Meichtry, Jorge M; Litter, Marta I

2018-06-01

Changes in toxicity of As(V) solutions from acute to chronic exposure have been evaluated by the AMPHITOX test. This test employs Rhinella arenarum, a widely distributed toad in Argentine areas. LOEC values were 6.37 and 1.88 mg L -1 for embryos and larvae, respectively, and serious sublethal effects have been observed. Toxicity of As(V) solutions has been also evaluated after treatment with zerovalent iron nanoparticles (nZVI). After 60 min of treatment with nZVI, As(V) removal was 77%, and neither lethal nor sublethal effects were observed. However, nZVI had to be eliminated before the bioassay because they caused adverse effects in both embryos and larvae. This work highlights the high sensitivity of R. arenarum to As(V), the relevance to assess toxicity on different periods of the lifecycle, and the need to expand exposure to As(V) to chronic times. The utility of the test for monitoring toxicity changes in As(V) solutions after nZVI treatment has been also shown. Copyright © 2018 Elsevier B.V. All rights reserved.

Appendix E. Analysis of Chronic Toxicity Data and Acute Chronic Ratios (ACRs) in Support of Deriving Chronic HC5s: Acetylcholinesterase Inhibitors

EPA Science Inventory

The analysis described in this appendix is one of several conducted in support of developing a common methodology for assessing chemical effects on aquatic animals for use by the USEPA Office of Pesticide Programs (OPP) and the Office of Water (OW). Other appendices describe met...

Temporal assessment of copper speciation, bioavailability and toxicity in UK freshwaters using chemical equilibrium and biotic ligand models: Implications for compliance with copper environmental quality standards.

PubMed

Lathouri, Maria; Korre, Anna

2015-12-15

Although significant progress has been made in understanding how environmental factors modify the speciation, bioavailability and toxicity of metals such as copper in aquatic environments, the current methods used to establish water quality standards do not necessarily consider the different geological and geochemical characteristics of a given site and the factors that affect copper fate, bioavailability potential and toxicity. In addition, the temporal variation in the concentration and bioavailable metal fraction is also important in freshwater systems. The work presented in this paper illustrates the temporal and seasonal variability of a range of water quality parameters, and Cu speciation, bioavailability and toxicity at four freshwaters sites in the UK. Rivers Coquet, Cree, Lower Clyde and Eden (Kent) were selected to cover a broad range of different geochemical environments and site characteristics. The monitoring data used covered a period of around six years at almost monthly intervals. Chemical equilibrium modelling was used to study temporal variations in Cu speciation and was combined with acute toxicity modelling to assess Cu bioavailability for two aquatic species, Daphnia magna and Daphnia pulex. The estimated copper bioavailability, toxicity levels and the corresponding ecosystem risks were analysed in relation to key water quality parameters (alkalinity, pH and DOC). Although copper concentrations did not vary much during the sampling period or between the seasons at the different sites; copper bioavailability varied markedly. In addition, through the chronic-Cu BLM-based on the voluntary risk assessment approach, the potential environmental risk in terms of the chronic toxicity was assessed. A much higher likelihood of toxicity effects was found during the cold period at all sites. It is suggested that besides the metal (copper) concentration in the surface water environment, the variability and seasonality of other important water quality parameters should be considered in setting appropriately protective environmental quality standards for metals. Copyright © 2015 Elsevier B.V. All rights reserved.

Advances in understanding the response of fish to linear alcohols in the environment.

PubMed

Belanger, Scott E; Rawlings, Jane M; Stackhouse, Ricky

2018-09-01

Short to long chain alcohols have a range of ecotoxicity to aquatic life driven by hydrophobic interactions with biological membranes. Carbon chain length and octanol:water partitioning coefficients are surrogates for hydrophobicity and strongly relate to aquatic toxicity. In these investigations, the toxicity of ethanol to 1-n-dodecanol to juvenile fish in standard acute toxicity tests is reviewed. Toxicity tests employing fish embryos (zebrafish Danio rerio and fathead minnow Pimephales promelas) in the Fish Embryo Test (OECD 236) format were conducted from C2 to C10 to compare against standard juvenile fish toxicity. Quantitative structure activity relationships for FET and fish individually and combined demonstrate that embryos are not different in sensitivity to juvenile fish. A combined QSAR was developed of the form Log 96 h LC50 (mM/L) = -0.925*log Kow + 2.060 (R2 10 = 0.954). Alcohols of 11-12 carbons show a deflection in the QSAR as toxicity approaches the solubility limit. Alcohols with longer chain lengths may only be tested at lower exposures relevant for chronic toxicity. Decanol was evaluated in a 33-d fish early life stage test (OECD 210) and survival was the most sensitive endpoint (EC10 = 0.43 mg/L, 0.0027 mM/L). This study suggests a reasonable acute to chronic ratio of 6.5 in line with historical literature for non-polar narcotic compounds. Fish are not uniquely more sensitive than Daphnia magna which suggests estimations of environmental hazard can be confidently made with either taxon. The overall environmental risk assessments for the longer chain alcohols included in this research remain largely unchanged primarily due to previous research demonstrating a very minimal environmental exposure even for highly toxic members of the category. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and non-tobacco products.

PubMed

Kaur, Gurjot; Muthumalage, Thivanka; Rahman, Irfan

2018-05-15

Tobacco products containing flavorings, such as electronic nicotine delivery devices (ENDS) or e-cigarettes, cigars/cigarillos, waterpipes, and heat-not-burn devices (iQOS) are continuously evolving. In addition to increasing the exposure of teenagers and adults to nicotine containing flavoring products and flavoring enhancers, chances of nicotine addiction through chronic use and abuse also increase. These flavorings are believed to be safe for ingestion, but little information is available about their effects on the lungs. In this review, we have discussed the in vitro and in vivo data on toxicity of flavoring chemicals in lung cells. We have further discussed the common flavoring agents, such as diacetyl and menthol, currently available detection methods, and the toxicological mechanisms associated with oxidative stress, inflammation, mucociliary clearance, and DNA damage in cells, mice, and humans. Finally, we present potential biomarkers that could be utilized for future risk assessment. This review provides crucial parameters important for evaluation of risk associated with flavoring agents and flavoring enhancers used in tobacco products and ENDS. Future studies can be designed to address the potential toxicity of inhaled flavorings and their biomarkers in users as well as in chronic exposure studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of ranitidine and its photoderivatives in the aquatic environment.

PubMed

Isidori, Marina; Parrella, Alfredo; Pistillo, Paola; Temussi, Fabio

2009-07-01

This study was designed to assess the overall ecotoxicity of ranitidine, a histamine H(2)-receptor antagonist that inhibits stomach acid production. Hence, in addition to ranitidine, its main two photoderivatives, obtained by solar simulator irradiation in water, were investigated. The photoproducts were identified by their physical features. Bioassays were performed on rotifers and microcrustaceans to assess acute and chronic toxicity, while SOS Chromotest and Ames test were utilized to detect the genotoxic potential of the investigated compounds. The results showed that ranitidine did not show any acute toxicity at the highest concentration tested (100 mg/L) for all the organisms utilized in the bioassays. Chronic exposure to these compounds caused inhibition of growth population on rotifers and crustaceans. Genotoxic and mutagenic effects were especially found for one photoproduct suggesting that transformation products, as frequently demonstrated, may show effects higher than the respective parental compound.

Prevention and treatment of Nitrite toxicity in juvenile steelhead trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary A.; Yasutake, W.T.

1978-01-01

The efficacy of mineral salts, pH, and tetramethylthianine (methylene blue) treatment in reducing the acute toxicity of nitrite to fingerling steelhead trout (Salmo gairdneri) was determined using a static bioassay system at 10 °C. The acute toxicity (96-h LC50) was reduced by a factor of about 24 for 5-g steelhead and 13 for 10-g fish when the total water hardness was increased from 25 to 300 mg/L (as CaCO3). NaCl or CaCl2 additions (0–200 mg/L) reduced toxicity by a factor of up to 3 for NaCl and 50 for CaCl2. Increasing the pH from 6.0 to 8.0 decreased toxicity by a factor of about 8 for the smaller and 3 for the larger fish. Methylene blue at 0.1 or 1.0 mg/L was effective in decreasing acute toxicity. For alleviating methemoglobinemia, removing the fish to freshwater for 48 h was about as effective as 1.0 mg/L methylene blue. Chronic exposure in soft water to 0.03 mg/L NO2-N for 6 mo caused no significant growth reduction, gill histological changes, hematological dyscrasias, or impaired ability of the smolts to adapt to 30‰ seawater and grow for an additional 2 mo. Key words: nitrite, toxicity, fish, methylene blue, pH, salts, acute toxicity, chronic toxicity

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

PubMed

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

A32A-0126: A BIOGENIC ROLE IN EXPOSURE TO TWO TOXIC COMPOUNDS

EPA Science Inventory

Biogenic sources play an important role in ozone and particulate concentrations through emissions of volatile organic compounds. The same emissions also contribute to chronic toxic exposures from formaldehyde and acetaldehyde because each compound arises through primary and sec...

TOXICITY TESTING, RISK ASSESSMENT, AND OPTIONS FOR DREDGED MATERIAL MANAGEMENT

EPA Science Inventory

Programs for evaluating proposed discharges of dredged material into waters of the United States specify a tiered testing and evaluation protocol that includes performance of acute and chronic bioassays to assess toxicity of the dredged sediments. Although these evaluations refl...

TROPICAL COLLECTOR URCHIN, TRIPNEUSTES GRATILLA, FERTILIZATION TEST METHOD

EPA Science Inventory

This document describes a fertilization method to estimate the chronic toxicity of effluents and receiving waters to the gametes of the tropical sea urchin (Tripneustes gratilla). This toxicity test measures the fertilizing capacity of sperm following a static, non-renewal 60-mi...

Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the B6C3F1 Hybrid Mouse). Volume 1

DTIC Science & Technology

1984-12-01

chemistry parameters (see section l1.D.) Results of pretreatment health screen were within limits for the mice of this strain and age. Microbiological ...negative as measured by Microbiological Associates, Bethesda MD. Animals received 5002 rodent chow from arrival urtil their termina~lon, except during a...CARCINOGENICITY STUDY OF FRINITROTOLUENE IN THE B6C3FI MOUSE. ’EST DIET CONCENTRATION OF TNT TESI DOSE % % A x 100 - K!E!Th (mg,/kg/day) SEX INTENDED ANALYSED REL

Three studies using Ceriodaphnia to detect nonpoint sources of metals from mine drainage

USGS Publications Warehouse

Nimmo, Del Wayne R.; Dodson, Max H.; Davies, Patrick H.; Greene, Joseph C.; Kerr, Mark A.

1990-01-01

Since its introduction, Ceriodaphnia dubia, a small planktonic daphnid, has been widely used for biomonitoring point source discharges. This species was also used to determine nonpoint sources of metals and related contaminants in three trout streams in the west where mining activities have been widespread. Along Chalk Creek, Colo., specific tailings (and impacted tributaries) were sources of metals toxic to fish using the water in a hatchery. At stations below extensive mine tailings in the upper Clark Fork River, Mont., drainage was acutely and chronically toxic to daphnids and paralleled reduced or nonexistent populations of trout. In Whitewood Creek, S. Dak., reduced toxicity below a gold mine portended that fish could live in the stream segment previously impaired by the mine. Toxicity downstream revealed a previously unknown nonpoint source of chromium.

40 CFR 799.9410 - TSCA chronic toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... should be used, if possible, throughout the duration of the study, and the research sample should be... continuously or intermittently depending on the method of analysis. Chamber concentration may be measured using gravimetric or analytical methods, as appropriate. If trial run measurements are reasonably consistent (±10...

40 CFR 799.9410 - TSCA chronic toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... should be used, if possible, throughout the duration of the study, and the research sample should be... continuously or intermittently depending on the method of analysis. Chamber concentration may be measured using gravimetric or analytical methods, as appropriate. If trial run measurements are reasonably consistent (±10...

40 CFR 799.9410 - TSCA chronic toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... should be used, if possible, throughout the duration of the study, and the research sample should be... continuously or intermittently depending on the method of analysis. Chamber concentration may be measured using gravimetric or analytical methods, as appropriate. If trial run measurements are reasonably consistent (±10...

40 CFR 799.9410 - TSCA chronic toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... should be used, if possible, throughout the duration of the study, and the research sample should be... continuously or intermittently depending on the method of analysis. Chamber concentration may be measured using gravimetric or analytical methods, as appropriate. If trial run measurements are reasonably consistent (±10...

40 CFR 799.9410 - TSCA chronic toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... should be used, if possible, throughout the duration of the study, and the research sample should be... continuously or intermittently depending on the method of analysis. Chamber concentration may be measured using gravimetric or analytical methods, as appropriate. If trial run measurements are reasonably consistent (±10...

Pulmonary Sensitivity to Ozone Exposure in Sedentary Versus Chronically Trained, Female Rats

EPA Science Inventory

Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility to some environmental toxicants. The lack of adequate exercise combined with poor dietary choices are considered to be primary causes of obesity. To study the impact of an active ve...

DEVELOPMENT OF A FATHEAD MINNOW MODEL FOR EVALUATING EXPOSURE OF FISH TO GENOTOXIC SUBSTANCES

EPA Science Inventory

The fathead minnow (FHM) is widely used as a standard test species for acute and chronic toxicity testing of contaminants, effluents, and receiving waters. Because of its widespread distribution throughout North America, this species also has application in monitoring studies and...

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia

PubMed Central

Barrientos, Jacqueline C.; Barr, Paul M.; Flinn, Ian W.; Burger, Jan A.; Tran, Anh; Clow, Fong; James, Danelle F.; Graef, Thorsten; Friedberg, Jonathan W.; Rai, Kanti; O’Brien, Susan

2015-01-01

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. PMID:25755291

Characterisation and toxicological assessment of Neutral Methacrylate Copolymer for GRAS evaluation.

PubMed

Eisele, Johanna; Haynes, Geoff; Kreuzer, Knut; Rosamilia, Tiana

2013-12-01

Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the pharmaceutical industry to permit pH-independent delayed release of active ingredients from oral dosage forms. This function has potential use with food supplements and this article describes available information on the safety of the substance. Oral administration of radiolabelled copolymer to rats resulted in the detection of chemically unchanged copolymer in the faeces, with negligible absorption. Safety studies revealed no adverse toxicity following repeated administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no evidence of genotoxicity, has low acute toxicity and no irritation or sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two alternative approaches. Daily exposure from use in dietary supplements is estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There would therefore appear to be no safety concerns under the intended conditions of use. The information provided is intended to support an evaluation that the substance may be "generally recognized as safe" (GRAS). Copyright © 2013 Elsevier Inc. All rights reserved.

Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years.

PubMed

Stout, M D; Nyska, A; Collins, B J; Witt, K L; Kissling, G E; Malarkey, D E; Hooth, M J

2009-04-01

Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice.

Chronic Toxicity and Carcinogenicity Studies of Chromium Picolinate Monohydrate Administered in Feed to F344/N Rats and B6C3F1 Mice for 2 Years

PubMed Central

Stout, M.D.; Nyska, A.; Collins, B.J.; Witt, K.L.; Kissling, G.E.; Malarkey, D.E.; Hooth, M.J.

2009-01-01

Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2,000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice. PMID:19166900

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia.

PubMed

Brown, Jennifer R; Barrientos, Jacqueline C; Barr, Paul M; Flinn, Ian W; Burger, Jan A; Tran, Anh; Clow, Fong; James, Danelle F; Graef, Thorsten; Friedberg, Jonathan W; Rai, Kanti; O'Brien, Susan

2015-05-07

The safety and efficacy of ibrutinib, an oral inhibitor of Bruton tyrosine kinase, were evaluated with chemoimmunotherapy (CIT) in a multicenter phase 1b study. Patients with relapsed/refractory chronic lymphocytic leukemia received bendamustine and rituximab (BR) or fludarabine, cyclophosphamide, and rituximab (FCR) for up to 6 cycles with daily ibrutinib (420 mg) until progressive disease or unacceptable toxicity. Enrollment to FCR-ibrutinib closed early due to a lack of fludarabine-naïve previously treated patients. No patients treated with BR-ibrutinib (n = 30) or FCR-ibrutinib (n = 3) experienced prolonged hematologic toxicity in cycle 1 (primary end point). Tolerability was as expected with either CIT or single-agent ibrutinib. The overall response rate (ORR) with BR-ibrutinib was 93.3%, including 16.7% complete responses (CRs) initially, which increased to 40% with the extension period. Including 1 patient with partial response with lymphocytosis, the best ORR was 96.7%. Sixteen of 21 patients with baseline cytopenias had sustained hematologic improvement. At 12 and 36 months, 86.3% and 70.3% remained progression-free, respectively. All 3 patients treated with ibrutinib-FCR achieved CR. Ibrutinib may enhance CIT efficacy without additive toxicities, providing the rationale for studying this combination in an ongoing phase 3 trial. The study is registered to www.clinicaltrials.gov as #NCT01292135. © 2015 by The American Society of Hematology.

[Toxic nephropathy secondary to occupational exposure to metallic mercury].

PubMed

Voitzuk, Ana; Greco, Vanina; Caputo, Daniel; Alvarez, Estela

2014-01-01

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Toxicological study of the different organs of Corchorus olitorius L. plant with special reference to their cardiac glycosides content.

PubMed

Negm, S; El-Shabrawy, O; Arbid, M; Radwan, A S

1980-03-01

The acute toxicity of the alcoholic extracts of seeds, roots stems and leaves of the fully mature Corchorus olitorius L. plant was determined in mice by intraperitoneal injection. The cardiac glycosides content of each extract was estimated and the correlation between the two investigated parameters was established. The chronic toxicity of the alcoholic extract of the seeds was determined in term of its haematological and symptomatical effects on mice upon intraperitoneal injection for a period of two months.

Dosimetric and toxicity comparison between prone and supine position IMRT for endometrial cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beriwal, Sushil; Jain, Sheena K.; Heron, Dwight E.

2007-02-01

Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensity-modulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose-volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in themore » prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose-volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches.« less

Use of reconstituted waters to evaluate effects of elevated major ions associated with mountaintop coal mining on freshwater invertebrates

USGS Publications Warehouse

Kunz, James L.; Conley, Justin M.; Buchwalter, David B.; ,; Teresa, J.; Kemble, Nile E.; Wang, Ning; Ingersoll, Christopher G.

2013-01-01

In previous laboratory chronic 7-d toxicity tests conducted with the cladoceran Ceriodaphnia dubia, surface waters collected from Appalachian sites impacted by coal mining have shown toxic effects associated with elevated total dissolved solids (TDS). The objective of the present study was to evaluate the effects of elevated major ions in chronic laboratory tests with C. dubia (7-d exposure), a unionid mussel (Lampsilis siliquoidea; 28-d exposure), an amphipod (Hyalella azteca; 28-d exposure), and a mayfly (Centroptilum triangulifer; 35-d exposure) in 3 reconstituted waters designed to be representative of 3 Appalachian sites impacted by coal mining. Two of the reconstituted waters had ionic compositions representative of alkaline mine drainage associated with mountaintop removal and valley fill-impacted streams (Winding Shoals and Boardtree, with elevated Mg, Ca, K, SO4, HCO3), and a third reconstituted water had an ionic composition representative of neutralized mine drainage (Upper Dempsey, with elevated Na, K, SO4, and HCO3). The waters with similar conductivities but, with different ionic compositions had different effects on the test organisms. The Winding Shoals and Boardtree reconstituted waters were consistently toxic to the mussel, the amphipod, and the mayfly. In contrast, the Upper Dempsey reconstituted water was toxic to the mussel, the amphipod, and the cladoceran but was not toxic to the mayfly. These results indicate that, although elevated TDS can be correlated with toxicity, the specific major ion composition of the water is important. Moreover, the choice of test organism is critical, particularly if a test species is to be used as a surrogate for a range of faunal groups.

Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

USGS Publications Warehouse

Elskus, Adria A.

2012-01-01

Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to organic matter in sediment and soils, it is particularly important to determine their effects on freshwater mussels and other freshwater benthic invertebrates in contact with sediments, as available toxicity studies with pelagic species, mainly Daphnia magna, may not be representative of these benthic organisms. Finally, there is a critical need for studies of the chronic effects of fungicides on reproduction, immunocompetence, and ecosystem function; sublethal endpoints with population and community-level relevance.

A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice.

PubMed

Banerjee, P; Biswas, S J; Belon, P; Khuda-Bukhsh, A R

2007-09-01

Groundwater arsenic contamination has become a menacing global problem. No drug is available until now to combat chronic arsenic poisoning. To examine if a potentized homeopathic remedy, Arsenicum Album-200, can effectively combat chronic arsenic toxicity induced by repeated injections of Arsenic trioxide in mice, the following experimental design was adopted. Mice (Mus musculus) were injected subcutaneously with 0.016% arsenic trioxide at the rate of 1 ml/100 g body weight, at an interval of 7 days until they were killed at day 30, 60, 90 or 120 and were divided into three groups: (i) one receiving a daily dose of Arsenicum Album-200 through oral administration, (ii) one receiving the same dose of diluted succussed alcohol (Alcohol-200) and (iii) another receiving neither drug, nor succussed alcohol. The remedy or the placebo, as the case may be, was fed from the next day onwards after injection until the day before the next injection, and the cycle was repeated until the mice were killed. Two other control groups were also maintained: one receiving only normal diet, and the other receiving normal diet and succussed alcohol. Several toxicity assays, such as cytogenetical (chromosome aberrations, micronuclei, mitotic index, sperm head anomaly) and biochemical (acid and alkaline phosphatases, lipid peroxidation), were periodically made. Compared with controls, the drug fed mice showed reduced toxicity at statistically significant levels in respect of all the parameters studied, thereby indicating protective potentials of the homeopathic drug against chronic arsenic poisoning.

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test... (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2, C3, C4, C5, and C7.... Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E...

Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

PubMed

Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

2015-12-01

The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

Acetaminophen Toxicity and 5-Oxoproline (Pyroglutamic Acid): A Tale of Two Cycles, One an ATP-Depleting Futile Cycle and the Other a Useful Cycle

PubMed Central

2014-01-01

Summary The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes. PMID:24235282

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okunieff, Paul; Xu Jianhua; Hu Dongping

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 themore » 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.« less

Immobilized materials for removal of toxic metal ions from surface/groundwaters and aqueous waste streams.

PubMed

Zawierucha, Iwona; Kozlowski, Cezary; Malina, Grzegorz

2016-04-01

Heavy metals from industrial processes are of special concern because they produce chronic poisoning in the aquatic environment. More strict environmental regulations on the discharge of toxic metals require the development of various technologies for their removal from polluted streams (i.e. industrial wastewater, mine waters, landfill leachate, and groundwater). The separation of toxic metal ions using immobilized materials (novel sorbents and membranes with doped ligands), due to their high selectivity and removal efficiency, increased stability, and low energy requirements, is promising for improving the environmental quality. This critical review is aimed at studying immobilized materials as potential remediation agents for the elimination of numerous toxic metal (e.g. Pb, Cd, Hg, and As) ions from polluted streams. This study covers the general characteristics of immobilized materials and separation processes, understanding of the metal ion removal mechanisms, a review of the application of immobilized materials for the removal of toxic metal ions, as well as the impacts of various parameters on the removal efficiency. In addition, emerging trends and opportunities in the field of remediation technologies using these materials are addressed.

Acute and chronic toxicity of pesticides on tadpoles of Physalaemus cuvieri (Anura, Leptodactylidae).

PubMed

Wrubleswski, Juliana; Reichert, Francisco Wilson; Galon, Leandro; Hartmann, Paulo Afonso; Hartmann, Marilia Teresinha

2018-04-01

Brazil is the largest consumer of pesticides in the world. However, knowledge on how these pesticides affect wildlife is scarce. Among the vertebrates, amphibians are particularly important in research to assess the impact of pesticides because of the correlation between pesticide and the decline of these species. This study aimed to evaluate the acute and chronic toxicity of commercial formulations of pesticides, i.e., atrazine (herbicide), cypermethrin (insecticide), and tebuconazole (fungicide) in Physalaemus cuvieri tadpoles. Eggs were collected in nature and cultivated under controlled conditions in the laboratory. Toxicity tests were carried out under standard conditions to determine the lethal concentration (LC 50 ) after 96 h of exposure and to determine the effect of sublethal concentrations after 7 days. In addition, we performed swimming activity tests on tadpoles exposed to sublethal concentrations. The lethal concentration (LC 50 ) was 19.69 mg/L for atrazine, 0.24 mg/L for cypermethrin and 0.98 mg/L for tebuconazole. In the acute test, atrazine showed lower toxicity than cypermethrin and tebuconazole for P. cuvieri. Swimming activity was affected at sublethal doses of atrazine and cypermethrin, but was not after exposure to tebuconazole. Cypermethrin was the insecticide that most altered the swimming activity of the individuals tested. The risk evaluation analysis indicated risks for tadpoles exposed to three tested pesticides, specially cypermethrin.

Predicting acute and chronic effects of wood preservative products in Daphnia magna and Pseudokirchneriella subcapitata based on the concept of concentration addition.

PubMed

Coors, Anja; Weisbrod, Barbara; Schoknecht, Ute; Sacher, Frank; Kehrer, Anja

2014-02-01

The current European legislation requires that combined effects of the active substances and any substance of concern contained in biocidal products are taken into account in environmental risk assessment. The hypothesis whether the consideration of active substances together with all formulation additives that are labeled as presenting an environmental hazard is sufficient for a reliable environmental risk assessment was tested in the present study by investigating 3 wood preservative products. Relevant single substances in the products, some of their generic mixtures, the biocidal products themselves, and aqueous eluates prepared from the products (representing potential environmental mixtures) were tested for effects on algal growth and Daphnia acute immobilization as well as reproduction. Predictions for the products and the eluates were based on the concept of concentration addition and were mostly found to provide reliable or at least protective estimates for the observed acute and chronic toxicity of the mixtures. The mixture toxicity considerations also indicated that the toxicity of each product was dominated by just 1 of the components, and that assessments based only on the dominating substance would be similarly protective as a full-mixture risk assessment. Yet, there remained uncertainty in some cases that could be related to the toxicity of transformation products, the impact of unidentified formulation additives, or synergistic interaction between active substances and formulation additives. © 2013 SETAC.

The potential acute and chronic toxicity of cyfluthrin on the soil model organism, Eisenia fetida.

PubMed

Li, Lingling; Yang, Da; Song, Yufang; Shi, Yi; Huang, Bin; Bitsch, Annette; Yan, Jun

2017-10-01

In this study, the acute (72h and 14 d) and chronic (28 d and 8 weeks) effects of cyfluthrin on earthworms were evaluated across different endpoints, which are mortality, growth, reproduction and enzyme activities. Cyfluthrin was rated as moderately toxic in 72-h filter paper test and low toxic in 14-day soil test. The exposure of earthworms to cyfluthrin-polluted soil for 8 weeks showed that growth of earthworms was inhibited by cyfluthrin, cocoon production and hatching were inhibited by 20-60mg/kg cyfluthrin. Moreover, 28-day soil test on the responses of enzymes associated with antioxidation and detoxification showed that the activities of catalase (CAT) and glutathione S- transferase (GST) were initially increased by cyfluthrin at 5-20mg/kg, but reduced at 30-60mg/kg, peroxidase (POD) was increased by 26-102% by cyfluthrin in the early period, except 5mg/kg on day 7, and ethoxyresorufin-O-deethylase (EROD) was increased by 29-335% by cyfluthrin after 3 days. Cyfluthrin degraded with a half-life of 24.8-34.8 d, showing the inconsistency between the continuous toxic responses of earthworms and degradation of cyfluthrin in soil. The variable responses of these indexes indicated that different level endpoints should be jointly considered for better evaluation of the environmental risk of contaminants in soil. Copyright © 2017 Elsevier Inc. All rights reserved.

The use of Ampelisca abdita growth rate as an indicator of sediment quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weston, D.P.; Thompson, B.

1995-12-31

Acute lethal bioassays with amphipod crustaceans are routinely used to assess toxicity of bulk sediments. A study within the San Francisco Bay Regional Monitoring Program (RMP) is in progress to develop a chronic bioassay with the amphipod Ampelisca abdita, measuring both survivorship and growth rates. This approach is attractive because depression of growth rate is likely to be a more sensitive indicator of toxic effects than acute lethality, and natural populations of A. abdita exist throughout the Bay. Spiked sediment bioassays, using cadmium and crude oil, were used to demonstrate the relative sensitivity of the standard 10-day lethal test vs.more » the 30-day growth test. Sediments were also collected from 9 sites throughout the Bay, ranging from areas adjacent to municipal wastewater discharges to areas distant from known point source inputs. These samples were then split, and used for side-by-side comparison of acute (lethal) and chronic (growth) toxicity tests. Survivorship exceeded 90% in all tests, including those sediments collected nearest the wastewater outfalls. Growth rates were contrasted among the various treatments to examine the utility of this end point in discriminating the outfall sites. Data on the spatial distribution, abundance, and size-frequency distribution of native populations was examined within the context of using growth rate as an indicator of toxic effects in natural populations as well.« less

Sublethal effects of phenanthrene, nicotine, and pinane on Daphnia pulex

USGS Publications Warehouse

Savino, Jacqueline F.; Tanabe, Lila L.

1989-01-01

Chronic studies of Daphnia Pulex exposed to different concentrations of phenanthrene, nicotine, and pinane produced consistent sublethal effects among replicates and concentrations. The LOEC's for growth and fecundity with each chemical tested were 3 to 30% of the 48-hr EC50's. Growth decreased as concentration increased for each chemical tested, and fecundity approached zero at 2 to 5 times the LOEC for each chemical. In this study chemicals representing PAHs, heterocyclic nitrogen compounds, and cyclic alkanes, produced detectable sublethal effects in daphnids at less than 0.1 ppm in water. These chronic studies, in conjuction with the more extensive acute toxicity testing (Passino and Smith 1987; Perry and Smith 1988; Smith et al. 1988), provided a relatively quick but thorough toxicological assessment of a large array of chemicals and demonstrated the relative importance of different classes of compounds in changing growth and survival trends in given populations of native organisms. Classic toxicity tests continue to provide a reliable backdrop of results with which the effects of new chemicals or mixtures can be compared.

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna

2006-04-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 gmore » of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in combination with creatine and ascorbic acid on cancer-bearing animals had been investigated by measuring the increase in life span and tumor cell growth inhibition. The results indicated that anticancer effect of methylglyoxal was significantly augmented by ascorbic acid and further augmented by ascorbic acid and creatine. Nearly 80% of the animals treated with methylglyoxal plus ascorbic acid plus creatine were completely cured and devoid of any malignant cells within the peritoneal cavity.« less

AN EVALUATION OF THE 7-DAY TOXICITY TEST WITH AMERICAMYSIS BAHIA (FORMERLY MYSIDOPSIS BAHIA)

EPA Science Inventory

The 7-d test measuring survival, growth, and fecundity of Americamysis bahia formerly Mysidopsis bahia) was developed for estimating the chronic toxicity of effluents and associated receiving waters for National Pollutant Discharge Elimination System permits. Currently, this test...

ENANTIOSELECTIVE CHRONIC TOXICITY OF FIPRONIL TO CERIODAPHNIA DUBIA

EPA Science Inventory

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

Elucidating mechanisms of toxic action of dissolved organic chemicals in oil sands process-affected water (OSPW).

PubMed

Morandi, Garrett D; Wiseman, Steve B; Guan, Miao; Zhang, Xiaowei W; Martin, Jonathan W; Giesy, John P

2017-11-01

Oil sands process-affected water (OSPW) is generated during extraction of bitumen in the surface-mining oil sands industry in Alberta, Canada, and is acutely and chronically toxic to aquatic organisms. It is known that dissolved organic compounds in OSPW are responsible for most toxic effects, but knowledge of the specific mechanism(s) of toxicity, is limited. Using bioassay-based effects-directed analysis, the dissolved organic fraction of OSPW has previously been fractionated, ultimately producing refined samples of dissolved organic chemicals in OSPW, each with distinct chemical profiles. Using the Escherichia coli K-12 strain MG1655 gene reporter live cell array, the present study investigated relationships between toxic potencies of each fraction, expression of genes and characterization of chemicals in each of five acutely toxic and one non-toxic extract of OSPW derived by use of effects-directed analysis. Effects on expressions of genes related to response to oxidative stress, protein stress and DNA damage were indicative of exposure to acutely toxic extracts of OSPW. Additionally, six genes were uniquely responsive to acutely toxic extracts of OSPW. Evidence presented supports a role for sulphur- and nitrogen-containing chemical classes in the toxicity of extracts of OSPW. Copyright © 2017 Elsevier Ltd. All rights reserved.

An index of effluent aquatic toxicity designed by partial least squares regression, using acute and chronic tests and expert judgements.

PubMed

Vindimian, Éric; Garric, Jeanne; Flammarion, Patrick; Thybaud, Éric; Babut, Marc

1999-10-01

The evaluation of the ecotoxicity of effluents requires a battery of biological tests on several species. In order to derive a summary parameter from such a battery, a single endpoint was calculated for all the tests: the EC10, obtained by nonlinear regression, with bootstrap evaluation of the confidence intervals. Principal component analysis was used to characterize and visualize the correlation between the tests. The table of the toxicity of the effluents was then submitted to a panel of experts, who classified the effluents according to the test results. Partial least squares (PLS) regression was used to fit the average value of the experts' judgements to the toxicity data, using a simple equation. Furthermore, PLS regression on partial data sets and other considerations resulted in an optimum battery, with two chronic tests and one acute test. The index is intended to be used for the classification of effluents based on their toxicity to aquatic species. Copyright © 1999 SETAC.

An index of effluent aquatic toxicity designed by partial least squares regression, using acute and chronic tests and expert judgments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vindimian, E.; Garric, J.; Flammarion, P.

1999-10-01

The evaluation of the ecotoxicity of effluents requires a battery of biological tests on several species. In order to derive a summary parameter from such a battery, a single endpoint was calculated for all the tests: the EC10, obtained by nonlinear regression, with bootstrap evaluation of the confidence intervals. Principal component analysis was used to characterize and visualize the correlation between the tests. The table of the toxicity of the effluents was then submitted to a panel of experts, who classified the effluents according to the test results. Partial least squares (PLS) regression was used to fit the average valuemore » of the experts' judgments to the toxicity data, using a simple equation. Furthermore, PLS regression on partial data sets and other considerations resulted in an optimum battery, with two chronic tests and one acute test. The index is intended to be used for the classification of effluents based on their toxicity to aquatic species.« less

Assessing changes in the toxicity of effluents from intensive marine fish farms over time by using a battery of bioassays.

PubMed

Carballeira, Carlos; Cebro, Alesandra; Villares, Rubén; Carballeira, Alejo

2018-05-01

Although intensive marine fish farming is often assumed to be eco-friendly, the associated activity can lead to chronic exposure of marine organisms to potentially toxic discharges. Moreover, despite the increasing popularity of integrated multi-trophic aquaculture (IMTA), studies of the effects of fish farm effluents are almost non-existent. In the present study, the changes in the toxic potential of effluents from five land-based marine fish farms in NW Spain subjected for different lengths of time to a biodegradation procedure (for 0, 48, 120, and 240 h) were assessed in a battery of bioassays including organisms from different trophic levels (Vibrio fischeri, Isochrysis galbana, and Paracentrotus lividus). The results of the bioassays at the different times were then considered together with farm water flow in the Potential Ecotoxic Effects Probe (PEEP) index. Despite the high volumes of effluents discharged, the generally low toxicity of the effluents hinders assessment of potentially toxic effects. However, dose-response curves and statistical analysis demonstrated the existence of toxic effects during the first five days of the biodegradation procedure, especially immediately after sampling. The proposed modification of the PEEP index better reflects the changes in toxicity over time. Graphical abstract ᅟ.

Elevated blood lead and cadmium levels associated with chronic infections among non-smokers in a cross-sectional analysis of NHANES data

EPA Science Inventory

BACKGROUND: Experimental animal studies, in vitro experiments, and clinical assessments have shown that metal toxicity can impair immune responses. We analyzed data from a United States representative National Health and Nutrition Examination Survey (NHANES) to explore associatio...

USING ROTIFER POPULATION DEMOGRAPHIC PARAMETERS TO ASSESS IMPACTS OF THE DEGRADATION PRODUCTS FROM TRINITROTOLUENE PHYTOREMEDIATION

EPA Science Inventory

The objective of this study was to evaluate the aquatic chronic lethal and sublethal toxicity effects from the phytoremediation of water contaminated with 2,4,6-trinitrotoluene (2,4,6-TNT) by the wetland plant species Myriophyllum aquaticum (parrot feather). Rotifers (Brachionus...

LONG-TERM EFFECTS OF ADVERSE ENVIRONMENTS DURING DEVELOPMENT: EFFECTS ON ADULTHOOD IN RATS EXPOSED TO TOXICANTS OR UNDERNUTRITION IN UTERO.

EPA Science Inventory

Studies have shown correlations between in utero and early life environments and diseases later in life, including hypertension, coronary heart disease, diabetes, obesity, schizophrenia, early onset chronic renal failure, cancer and compromised repro-duction. Current development...

MULTIMEDIA CHEMICAL ANALYSIS PLAN FOR CHILDREN'S AGGREGATE EXPOSURE FIELD STUDIES IN NORTH CAROLINA AND OHIO

EPA Science Inventory

The samples collected in the CTEPP North Carolina and Ohio field campaigns were analyzed for a suite of organic chemicals in various compound classes, chosen because of their possible carcinogenicity, acute or chronic toxicity, or potential for endocrine system disruption. The...

Pesticide exposure in children.

PubMed

Roberts, James R; Karr, Catherine J

2012-12-01

Pesticides are a collective term for a wide array of chemicals intended to kill unwanted insects, plants, molds, and rodents. Food, water, and treatment in the home, yard, and school are all potential sources of children's exposure. Exposures to pesticides may be overt or subacute, and effects range from acute to chronic toxicity. In 2008, pesticides were the ninth most common substance reported to poison control centers, and approximately 45% of all reports of pesticide poisoning were for children. Organophosphate and carbamate poisoning are perhaps the most widely known acute poisoning syndromes, can be diagnosed by depressed red blood cell cholinesterase levels, and have available antidotal therapy. However, numerous other pesticides that may cause acute toxicity, such as pyrethroid and neonicotinoid insecticides, herbicides, fungicides, and rodenticides, also have specific toxic effects; recognition of these effects may help identify acute exposures. Evidence is increasingly emerging about chronic health implications from both acute and chronic exposure. A growing body of epidemiological evidence demonstrates associations between parental use of pesticides, particularly insecticides, with acute lymphocytic leukemia and brain tumors. Prenatal, household, and occupational exposures (maternal and paternal) appear to be the largest risks. Prospective cohort studies link early-life exposure to organophosphates and organochlorine pesticides (primarily DDT) with adverse effects on neurodevelopment and behavior. Among the findings associated with increased pesticide levels are poorer mental development by using the Bayley index and increased scores on measures assessing pervasive developmental disorder, inattention, and attention-deficit/hyperactivity disorder. Related animal toxicology studies provide supportive biological plausibility for these findings. Additional data suggest that there may also be an association between parental pesticide use and adverse birth outcomes including physical birth defects, low birth weight, and fetal death, although the data are less robust than for cancer and neurodevelopmental effects. Children's exposures to pesticides should be limited as much as possible.

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

PubMed Central

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-01-01

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects.

PubMed

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-12-02

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

Two-Year Chronic Toxicity Study in Rats

DTIC Science & Technology

1976-08-27

LD C. 0- N. 00 C! cc ’. 0 C- Nl CD c n * co CD C;’. Ln Lo Ln fn ’. 1cC c; 0 N N cm0 w jL- v; c I’ioON0 17 r’-O COOr c.,J C’o co ŕ " C’, C9f COW ...Focal granulomatosis 1% Chronic abscesses 1% Integument Pyogenic granuloma 1% Abscess 1% Mammary Gland Cystic hyperplasia 1% Chronic mastiti I... mastitis 1 73 I Uterus *Neopl asms 1 73 Hydrometra 1 73 Multiple Distribution oF ter-tis 1 73 S~Integument Neoplasm 2 73 -4No Oran Speci :ied Neoplasm 6

Treating chronic arsenic toxicity with high selenium lentil diets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sah, Shweta; Vandenberg, Albert; Smits, Judit, E-mail: judit.smits@ucalgary.ca

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 comparemore » 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 response.« less

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. © 2015 SETAC.

[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.

Prospective Environmental Risk Assessment for Sediment-Bound Organic Chemicals: A Proposal for Tiered Effect Assessment.

PubMed

Diepens, Noël J; Koelmans, Albert A; Baveco, Hans; van den Brink, Paul J; van den Heuvel-Greve, Martine J; Brock, Theo C M

A broadly accepted framework for prospective environmental risk assessment (ERA) of sediment-bound organic chemicals is currently lacking. Such a framework requires clear protection goals, evidence-based concepts that link exposure to effects and a transparent tiered-effect assessment. In this paper, we provide a tiered prospective sediment ERA procedure for organic chemicals in sediment, with a focus on the applicable European regulations and the underlying data requirements. Using the ecosystem services concept, we derived specific protection goals for ecosystem service providing units: microorganisms, benthic algae, sediment-rooted macrophytes, benthic invertebrates and benthic vertebrates. Triggers for sediment toxicity testing are discussed.We recommend a tiered approach (Tier 0 through Tier 3). Tier-0 is a cost-effective screening based on chronic water-exposure toxicity data for pelagic species and equilibrium partitioning. Tier-1 is based on spiked sediment laboratory toxicity tests with standard benthic test species and standardised test methods. If comparable chronic toxicity data for both standard and additional benthic test species are available, the Species Sensitivity Distribution (SSD) approach is a more viable Tier-2 option than the geometric mean approach. This paper includes criteria for accepting results of sediment-spiked single species toxicity tests in prospective ERA, and for the application of the SSD approach. We propose micro/mesocosm experiments with spiked sediment, to study colonisation success by benthic organisms, as a Tier-3 option. Ecological effect models can be used to supplement the experimental tiers. A strategy for unifying information from various tiers by experimental work and exposure-and effect modelling is provided.

Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure.

PubMed

Sinha, Amitasha; Patel, Yuval A; Cruise, Michael; Matsukuma, Karen; Zaheer, Atif; Afghani, Elham; Yadav, Dhiraj; Makary, Martin A; Hirose, Kenzo; Andersen, Dana K; Singh, Vikesh K

2016-04-01

Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p < 0.01). However, only a toxic etiology was an independent predictor of post-operative pain relief (OR 5.7, 95% CI 1.3, 24.5, p = 0.02). Only a toxic etiology, and not imaging or histopathologic findings, independently predicts post-operative pain relief in CP patients undergoing the Whipple or Frey procedure.

Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem Bark Extract in Rats

PubMed Central

Okonkwo, T. J. N.; Okorie, O.; Okonta, J. M.; Okonkwo, C. J.

2010-01-01

The extracts of Anacardium occidentale have been used in the management of different cardiovascular disorders in Nigeria. These have necessitated the assessment of the toxicity of this plant extract in sub-chronic administration. The inner stem bark of Anacardium occidentale was extracted with 80 % methanol and quantitatively analysed for antinutrients and some heavy metals. The phytochemical compositions and acute toxicity of the extract were determined also. Toxicity profiles of the extract on some liver function parameters were evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87 g/kg. The phytochemical screening of extract revealed the presence of high amount of tannins, moderate saponins and trace of free reducing sugars. The antinutrient levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 % (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had LD50of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract significantly increased the serum levels of alanine aminotransaminase and aspartate aminotransaminase, which are indicative of liver damage. The serum levels of alkaline phosphatase and total protein of the treated animals were not significantly increased. The effects of sub-chronically administered extract on hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and total protein levels in treated animals were not significant (p< 0.05). Thus, sub-chronic administrations of Anacardium occidentale inner stem bark extract did not significantly (p< 0.05) depress the function of hepatocytes in Wistar rats. PMID:21188045

Glossary of Aquatic Ecological Terms,

DTIC Science & Technology

1972-02-01

changes. ACUTE TOXICITY Any toxic effect that is produced within a short period of time, usually 24-96 hours. Although the effect most frequently...considered is mortality, the end result of acute toxicity is not necessarily death. Any harmful biolopical effect may be the result. (See Chronic...manufacture of organic compounds within an organism. (See Metabolism ) 4. *1 -ib- ~:2~ ’ A- 3 I ANADROHOUS Pertaining to fishes that speid most of their

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...

COMPARATIVE TOXICITY OF FLUORANTHENE TO FRESHWATER AND SALTWATER SPECIES UNDER FLUORESCENT AND ULTRAVIOLET LIGHT

EPA Science Inventory

The acute and chronic toxicity of fluoranthene was determined for a diverse group of freshwater and saltwater species under both standard laboratory fluorescent light and ultraviolet (UV) light test conditions. Acute tests with 21 species demonstrated that fluoranthene was not le...

40 CFR 799.1053 - Trichlorobenzenes.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-trichlorobenzenes. Testing shall be conducted with mysid shrimp (Mysidopis bahia) to develop data on the acute... invertebrate (mysid shrimp, Mysidopis bahia) acute toxicity testing for 1,2,3- and 1,2,4-trichlorobenzenes... after the effective date of the final Phase II rule. (5) Mysid shrimp chronic toxicity testing—(i...

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

EPA Pesticide Factsheets

as part of EPA's Hydraulic Fracturing Drinking Water Assessment, EPA is summarizing existing toxicity data for chemicals reported to be used in hydraulic fracturing fluids and/or found in flowback or produced waters from hydraulically fractured wells

Biological and chemical characterization of metal bioavailability in sediments from Lake Roosevelt, Columbia River, Washington, USA

USGS Publications Warehouse

Besser, J.M.; Brumbaugh, W.G.; Ivey, C.D.; Ingersoll, C.G.; Moran, P.W.

2008-01-01

We studied the bioavailability and toxicity of copper, zinc, arsenic, cadmium, and lead in sediments from Lake Roosevelt (LR), a reservoir on the Columbia River in Washington, USA that receives inputs of metals from an upstream smelter facility. We characterized chronic sediment toxicity, metal bioaccumulation, and metal concentrations in sediment and pore water from eight study sites: one site upstream in the Columbia River, six sites in the reservoir, and a reference site in an uncontaminated tributary. Total recoverable metal concentrations in LR sediments generally decreased from upstream to downstream in the study area, but sediments from two sites in the reservoir had metal concentrations much lower than adjacent reservoir sites and similar to the reference site, apparently due to erosion of uncontaminated bank soils. Concentrations of acid-volatile sulfide in LR sediments were too low to provide strong controls on metal bioavailability, and selective sediment extractions indicated that metals in most LR sediments were primarily associated with iron and manganese oxides. Oligochaetes (Lumbriculus variegatus) accumulated greatest concentrations of copper from the river sediment, and greatest concentrations of arsenic, cadmium, and lead from reservoir sediments. Chronic toxic effects on amphipods (Hyalella azteca; reduced survival) and midge larvae (Chironomus dilutus; reduced growth) in whole-sediment exposures were generally consistent with predictions of metal toxicity based on empirical and equilibrium partitioning-based sediment quality guidelines. Elevated metal concentrations in pore waters of some LR sediments suggested that metals released from iron and manganese oxides under anoxic conditions contributed to metal bioaccumulation and toxicity. Results of both chemical and biological assays indicate that metals in sediments from both riverine and reservoir habitats of Lake Roosevelt are available to benthic invertebrates. These findings will be used as part of an ongoing ecological risk assessment to determine remedial actions for contaminated sediments in Lake Roosevelt. ?? 2007 Springer Science+Business Media, LLC.

[Preclinical studies of an adsorbed diphtheria-tetanus-pertussis vaccine (ADTP-vaccine) with acellular pertussis component].

PubMed

Zaĭtsev, E M; Britsina, M V; Bazhanova, I G; Mertsalova, N U; Ozeretskovskaia, M N; Ermolova, E V; Plekhanova, N G; Mikhaĭlova, N A; Kolyshkin, V A; Zverev, V V

2013-01-01

Evaluate standardness of antigenic composition of pertussis component, completeness of sorption of pertussis, diphtheria and tetanus components, specific activity and safety of experimental series ofADTP-vaccine with acellular pertussis component (ADTaP-vaccine). The content of separate antigens (pertussis toxin, filamentous hemagglutinin and agglutinogens 1, 2, 3) in samples of acellular pertussis component of ADTaP-vaccine and completeness of sorption of pertussis component of ADTaP-vaccine were evaluated by using enzyme immunoassay. Completeness of sorption of diphtheria and tetanus components were determined in flocculation reaction and antitoxin-binding reactions, respectively. Protective activity ofADTaP-vaccine was studied in model ofmeningoencephalitis development in mice infected with Bordetella pertussis (strain 18323) neurotropic virulent culture, protective activity oftetanus component - by survival of mice after administration of tetanus toxin, protective activity of diphtheria component - by survival of guinea pigs after administration of diphtheria toxin. Safety of preparations was evaluated in tests of acute and chronic toxicity with carrying out pathomorphologic studies including immature animals. All the studied experimental series ofADTaP-vaccine were standard by content of separate antigens of pertussis microbe. All the ADTaP-vaccine components were completely sorbed on aluminium hydroxide gel. By protective activity ADTaP preparations satisfied the WHO requirements. The preparations were non-toxic in acute and chronic toxicity and did not induce pathomorphologic changes including immature animals. Experimental samples of ADTaP-vaccine by specific activity and safety satisfied WHO requirements.

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

PubMed

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

2010-09-01

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

Chronic toxicity of copper on embryo development in Chinese toad, Bufo gargarizans.

PubMed

Xia, Kun; Zhao, Hongfeng; Wu, Minyao; Wang, Hongyuan

2012-06-01

This study examined the effects of copper exposure on embryonic development of Chinese toad, Bufo gargarizans. Firstly, the LC(50) values from 24 to 96 h of exposure were 3.61×10(-6) M, by means of a 4 d toxicity test with B. gargarizans embryos. Secondly, Chinese toad embryos were exposed to 10(-9)-10(-6) M copper from mid gastrula stage to operculum completion stage. Measurements included mortality, tadpole weight, tadpole total length, growth retardation, duration of different embryo stages and malformation. Embryonic survival was not affected by copper. Relative to control tadpoles, significantly decreased weight and total length were found at 10(-9)-10(-6) M reduced percentage of the embryos in right operculum stage after 10 d exposure to copper and reduced percentage of embryos in operculum completion stage after 12 d exposure to copper were also observed. Moreover, the duration of embryonic development increased at neural, circulation and operculum development stage in copper-treated groups. For the scanning microscope and histological observation, the abnormalities were malformation of wavy dorsal fin, flexural tail, curvature body axis, yolk sac oedema and reduced pigmentation in the yolk sac. Histopathological changes in olfactory, retinal epithelium and skin were also observed. DNA strand breaks exposed to the copper were analyzed by DNA ladder. In conclusion, copper induced toxic effects on B. gargarizans embryos. The present study indicated chronic toxicity tests may provide more accurate way in formulating the "safe levels" of heavy metals to amphibian. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheshchevik, V.T.; Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno; Lapshina, E.A.

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, pmore » < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl{sub 4} intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 beenmore » 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.« less

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Liver Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1, but not with degree of induction in hepatocellular proliferation. In sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver protein levels of Cyp2e1, Adh and Aldh2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. PMID:25424544

Ecotoxicological assessment of biosolids by microcosms.

PubMed

Groth, Vitor Avelar; Carvalho-Pereira, Ticiana; da Silva, Eduardo Mendes; Niemeyer, Júlia Carina

2016-10-01

Biosolids have been applied as soil amendments to improve and maintain the soil fertility and faster plant growth. In spite of its beneficial use, the potential risks of land disposal should be analyzed, considering potential ecological receptors in soil and water. This work describes the use of an early warning laboratory microcosm system to evaluate the integrated ecotoxicological potential of two biosolids: BIO-1 and BIO-2 (18 and 28 months after landfarming, respectively), from an effluent treatment station in a petrochemical and industrial district. The endpoints related to habitat function were: a) germination, growth and biomass of Phaseolus vulgaris; b) survival, biomass and number of cocoons of Eisenia andrei (Oligochaeta) and; c) reproduction of Folsomia candida (Collembola). The retention function was evaluated by testing the leachates using the tropical cladoceran Latonopsis australis (Cladocera) in a 48-h acute toxicity test, and growth of the aquatic plant Lemna minor in a 7-d chronic test. Tropical artificial soil (TAS) and a natural soil (NS) from the region were used as control soils. Results showed no chronic toxicity of BIO-1 and BIO-2 to the soil organisms tested, but acute toxicity of BIO-1 in the leachate for 50% of L. australis, and chronic toxicity of both biosolid leachates to L. minor (inhibition of growth rate), indicating potential risks to aquatic ecosystems. The results confirmed the ability of this microcosm system as a rapid tool to assess biosolid toxicity over time and its potential for hazardous waste characterization in environmental risk assessment, in a screening phase. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

In vivo investigation on the chronic hepatotoxicity induced by sertraline.

PubMed

Almansour, Mansour I; Jarrar, Yazun B; Jarrar, Bashir M

2018-05-30

Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100 g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8 mg/kg) for 9 weeks. The animals were subjected to morphometric, hepatohistological, histochemical and quantitative real-time polymerase chain reaction analyses. Sertraline chronic exposure induced morphometric changes and provoked histological and histochemical alterations including: hepatocytes hydropic degeneration, necrosis, nuclear alteration, sinusoidal dilation, bile duct hyperplasia, inflammatory cells infiltration, portal vessel congestion, Kupffer cells hyperplasia, portal fibrosis and glycogen depletion. In addition, the gene expression of drug and arachidonic acid metabolizing enzymes were reduced significantly (p value <0.05). The most affected genes were cyp4a12, ephx2, cyp2d9 and cyp1a2, demonstrating 5 folds or more down-regulation. These findings suggest that chronic sertraline treatment induced toxic histological alterations in the hepatic tissues and reduced the gene expression of drug metabolizing enzymes. Patients on chronic sertraline treatment may be on risk of hepatotoxicity with reduced capacity to metabolize drugs and fatty acids. Copyright © 2018 Elsevier B.V. All rights reserved.

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 ...

Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients

ClinicalTrials.gov

2018-03-30

Acute Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Small Lymphocytic Lymphoma

Sediment toxicity testing with the amphipod Ampelisca abdita in Calcasieu Estuary, Louisiana

USGS Publications Warehouse

Redmond, M.S.; Crocker, P.A.; McKenna, K.M.; Petrocelli, E.A.; Scott, K.J.; Demas, C.R.

1996-01-01

Discharges from chemical and petrochemical manufacturing facilities have contaminated portions of Louisiana's Calcasieu River estuary with a variety of organic and inorganic contaminants. As part of a special study, sediment toxicity testing was conducted to assess potential impact to the benthic community. Ten-day flow-through sediment toxicity tests with the amphipod Ampelisca abdita revealed significant toxicity at 68% (26 of 38) of the stations tested. A. abdita mortality was highest in the effluent-dominated bayous, which are tributaries to the Calcasieu River. Mortality was correlated with total heavy metal and total organic compound concentrations in the sediments. Ancillary experiments showed that sediment interstitial water salinity as low as 2.5 o/o-o did not significantly affect A. abdita's, response in the flow-through system; sediment storage for 7 weeks at 4??C did not significantly affect toxicity. Sediment toxicity to A. abdita was more prevalent than receiving water toxicity using three short-term chronic bioassays. Results suggest that toxicity testing using this amphipod is a valuable tool when assessing sediments containing complex contaminant mixtures and for assessing effects of pollutant loading over time. In conjunction with chemical analyses, the testing indicated that the effluent-dominated, brackish bayous (Bayou d'Inde and Bayou Verdine) were the portions of the estuary most impacted by toxicity.

Ecotoxicity hazard assessment of styrene.

PubMed

Cushman, J R; Rausina, G A; Cruzan, G; Gilbert, J; Williams, E; Harrass, M C; Sousa, J V; Putt, A E; Garvey, N A; St Laurent, J P; Hoberg, J R; Machado, M W

1997-07-01

The ecotoxicity of styrene was evaluated in acute toxicity studies of fathead minnows (Pimephales promelas), daphnids (Daphnia magna), amphipods (Hyalella azteca), and freshwater green algae (Selenastrum capricornutum), and a subacute toxicity study of earthworms (Eisenia fostida). Stable exposure levels were maintained in the studies with fathead minnows, daphnids, and amphipods using sealed, flowthrough, serial dilution systems and test vessels. The algae were evaluated in a sealed, static system. The earthworms were exposed in artificial soil which was renewed after 7 days. Styrene concentrations in water and soil were analyzed by gas chromatography with flame ionization detection following extraction into hexane. Test results are based on measured concentrations. Styrene was moderately toxic to fathead minnows, daphnids, and amphipods: fathead minnow: LC50 (96 hr), 10 mg/liter, and NOEC, 4.0 mg/liter; daphnids: EC50 (48 hr), 4.7 mg/liter, and NOEC, 1.9 mg/liter; amphipods: LC50 (96 hr), 9.5 mg/liter, and NOEC, 4.1 mg/liter. Styrene was highly toxic to green algae: EC50 (96 hr), 0.72 mg/liter, and NOEC, 0.063 mg/liter; these effects were found to be algistatic rather than algicidal. Styrene was slightly toxic to earthworms: LC50 (14 days), 120 mg/kg, and NOEC, 44 mg/kg. There was no indication of a concern for chronic toxicity based on these studies. Styrene's potential impact on aquatic and soil environments is significantly mitigated by its volatility and biodegradability.

Validation of the AOP network “Thyroperoxidase and/or deiodinase inhibition leading to impaired swim bladder inflation”

EPA Science Inventory

Industrial chemicals released in the aquatic environment can pose risks for both environmental and human health. Fish are widely used sentinels for evaluating aquatic toxicity to vertebrates in order to set environmental quality standards, However, chronic toxicity testing with f...

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...

TISSUE DISTRIBUTION OF ARSENIC SPECIES IN MICE CHRONICALLY EXPOSED TO METHYLARSONOUS ACID

EPA Science Inventory

The metabolism of inorganic arsenic (iAs) in humans yields toxic and carcinogenic methyl-As (MAs) and dimethyl-As (DMAs) intermediates. Methylarsonous acid (MAsIII) is the most acutely toxic species of characterized iAs metabolites. Here, we examined the concentrations of As spec...

Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels

EPA Science Inventory

Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...

BIOMARKERS OF PM EXPOSURE TO COMBUSTION SOURCE EMISSIONS & ORGANIC (TOXIC) COMPONENTS

EPA Science Inventory

Fine particles (PM2.5) and associated semivolatile organic compounds (SVOC) contain a very complex mixture of both organic and inorganic chemicals that may contribute to toxicity of the particles. The health effects of PM2.5 exposures in humans result from both acute and chronic...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

... Research on Cancer's (IARC) Group 1, or the American National Standards Institute's (ANSI) Category 1. A... or quantitative limitations with respect to experimental procedures (e.g., doses, exposure, follow-up... absorption of the toxic substance, and (D) Dose. (3) Assessment of Risk. This section on quantitative risk...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... Research on Cancer's (IARC) Group 1, or the American National Standards Institute's (ANSI) Category 1. A... or quantitative limitations with respect to experimental procedures (e.g., doses, exposure, follow-up... absorption of the toxic substance, and (D) Dose. (3) Assessment of Risk. This section on quantitative risk...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... Research on Cancer's (IARC) Group 1, or the American National Standards Institute's (ANSI) Category 1. A... or quantitative limitations with respect to experimental procedures (e.g., doses, exposure, follow-up... absorption of the toxic substance, and (D) Dose. (3) Assessment of Risk. This section on quantitative risk...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

... Research on Cancer's (IARC) Group 1, or the American National Standards Institute's (ANSI) Category 1. A... or quantitative limitations with respect to experimental procedures (e.g., doses, exposure, follow-up... absorption of the toxic substance, and (D) Dose. (3) Assessment of Risk. This section on quantitative risk...

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

Code of Federal Regulations, 2014 CFR

2014-01-01

... Research on Cancer's (IARC) Group 1, or the American National Standards Institute's (ANSI) Category 1. A... or quantitative limitations with respect to experimental procedures (e.g., doses, exposure, follow-up... absorption of the toxic substance, and (D) Dose. (3) Assessment of Risk. This section on quantitative risk...

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...

Lithium Poisoning.

PubMed

Baird-Gunning, Jonathan; Lea-Henry, Tom; Hoegberg, Lotte C G; Gosselin, Sophie; Roberts, Darren M

2017-05-01

Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

PubMed Central

2016-01-01

Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported. PMID:27896275

Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Storage Time on Sediment Toxicity

DTIC Science & Technology

1994-04-01

Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Storage Time on Sediment...Dredging Miscellaneous Paper D-94-2 Operations Program April 1994 Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes...tWatelrway EnD A2AIM a MI F~YRA • rI~WATIMA. •7 WATCH Moore, David W. Chronic sublethal effects of San Francisco Bay sediments on Nerels (Neanthes

Use of the Romanian product Silimarina in the treatment of chronic liver diseases.

PubMed

Tănăsescu, C; Petrea, S; Băldescu, R; Macarie, E; Chiriloiu, C; Purice, S

1988-01-01

The Romanian product Silimarina (synonym Legalon) was administered in a randomized double-blind trial, to a group of 180 patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) and hepatic cirrhosis (HC). The trial lasted for 40 days. The results showed favourable effects similar with those obtained with other preparations produced by foreign drug industries. The Romanian product proved to have no toxic effect. The authors discuss the present possibilities of estimating the evolution of chronic liver disease.

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid).

PubMed

Fairchild, James F; Allert, Ann; Sappington, Linda S; Nelson, Karen J; Valle, Janet

2008-03-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration:time data matrix.

Using accelerated life testing procedures to compare the relative sensitivity of rainbow trout and the federally listed threatened bull trout to three commonly used rangeland herbicides (picloram, 2,4-D, and clopyralid)

USGS Publications Warehouse

Fairchild, J.F.; Allert, A.; Sappington, L.S.; Nelson, K.J.; Valle, J.

2008-01-01

We conducted 96-h static acute toxicity studies to evaluate the relative sensitivity of juveniles of the threatened bull trout (Salvelinus confluentus) and the standard cold-water surrogate rainbow trout (Onchorhyncus mykiss) to three rangeland herbicides commonly used for controlling invasive weeds in the northwestern United States. Relative species sensitivity was compared using three procedures: standard acute toxicity testing, fractional estimates of lethal concentrations, and accelerated life testing chronic estimation procedures. The acutely lethal concentrations (ALC) resulting in 50% mortality at 96 h (96-h ALC50s) were determined using linear regression and indicated that the three herbicides were toxic in the order of picloram acid > 2,4-D acid > clopyralid acid. The 96-h ALC50 values for rainbow trout were as follows: picloram, 41 mg/L; 2.4-D, 707 mg/L; and clopyralid, 700 mg/L. The 96-h ALC50 values for bull trout were as follows: picloram, 24 mg/L; 2.4-D, 398 mg/L; and clopyralid, 802 mg/L. Fractional estimates of safe concentrations, based on 5% of the 96-h ALC50, were conservative (overestimated toxicity) of regression-derived 96-h ALC5 values by an order of magnitude. Accelerated life testing procedures were used to estimate chronic lethal concentrations (CLC) resulting in 1% mortality at 30 d (30-d CLC1) for the three herbicides: picloram (1 mg/L rainbow trout, 5 mg/L bull trout), 2,4-D (56 mg/L rainbow trout, 84 mg/L bull trout), and clopyralid (477 mg/L rainbow trout; 552 mg/L bull trout). Collectively, the results indicated that the standard surrogate rainbow trout is similar in sensitivity to bull trout. Accelerated life testing procedures provided cost-effective, statistically defensible methods for estimating safe chronic concentrations (30-d CLC1s) of herbicides from acute toxicity data because they use statistical models based on the entire mortality:concentration: time data matrix. ?? 2008 SETAC.

Effects of Magnesium on the Phosphate Toxicity in Chronic Kidney Disease: Time for Intervention Studies.

PubMed

Sakaguchi, Yusuke; Hamano, Takayuki; Isaka, Yoshitaka

2017-02-06

Magnesium, an essential mineral for human health, plays a pivotal role in the cardiovascular system. Epidemiological studies in the general population have found an association between lower dietary magnesium intake and an elevated risk of cardiovascular events. In addition, magnesium supplementation was shown to improve blood pressure control, insulin sensitivity, and endothelial function. The relationship between magnesium and cardiovascular prognosis among patients with chronic kidney disease (CKD) has been increasingly investigated as it is becoming evident that magnesium can inhibit vascular calcification, a prominent risk of cardiovascular events, which commonly occurs in CKD patients. Cohort studies in patients receiving dialysis have shown a lower serum magnesium level as a significant risk for cardiovascular mortality. Interestingly, the cardiovascular mortality risk associated with hyperphosphatemia is alleviated among those with high serum magnesium levels, consistent with in vitro evidence that magnesium inhibits high-phosphate induced calcification of vascular smooth muscle cells. Furthermore, a harmful effect of high phosphate on the progression of CKD is also attenuated among those with high serum magnesium levels. The potential usefulness of magnesium as a remedy for phosphate toxicity should be further explored by future intervention studies.

Effects of Magnesium on the Phosphate Toxicity in Chronic Kidney Disease: Time for Intervention Studies

PubMed Central

Sakaguchi, Yusuke; Hamano, Takayuki; Isaka, Yoshitaka

2017-01-01

Magnesium, an essential mineral for human health, plays a pivotal role in the cardiovascular system. Epidemiological studies in the general population have found an association between lower dietary magnesium intake and an elevated risk of cardiovascular events. In addition, magnesium supplementation was shown to improve blood pressure control, insulin sensitivity, and endothelial function. The relationship between magnesium and cardiovascular prognosis among patients with chronic kidney disease (CKD) has been increasingly investigated as it is becoming evident that magnesium can inhibit vascular calcification, a prominent risk of cardiovascular events, which commonly occurs in CKD patients. Cohort studies in patients receiving dialysis have shown a lower serum magnesium level as a significant risk for cardiovascular mortality. Interestingly, the cardiovascular mortality risk associated with hyperphosphatemia is alleviated among those with high serum magnesium levels, consistent with in vitro evidence that magnesium inhibits high-phosphate induced calcification of vascular smooth muscle cells. Furthermore, a harmful effect of high phosphate on the progression of CKD is also attenuated among those with high serum magnesium levels. The potential usefulness of magnesium as a remedy for phosphate toxicity should be further explored by future intervention studies. PMID:28178182

Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

PubMed

Noronha, M; Dreiling, D A; Bordalo, O

1983-11-01

A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

EPA Science Inventory

The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

Pre-clinical efficacy assessment of Malva sylvestris on chronic skin inflammation.

PubMed

Prudente, Arthur S; Sponchiado, Graziela; Mendes, Daniel A G B; Soley, Bruna S; Cabrini, Daniela A; Otuki, Michel F

2017-09-01

In the search for improved quality of life, the treatment of skin diseases like psoriasis (hyperproliferative disease) is valid, since it causes huge social discomfort to the patient. In this context, earlier studies showed that Malva sylvestris L. has anti-inflammatory activity demonstrated by acute animal models of skin inflammation, becoming a promising target for further studies. The present investigation aimed to verify the effect of hydroalcoholic extract of M. sylvestris (HEMS) on the chronic inflammatory and hyperproliferative response caused by multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on mouse ears. Topical application of HEMS reduced oedema, leukocyte migration (mono- and polymorphonuclear cells) and keratinocyte hyperproliferation, confirmed by histology and proliferating cell nuclear antigen (PCNA) immunostaining. It was found that the anti-inflammatory effects of the extract did not involve the glucocorticoid system, and its incubation with HaCaT keratinocytes caused low toxicity and reduced cell proliferation by apoptosis. Thus, HEMS proved to be effective as an anti-psoriatic therapy, with the ability to prevent keratinocyte hyperproliferation and with low toxicity by topical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.

PubMed

Wiernik, P H; Gordon, L I; Oken, M M; Harris, J E; O'Connell, M J

1999-10-01

Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. We, therefore, tested this agent for activity against chronic lymphocytic leukemia (CLL) in this phase II study. Mitoguazone, 500 mg/M2 was given intravenously weekly to 13 patients with relapsed or refractory, previously treated Rai stages 2-4 CLL. There were no complete or partial responses as judged by standard criteria. Toxicity was acceptable. Mitoguazone in the dose and schedule employed in this study has no significant activity as a single agent in patients with relapsed or refractory CLL.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

PubMed

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M; Wilks, Martin F; Spandidos, Demetrios A; Fenga, Concettina

2016-10-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review)

PubMed Central

Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M.; Wilks, Martin F.; Spandidos, Demetrios A.; Fenga, Concettina

2016-01-01

Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases. PMID:27600395

Adaptation to chronic MG132 reduces oxidative toxicity by a CuZnSOD-dependent mechanism

PubMed Central

Leak, Rehana K.; Zigmond, Michael J.; Liou, Anthony K. F.

2010-01-01

To study whether and how cells adapt to chronic cellular stress, we exposed PC12 cells to the proteasome inhibitor MG132 (0.1 μM) for 2 weeks and longer. This treatment reduced chymotrypsin-like proteasome activity by 47% and was associated with protection against both 6-hydroxydopamine (6-OHDA, 100 μM) and higher dose MG132 (40 μM). Protection developed slowly over the course of the first 2 weeks of exposure and was chronic thereafter. There was no change in total glutathione levels after MG132. Buthionine sulfoximine (100 μM) reduced glutathione levels by 60%, but exacerbated 6-OHDA toxicity to the same extent in both MG132-treated and control cells and failed to reduce MG132-induced protection. Chronic MG132 resulted in elevated antioxidant proteins CuZn superoxide dismutase (SOD, +55%), MnSOD (+21%), and catalase (+15%), as well as chaperone heat shock protein 70 (+42%). Examination of SOD enzyme activity revealed higher levels of CuZnSOD (+40%), with no change in MnSOD. We further assessed the mechanism of protection by reducing CuZnSOD levels with two independent siRNA sequences, both of which successfully attenuated protection against 6-OHDA. Previous reports suggested that artificial overexpression of CuZnSOD in dopaminergic cells is protective. Our data complement such observations, revealing that dopaminergic cells are also able to use endogenous CuZnSOD in self-defensive adaptations to chronic stress, and that they can even do so in the face of extensive glutathione loss. PMID:18466318

Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

PubMed Central

Balali-Mood, M; Mousavi, SH; Balali-Mood, B

2008-01-01

The widespread use of sulphur mustard (SM) as an incapacitating chemical warfare agent in the past century has proved its long-lasting toxic effects. It may also be used as a chemical terrorist agent. Therefore, all health professionals should have sufficient knowledge and be prepared for any such chemical attack. SM exerts direct toxic effects on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, immunological, haematological, digestive, and reproductive systems. SM is an alkylating agent that affects DNA synthesis, and, thus, delayed complications have been seen since the First World War. Cases of malignancies in the target organs, particularly in haematopoietic, respiratory, and digestive systems, have been reported. Important delayed respiratory complications include chronic bronchitis, bronchiectasis, frequent bronchopneumonia, and pulmonary fibrosis, all of which tend to deteriorate with time. Severe dry skin, delayed keratitis, and reduction of natural killer cells with subsequent increased risk of infections and malignancies are also among the most distressing long-term consequences of SM intoxication. However, despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Immunological and neurological dysfunction, as well as the relationship between SM exposure and mutagenicity, carcinogenicity, and teratogenicity are important fields that require further studies, particularly on Iranian veterans with chronic health effects of SM poisoning. There is also a paucity of information on the medical management of acute and delayed toxic effects of SM poisoning—a subject that greatly challenges health care specialists. PMID:22460216

Selective Thinning of the Perifoveal Inner Retina as an Early Sign of Hydroxychloroquine Retinal Toxicity

PubMed Central

Pasadhika, Sirichai; Fishman, Gerald A; Choi, Dongseok; Shahidi, Mahnaz

2013-01-01

Purpose To evaluate macular thickness profiles using spectral-domain optical coherence tomography (SDOCT) and image segmentation in patients with chronic exposure to hydroxychloroquine. Methods This study included 8 patients with chronic exposure to hydroxychloroquine (Group 1) and 8 controls (Group 2). Group 1 patients had no clinically-evident retinal toxicity. All subjects underwent SDOCT imaging of the macula. An image segmentation technique was used to measure thickness of 6 retinal layers at 200 µm intervals. A mixed-effects model was used for multivariate analysis. Results By measuring total retinal thickness either at the central macular (2800 µm in diameter), the perifoveal region 1200-µm-width ring surrounding the central macula), or the overall macular area (5200 µm in diameter), there were no significant differences in the thickness between Groups 1 and 2. On an image segmentation analysis, selective thinning of the inner plexiform + ganglion cell layers (p=0.021) was observed only in the perifoveal area of the patients in Group 1 compared to that of Group 2 by using the mixed-effects model analysis. Conclusions Our results suggest that chronic exposure to hydroxychloroquine is associated with thinning of the perifoveal inner retinal layers, especially in the ganglion cell and inner plexiform layers, even in the absence of functional or structural clinical changes involving the photoreceptor or retinal pigment epithelial cell layers. This may be a contributing factor as the reason most patients who have early detectable signs of drug toxicity present with paracentral or pericentral scotomas. PMID:20395978

Mitochondrionopathy phenotype in doxorubicin-treated Wistar rats depends on treatment protocol and is cardiac-specific.

PubMed

Pereira, Gonçalo C; Pereira, Susana P; Pereira, Claudia V; Lumini, José A; Magalhães, José; Ascensão, António; Santos, Maria S; Moreno, António J; Oliveira, Paulo J

2012-01-01

Although doxorubicin (DOX) is a very effective antineoplastic agent, its clinical use is limited by a dose-dependent, persistent and cumulative cardiotoxicity, whose mechanism remains to be elucidated. Previous works in animal models have failed to use a multi-organ approach to demonstrate that DOX-associated toxicity is selective to the cardiac tissue. In this context, the present work aims to investigate in vivo DOX cardiac, hepatic and renal toxicity in the same animal model, with special relevance on alterations of mitochondrial bioenergetics. To this end, male Wistar rats were sub-chronically (7 wks, 2 mg/Kg) or acutely (20 mg/Kg) treated with DOX and sacrificed one week or 24 hours after the last injection, respectively. Alterations of mitochondrial bioenergetics showed treatment-dependent differences between tissues. No alterations were observed for cardiac mitochondria in the acute model but decreased ADP-stimulated respiration was detected in the sub-chronic treatment. In the acute treatment model, ADP-stimulated respiration was increased in liver and decreased in kidney mitochondria. Aconitase activity, a marker of oxidative stress, was decreased in renal mitochondria in the acute and in heart in the sub-chronic model. Interestingly, alterations of cardiac mitochondrial bioenergetics co-existed with an absence of echocardiograph, histopathological or ultra-structural alterations. Besides, no plasma markers of cardiac injury were found in any of the time points studied. The results confirm that alterations of mitochondrial function, which are more evident in the heart, are an early marker of DOX-induced toxicity, existing even in the absence of cardiac functional alterations.

Mitochondrionopathy Phenotype in Doxorubicin-Treated Wistar Rats Depends on Treatment Protocol and Is Cardiac-Specific

PubMed Central

Pereira, Gonçalo C.; Pereira, Susana P.; Pereira, Claudia V.; Lumini, José A.; Magalhães, José; Ascensão, António; Santos, Maria S.; Moreno, António J.; Oliveira, Paulo J.

2012-01-01

Although doxorubicin (DOX) is a very effective antineoplastic agent, its clinical use is limited by a dose-dependent, persistent and cumulative cardiotoxicity, whose mechanism remains to be elucidated. Previous works in animal models have failed to use a multi-organ approach to demonstrate that DOX-associated toxicity is selective to the cardiac tissue. In this context, the present work aims to investigate in vivo DOX cardiac, hepatic and renal toxicity in the same animal model, with special relevance on alterations of mitochondrial bioenergetics. To this end, male Wistar rats were sub-chronically (7 wks, 2 mg/Kg) or acutely (20 mg/Kg) treated with DOX and sacrificed one week or 24 hours after the last injection, respectively. Alterations of mitochondrial bioenergetics showed treatment-dependent differences between tissues. No alterations were observed for cardiac mitochondria in the acute model but decreased ADP-stimulated respiration was detected in the sub-chronic treatment. In the acute treatment model, ADP-stimulated respiration was increased in liver and decreased in kidney mitochondria. Aconitase activity, a marker of oxidative stress, was decreased in renal mitochondria in the acute and in heart in the sub-chronic model. Interestingly, alterations of cardiac mitochondrial bioenergetics co-existed with an absence of echocardiograph, histopathological or ultra-structural alterations. Besides, no plasma markers of cardiac injury were found in any of the time points studied. The results confirm that alterations of mitochondrial function, which are more evident in the heart, are an early marker of DOX-induced toxicity, existing even in the absence of cardiac functional alterations. PMID:22745682

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

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

PubMed

Afolabi, Saheed O; Akindele, Abidemi J; Awodele, Olufunsho; Anunobi, Chidozie C; Adeyemi, Olufunmilayo O

2012-06-28

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. 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. 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. 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.

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

NASA Astrophysics Data System (ADS)

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

2015-11-01

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Toxicity of Carbon Nanotubes in the Lungs of Mice 7 and 90 Days After Intratracheal Instillation

NASA Technical Reports Server (NTRS)

Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

2002-01-01

Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

Hemlock alkaloids from Socrates to poison aloes.

PubMed

Reynolds, Tom

2005-06-01

Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous plant. Toxicity is due to a group of piperidine alkaloids of which the representative members are coniine and gamma-coniceine. The latter is the more toxic and is the first formed biosynthetically. Its levels in relation to coniine vary widely according to environmental conditions and to provenance of the plants. Surprisingly, these piperidine alkaloids have turned up in quite unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for instance, important medicinal plants, are not regarded as poisonous although some species are very bitter. Nevertheless a small number of mostly local species contain the alkaloids, especially gamma-coniceine and there have been records of human poisoning. The compounds are recognized by their characteristic mousy smell. Both acute and chronic symptoms have been described. The compounds are neurotoxins and death results from respiratory failure, recalling the effects of curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal malformation. Both acute and chronic toxicity are seen with stock in damp meadows and have been recorded as problems especially in North America. The alkaloids derive biosynthetically from acetate units via the polyketide pathway in contrast to other piperidine alkaloids which derive from lysine.

Ecotoxicity in the Reconquista River, province of Buenos Aires, Argentina: a preliminary study.

PubMed

Herkovits, J; Perez-Coll, C S; Herkovits, F D

1996-02-01

The Reconquista River in Argentina is considered a "supercritical" river basin due to environmental degradation. Within its valley of 1.547 km2, there are more than 3 million inhabitants and 12,000 industries. Using early-life-stage toxicity tests with Bufo arenarum embryos (the most sensitive of three native species), we determined the water quality at six sampling stations of the river valley and expressed the results as acute and chronic toxicity units. Along most of the river, the toxicity was higher than the allowable level of whole industrial effluent toxicity recommended by U.S. EPA. In a tributary stream, Arroyo Moron, the water was about 10 times more toxic than the criteria maximum concentration (CMC) recommended by U.S. EPA for industrial effluents. Similar degradation of the water quality was found taking as a reference value an upstream sampling station. In all places where the water quality was worse than the CMC, no macroorganisms were found, and in one of these places, a large number of dead fishes was observed. Our study points out that amphibian early-life-stage toxicity tests could be appropriate for assessing water contamination and water quality, which is essential for diagnosis, protection of environmental services, monitoring, and restoration purposes.

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice

USDA-ARS?s Scientific Manuscript database

Chronic alcohol consumption is detrimental to bone by decreasing bone mineral density (BMD) resulting in increased risk of osteoporosis risk and fracture, particularly in women. In moderation, alcohol is positively associated with increased BMD and reduced fracture risk. Alcohol's toxic effects ha...

Toxic effects of NH4+-N on embryonic development of Bufo gargarizans and Rana chensinensis.

PubMed

Deng, Hongzhang; Chai, Lihong; Luo, Pingping; Zhou, Meimei; Nover, Daniel; Zhao, Xiaohong

2017-09-01

Although nitrogen fertilizer is commonly used worldwide, little information is currently available about NH 4 + -N toxicity on amphibians. This study determined the acute and chronic toxic effects of NH 4 + -N on two native Chinese amphibian species (Bufo gargarizans and Rana chensinensis), and compared the negative sensitivity of different embryos to NH 4 + -N. Static renewal aqueous exposures were performed using B. gargarizans and R. chensinensis embryos at Gosner stage 2 over 96 h. In terms of 96 h-LC 50 , B. gargarizans and R. chensinensis embryos had significantly different responses to NH 4 + -N, and the latter was more sensitive to NH 4 + -N than the former. In the chronic toxicity test, exposure to 10 mg L -1 NH 4 + -N or higher significantly decreased the hatching rate of embryos in both species. Significant increases in the abnormality rate of embryos at 50 mg L -1 NH 4 + -N or higher were observed and morphological abnormalities were characterized by axial flexures, yolk sac edema, and hyperplasia in both species. Additionally, the total length of embryos decreased in a dose-dependent manner after exposure to NH 4 + -N. The results indicate that NH 4 + -N exposure can increase abnormality and inhibit the hatching and development of embryos in B. gargarizans and R. chensinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of chronic toxicities between brachytherapy-based accelerated partial breast irradiation and whole breast irradiation using intensity modulated radiotherapy.

PubMed

Wobb, Jessica L; Shah, Chirag; Jawad, Maha S; Wallace, Michelle; Dilworth, Joshua T; Grills, Inga S; Ye, Hong; Chen, Peter Y

2015-12-01

Brachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities. 1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale. Median follow-up was 4.6 years (range 0.1-13.4) for WBI-IMRT versus 6.7 years (range 0.1-20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups. With 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

PubMed

Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

2016-04-01

Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs.

PubMed

Wu, Kuei-Meng; Yao, Jiaqin; Boring, Daniel

2011-02-01

Recent chronic toxicity studies performed on green tea extracts in fasted dogs have revealed some unique dose-limiting lethal liver, gastrointestinal, and renal toxicities. Key findings included necrosis of hepatic cells, gastrointestinal epithelia and renal tubules, atrophy of reproductive organs, atrophy and necrosis of hematopoietic tissues, and associated hematological changes. The polyphenol cachetins (a mixture of primarily epigallocatechin gallate [≥55%]; plus up to 10% each of epigallocatechin, epicatechin, and epigallocatechin gallate) appeared to be the causative agents for the observed toxicities because they are the active ingredients of green tea extract studied. Conduct of the study in nonfasted dogs under the same testing conditions and dose levels showed unremarkable results. Assuming both studies were valid, at the identified no observed adverse effect levels (NOAEL) of each study, systemic exposures (based on area under the curve [AUC]) were actually lower in fasted than nonfasted dogs, suggesting that fasting may have rendered the target organ systems potentially more vulnerable to the effects of green tea extract. The toxicity mechanisms that produced lethality are not known, but the results are scientifically intriguing. Because tea drinking has become more popular in the United States and abroad, the mode of action and site of action of green tea extract-induced lethal toxicities during fasting and the role of other phytochemical components of Folia Camellia sinensis (including nonpolyphenol fractions, which are often consumed when whole-leaf products are presented) warrant further investigation.

Impact of Environmentally Based Chemical Hardness on Uranium Speciation and Toxicity in Six Aquatic Species

PubMed Central

Goulet, Richard R; Thompson, Patsy A; Serben, Kerrie C; Eickhoff, Curtis V

2015-01-01

Treated effluent discharge from uranium (U) mines and mills elevates the concentrations of U, calcium (Ca), magnesium (Mg), and sulfate (SO42–) above natural levels in receiving waters. Many investigations on the effect of hardness on U toxicity have been experiments on the combined effects of changes in hardness, pH, and alkalinity, which do not represent water chemistry downstream of U mines and mills. Therefore, more toxicity studies with water chemistry encountered downstream of U mines and mills are necessary to support predictive assessments of impacts of U discharge to the environment. Acute and chronic U toxicity laboratory bioassays were realized with 6 freshwater species in waters of low alkalinity, circumneutral pH, and a range of chemical hardness as found in field samples collected downstream of U mines and mills. In laboratory-tested waters, speciation calculations suggested that free uranyl ion concentrations remained constant despite increasing chemical hardness. When hardness increased while pH remained circumneutral and alkalinity low, U toxicity decreased only to Hyalella azteca and Pseudokirchneriella subcapitata. Also, Ca and Mg did not compete with U for the same uptake sites. The present study confirms that the majority of studies concluding that hardness affected U toxicity were in fact studies in which alkalinity and pH were the stronger influence. The results thus confirm that studies predicting impacts of U downstream of mines and mills should not consider chemical hardness. PMID:25475484

Environmental exposures of trace elements assessed using keratinized matrices from patients with chronic kidney diseases of uncertain etiology (CKDu) in Sri Lanka.

PubMed

Diyabalanage, Saranga; Fonseka, Sanjeewani; Dasanayake, D M S N B; Chandrajith, Rohana

2017-01-01

An alarming increase in chronic kidney disease with unknown etiology (CKDu) has recently been reported in several provinces in Sri Lanka and chronic exposures to toxic trace elements were blamed for the etiology of this disease. Keratinized matrices such as hair and nails were investigated to determine the possible link between CKDu and toxic element exposures. Elements Li, B, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Ba, Hg and Pb of hair and nails of patients and age that matched healthy controls were determined with Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results showed that trace element contents in the hair of patients varies in the order of Zn>Fe>Al>Mn>Cu>Ba>Sr>Ni>Pb>Cr>B>Hg>Se>Mo>Co>As>Li>Cd while Fe>Al>Zn>Ni>Cu>Mn>Cr>Ba>Sr>B>Pb>Se>Mo>Co>Hg>Li>As>Cd in nail samples. The hair As levels of 0.007-0.165μgg -1 were found in CKDu subjects. However, no significant difference was observed between cases and controls. The total Se content in hair of CKDu subjects ranged from 0.043 to 0.513μgg -1 while it was varied from 0.031 to 1.15μgg -1 in controls. Selenium in nail samples varied from 0.037μgg -1 to 4.10μgg -1 in CKDu subjects and from 0.042μgg -1 to 2.19μgg -1 in controls. This study implies that substantial proportions of Sri Lankan population are Se deficient irrespective of gender, age and occupational exposure. Although some cutaneous manifestations were observed in patient subjects, chemical analyses of hair and nails indicated that patients were not exposed to toxic levels of arsenic or the other studied toxic elements. Therefore the early suggested causative factors such as exposure to environmental As and Cd, can be ruled out. Copyright © 2016 Elsevier GmbH. All rights reserved.

Toxicity and bioaccumulation of sediment-associated contaminants using freshwater invertebrates: A review of methods and applications

USGS Publications Warehouse

Ingersoll, C.G.; Ankley, G.T.; Benoit, D.A.; Brunson, E.L.; Burton, G.A.; Dwyer, F.J.; Hoke, R.A.; Landrum, P.F.; Norberg-King, T. J.; Winger, P.V.

1995-01-01

This paper reviews recent developments in methods for evaluating the toxicity and bioaccumulation of contaminants associated with freshwater sediments and summarizes example case studies demonstrating the application of these methods. Over the past decade, research has emphasized development of more specific testing procedures for conducting 10-d toxicity tests with the amphipod Hyalella azteca and the midge Chironomus tentans. Toxicity endpoints measured in these tests are survival for H. azteca and survival and growth for C. tentans. Guidance has also been developed for conducting 28-d bioaccumulation tests with the oligochaete Lumbriculus variegatus, including determination of bioaccumulation kinetics for different compound classes. These methods have been applied to a variety of sediments to address issues ranging from site assessments to bioavailability of organic and inorganic contaminants using field-collected and laboratory-spiked samples. Survival and growth of controls routinely meet or exceed test acceptability criteria. Results of laboratory bioaccumulation studies with L. variegatus have been confirmed with comparisons to residues (PCBs, PAHs, DDT) present from synoptically collected field populations of oligochaetes. Additional method development is currently underway to develop chronic toxicity tests and to provide additional data-confirming responses observed in laboratory sediment tests with natural benthic populations.

Refining methods for conducting long-term sediment and water toxicity tests with Chironomus dilutus: Formation of a midge chronic testing work group

EPA Science Inventory

Standard methods have been established by USEPA, ASTM International, Environment Canada and Organization for Economic Cooperation and Development for conducting sediment toxicity tests with various species of midges including Chironomus dilutus. Short-term 10-day exposures are ty...

Metabolomics of microliter hemolymph samples enables an improved understanding of the combined metabolic and transcriptional responses of Daphnia magna to cadmium

EPA Science Inventory

Cadmium is a toxic metal causing sublethal and chronic effects in crustaceans. Omic technologies offer unprecedented opportunities to better understand modes of toxicity by providing a holistic view of the molecular changes underlying physiological disruption. We sought to use ge...

RELATIONSHIPS OF QUANTITATIVE STRUCTURE-ACTIVITY TO COMPARATIVE TOXICITY OF SELECTED PHENOLS IN THE 'PIMEPHALES PROMELAS' AND 'TETRAHYMENA PYRIFORMIS' TEST SYSTEMS

EPA Science Inventory

The relative toxic response of 27 selected phenols in the 96-hr acute flowthrough Pimephales promelas (fathead minnow) and the 48- to 60-hr chronic static Tetrahymena pyriformis (ciliate protozoan) test systems was evaluated. Log Kow-dependent linear regression analyses revealed ...

Toxicity of TNT Wastewaters to Aquatic Organisms. Volume 2. Acute Toxicity of Condensate Wastewater and 2,4-Dinitrotoluene

DTIC Science & Technology

1983-03-01

Gambusia affinis (mosquito fish) and reported a 96-hour LC50 of 1180 mg/L. In tests with Daplnia maa (invertebrate) and Scenedesmus sp. (alga), Bringmann...chronic bioassays be performed. )AM Bringmann and Kuhn (1980) evaluated the response of bacteria (Pseudomonas putid, algae ( Scenedesmus quadricauda

Imidacloprid toxicity impairs spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas.

PubMed

Hsiao, Chun-Jen; Lin, Ching-Lung; Lin, Tian-Yu; Wang, Sheue-Er; Wu, Chung-Hsin

2016-04-13

It has been reported that the decimation of honey bees was because of pesticides of imidacloprid. The imidacloprid is a wildly used neonicotinoid insecticide. However, whether imidacloprid toxicity interferes with the spatial memory of echolocation bats is still unclear. Thus, we compared the spatial memory of Formosan leaf-nosed bats, Hipposideros terasensis, before and after chronic treatment with a low dose of imidacloprid. We observed that stereotyped flight patterns of echolocation bats that received chronic imidacloprid treatment were quite different from their originally learned paths. We further found that neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas of echolocation bats that received imidacloprid treatment was significantly enhanced in comparison with echolocation bats that received sham treatment. Thus, we suggest that imidacloprid toxicity may interfere with the spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas. The results provide direct evidence that pesticide toxicity causes a spatial memory disorder in echolocation bats. This implies that agricultural pesticides may pose severe threats to the survival of echolocation bats.

Effects of diamond nanoparticle exposure on the internal structure and reproduction of Daphnia magna.

PubMed

Mendonça, Elsa; Diniz, Mário; Silva, Luís; Peres, Isabel; Castro, Luísa; Correia, José Brito; Picado, Ana

2011-02-15

Nanomaterials have significant technological advantages but their release into the environment also carry potential ecotoxicological risks. Carbon-based nanoparticles and particularly diamond nanoparticles have numerous industrial and medical applications. The aim of the present study was to evaluate the toxic effects of diamond nanoparticles with an average particle size of 20 nm on the survival, reproduction and tissue structure of the freshwater crustacean Daphnia magna. The chronic toxicity test results showed 100% mortality at concentrations higher than 12.5 mg l(-1) and that reproduction inhibition occurred in concentrations higher than 1.3 mg l(-1). Light microscopy showed that diamond nanoparticles adhere to the exoskeleton surface and accumulate within the gastrointestinal tract, suggesting that food absorption by the gut cells may be blocked. The results support the use of chronic approaches in environmental protection as part of an integrated environmental monitoring and assessment strategy. Copyright © 2010 Elsevier B.V. All rights reserved.

An Update on ToxCast™ | Science Inventory | US EPA

EPA Pesticide Factsheets

In its first phase, ToxCast™ is profiling over 300 well-characterized chemicals (primarily pesticides) in over 400 HTS endpoints. These endpoints include biochemical assays of protein function, cell-based transcriptional reporter assays, multi-cell interaction assays, transcriptomics on primary cell cultures, and developmental assays in zebrafish embryos. Almost all of the compounds being examined in Phase 1 of ToxCast™ have been tested in traditional toxicology tests, including developmental toxicity, multi-generation studies, and sub-chronic and chronic rodent bioassays Lessons learned to date for ToxCast: Large amounts of quality HTS data can be economically obtained. Large scale data sets will be required to understand potential for biological activity. Value in having multiple assays with overlapping coverage of biological pathways and a variety of methodologies Concentration-response will be important for ultimate interpretation Data transparency will be important for acceptance. Metabolic capabilities and coverage of developmental toxicity pathways will need additional attention. Need to define the gold standard Partnerships are needed to bring critical mass and expertise.

Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

PubMed

Skinner, Roderick

2018-02-01

Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

Acute and chronic effects of four commercial herbicide formulations on Ceriodaphnia dubia

USGS Publications Warehouse

Ort, M. P.; Fairchild, J.F.; Finger, S.E.

1994-01-01

Toxicity tests with Ceriodaphnia dubia were conducted to determine acute (48 h) and chronic (7-day survival and reproduction) effects of four commonly used herbicide formulations. The 48-h LC50s in decreasing order of toxicity were 14.36 mg/L (Micro-Tech®), 15.93 mg/L (Bicep®), 32.99 mg/L (Extrazine®), and 35.36 mg/L (Lexone®). Reduced reproduction was detected at concentrations below 48-h LC50s for three of the formulations. The 7-day chronic values (ChV) based on reproduction were 17.68 mg/L (Micro-Tech®), 8.84 mg/L (Bicep®), 17.68 mg/L (Extrazine®), and 8.84 mg/L (Lexone®). The acute-to-chronic ratios (ACRs) for Micro-Tech® (0.81), Bicep® (1.80), Extrazine® (1.86), and Lexone® (4.00) indicate a relatively narrow range between acute and chronic sensitivity in daphnids. A comparison of these response data to environmental concentrations suggests these herbicides are not likely to directly impact invertebrates. Potential impacts on plants and human health should be of primary ecological and regulatory concern.

Nonnarcotic analgesics and tricyclic antidepressants for the treatment of chronic nonmalignant pain.

PubMed

Richlin, D M

1991-05-01

Chronic nonmalignant pain is often characterized by multiple treatment failures, a pattern of maladaptive behavior, and depression. Often there is a history of inappropriate and excessive use of medications for pain. Prior and ongoing use of narcotics and sedatives acts to compound and aggravate the chronic pain syndrome. A first step in treatment is controlled withdrawal of these agents. Nonnarcotic analgesics, NSAIDs, and tricyclic antidepressants are commonly employed in patients with chronic pain. Effective use of these agents requires understanding of their pharmacokinetic and pharmacodynamic properties. Use of a fixed-time schedule is necessary to achieve an effective, sustained therapeutic response. Careful patient education and monitoring for side effects and toxicity are necessary, particularly in the elderly and patients with coexisting medical disorders. Incidence of side effects and toxicity may be reduced by choice of drug and modification of dosing regimen. Nonnarcotic analgesics, TCAs, and NSAIDs are seldom effective by themselves in resolving the pain and distress of patients with chronic nonmalignant pain. This is particularly true when maladaptive behavior coexists. A comprehensive multimodal pain management program encompassing additional pain-relieving strategies and behavior-modifying techniques should be considered and utilized in conjunction with medication.

Toxicity of inorganic and organic selenium to Daphnia magna (cladocera) and Chironomus riparius (diptera)

USGS Publications Warehouse

Ingersoll, Christopher G.; Dwyer, F.J.; May, T.W.

1990-01-01

Elevated concentrations of selenium (Se) have been previously measured in biota sampled from the Kesterson National Wildlife Refuge (KNWR) in the San Joaquin Valley of central California. We conducted acute and chronic toxicity tests with the cladoceran Daphnia magna and the midge Chironomus riparius to determine the toxicity or bioaccumulation of waterborne Se in a reconstituted water similar to the San Joaquin River. Daphnids were more acutely sensitive than midges to the toxic effects of inorganic Se. An organic form of Se (seleno-[L]-methionine) was extremely toxic to daphnids, but was relatively nontoxic to midges. In long-term exposure to a 6:1 mixture of selenate to selenite (a mixture representative of KNWR), the emergence time of adult midges was delayed at Se concentrations ≥ 837 μg/L. Daphnid reproduction and intrinsic rate of natural increase (r) were reduced at Se concentrations ≥ 348 μg/L and growth of adults was reduced at ≥ 156 μg/L. Whole body Mg, K and Na concentrations in daphnids were not affected by chronic Se exposure; however, whole body Ca concentration increased at intermediate Se exposure concentrations. In addition, whole body Cl concentration was reduced at 711 μg Se/L. Daphnids accumulated potentially toxic concentrations of Se from water that may adversely affect fish or waterfowl through the food chain.

The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge.

PubMed

Gelpí, Emilio; de la Paz, Manuel Posada; Terracini, Benedetto; Abaitua, Ignacio; de la Cámara, Agustín Gómez; Kilbourne, Edwin M; Lahoz, Carlos; Nemery, Bénoit; Philen, Rossanne M; Soldevilla, Luis; Tarkowski, Stanislaw

2002-05-01

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization's Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated.

The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge.

PubMed Central

Gelpí, Emilio; de la Paz, Manuel Posada; Terracini, Benedetto; Abaitua, Ignacio; de la Cámara, Agustín Gómez; Kilbourne, Edwin M; Lahoz, Carlos; Nemery, Bénoit; Philen, Rossanne M; Soldevilla, Luis; Tarkowski, Stanislaw

2002-01-01

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization's Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated. PMID:12003748

Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice.

PubMed Central

Dieter, M P

1994-01-01

Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889889

An 'injury-time integral' model for extrapolating from acute to chronic effects of phosgene.

PubMed

Hatch, G; Kodavanti, U; Crissman, K; Slade, R; Costa, D

2001-06-01

The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the 'concentrationxtime' (CxT) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (male Fischer 344) were exposed (six hours/day) to air or 0.1, 0.2, 0.5 and 1.0 ppm of phosgene one time or on a repeated regimen for up to 12 weeks as follows: 0.1 ppm (five days/week), 0.2 ppm (five days/week), 0.5 ppm (two days/week), or 1.0 ppm (one day/week) (note that the CxT for the three highest exposures was the same). Animals were sacrificed at 4, 8, and 12 weeks during the exposure and after four weeks recovery. Bronchoalveolar lavage (BAL) was performed 18 hours after the last exposure for each time period and the BAL supernatant assayed for protein. Elevated BAL fluid protein was defined as 'acute injury', diminished response after repeated exposure was defined as 'adaptation', and increased lung hydroxyproline or trichrome staining for collagen was defined as 'chronic injury'. Results indicated that exposures that cause maximal chronic injury involve high exposure concentrations and longer times between exposures, not high CxT products. A conceptual model is presented that explains the lack of CxT correlation by the fact that adaptation reduces an 'injury-time integral' as phosgene exposure is lengthened from acute to subchronic. At high exposure concentrations, the adaptive response appears to be overwhelmed, causing a continued injury-time integral, which appears to be related to appearance of chronic injury. The adaptive response is predicted to disappear if the time between exposures is lengthened, leading to a continued high injury-time integral and chronic injury. It has generally been assumed that long, continuous exposures of rodents is a conservative approach for detecting possible chronic effects. The present study suggests that such an approach my not be conservative, but might actually mask effects that could occur under intermittent exposure conditions.

Determination of the Chronic Mammalian Toxicological Effects of TNT. Twenty-Six Week Subchronic Oral Toxicity Study of Trinitrotoluene (TNT) in the Beagle Dog.

DTIC Science & Technology

1983-06-01

41 +1 +1 .9 +9 +1 41 -4 o o 1.- I - - Cl C 103 .1 . 5 11 . +1 +1 +1 +1 -nIn 0 In (D 02 0 . 1 + 5 +1 +1 +1 +9 1 +1 +1 0 W 0 *Z to~ 1w 0 0 W I.-I .j I U...SPERFORMING ORG. REPORT NUMBERTwenty-Six Week Subchronic Oral Toxicity Study of 11 StdyNor Trinitrotoluene (TNT) in The Beagle On IL11 COSATRGAtd NoM. 5 ...in the present studya7 Unclassified TV - CL ASSI FIAINO THIS P AGC(Ht.M Dat Eteed Contract No., DAND17-79-C-9120 IITRI Project No. L6116 Study No. 5

Challenges in the Clinical Application of the American Society of Clinical Oncology Value Framework: A Medicare Cost-Benefit Analysis in Chronic Lymphocytic Leukemia.

PubMed

Seymour, Erlene K; Schiffer, Charles A; de Souza, Jonas A

2017-12-01

The ASCO Value Framework calculates the value of cancer therapies. Given costly novel therapeutics for chronic lymphocytic leukemia, we used the framework to compare net health benefit (NHB) and cost within Medicare of all regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines. The current NCCN guidelines for chronic lymphocytic leukemia were reviewed. All referenced studies were screened, and only randomized controlled prospective trials were included. The revised ASCO Value Framework was used to calculate NHB. Medicare drug pricing was used to calculate the cost of therapies. Forty-nine studies were screened. The following observations were made: only 10 studies (20%) could be evaluated; when comparing regimens studied against the same control arm, ranking NHB scores were comparable to their preference in guidelines; NHB scores varied depending on which variables were used, and there were no clinically validated thresholds for low or high values; treatment-related deaths were not weighted in the toxicity scores; and six of the 10 studies used less potent control arms, ranked as the least-preferred NCCN-recommended regimens. The ASCO Value Framework is an important initial step to quantify value of therapies. Essential limitations include the lack of clinically relevant validated thresholds for NHB scores and lack of incorporation of grade 5 toxicities/treatment-related mortality into its methodology. To optimize its application for clinical practice, we urge investigators/sponsors to incorporate and report the required variables to calculate the NHB of regimens and encourage trials with stronger comparator arms to properly quantify the relative value of therapies.

Tissue distributions of fluoride and its toxicity in the gills of a freshwater teleost, Cyprinus carpio.

PubMed

Cao, Jinling; Chen, Jianjie; Wang, Jundong; Wu, Xiangtian; Li, Yundong; Xie, Lingtian

2013-04-15

Fish take up fluoride directly from water and are susceptible to fluoride contamination of their environment. In this study, we examined the tissue distributions of fluoride and its toxicity in the gills of the common carp (Cyprinus carpio) chronically exposed to fluoride. Carp were exposed to a range of aqueous fluoride (35-124 mg/L) and sampled at 30, 60 and 90 days. The accumulation of fluoride in the tissues increased with the level and duration of exposure. Steady state was not achieved under the experimental conditions. The gills accumulated the highest levels of fluoride followed by the liver>brain>kidney>muscle>intestine. A dose-dependent inhibition was observed for the enzyme activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase in the gills after the fish were exposed for 90 days. Also, accumulation of fluoride was associated with the inhibition of superoxide dismutase (SOD) activities and a dose-dependent stimulation of malondialdehyde (MDA) levels in the gill tissues, suggesting that fluoride promoted oxidative stress in the fish. Microscopic examinations revealed injuries to gill tissues and chloride cells, with the severity of injury increasing with exposure concentration. These results suggest that chronic exposure to elevated concentrations of fluoride may induce toxicity in the common carp. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

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. © 2015 by The Author(s).

Biological monitoring as proficient assessment method in chronic exposure to irritating gases and vapors.

PubMed

Szász, Zsuzsánna; Abrám, Z; Szász, L; Moldovan, H; Demeter, Annamária

2013-01-01

Air pollution and its adverse health effect represent a global issue. Long term or permanent exposure at low doses of toxic material may increase the number of new appeared severe respiratory diseases and may aggravate most of the existing chronic cases. In the present study, the main toxic aerosols released by the greatest chemical factory in Transylvania were analyzed and their health impacts were measured. We have used in our trial biologic monitoring 1786 employees from a chemical factory in a transversal descriptive study. In the same time, we have noticed environmental determination of air quality and also, we have checked the health status and other 90 cases from a nonchemical factory. In this factory there are also pneumotrop harms. Results of our study give useful information regarding workers health status, with possibility to make pollution-medical condition association: there was no significant association between occurrence of decreased lung function tests and exposure of chemical irritants compared to the second investigated factory. Exposure to pneumotrope hazards imposes safeguards to protect health and biological monitoring has proven absolutely necessary to do so. Last but not least, lifestyle monitoring is to be effective.

Derivation of guideline values for gold (III) ion toxicity limits to protect aquatic ecosystems.

PubMed

Nam, Sun-Hwa; Lee, Woo-Mi; Shin, Yu-Jin; Yoon, Sung-Ji; Kim, Shin Woong; Kwak, Jin Il; An, Youn-Joo

2014-01-01

This study focused on estimating the toxicity values of various aquatic organisms exposed to gold (III) ion (Au(3+)), and to propose maximum guideline values for Au(3+) toxicity that protect the aquatic ecosystem. A comparative assessment of methods developed in Australia and New Zealand versus the European Community (EC) was conducted. The test species used in this study included two bacteria (Escherichia coli and Bacillus subtilis), one alga (Pseudokirchneriella subcapitata), one euglena (Euglena gracilis), three cladocerans (Daphnia magna, Moina macrocopa, and Simocephalus mixtus), and two fish (Danio rerio and Oryzias latipes). Au(3+) induced growth inhibition, mortality, immobilization, and/or developmental malformations in all test species, with responses being concentration-dependent. According to the moderate reliability method of Australia and New Zealand, 0.006 and 0.075 mg/L of guideline values for Au(3+) were obtained by dividing 0.33 and 4.46 mg/L of HC5 and HC50 species sensitivity distributions (SSD) with an FACR (Final Acute to Chronic Ratio) of 59.09. In contrast, the EC method uses an assessment factor (AF), with the 0.0006 mg/L guideline value for Au(3+) being divided with the 48-h EC50 value for 0.60 mg/L (the lowest toxicity value obtained from short term results) by an AF of 1000. The Au(3+) guideline value derived using an AF was more stringent than the SSD. We recommend that more toxicity data using various bioassays are required to develop more accurate ecological risk assessments. More chronic/long-term exposure studies on sensitive endpoints using additional fish species and invertebrates not included in the current dataset will be needed to use other derivation methods (e.g., US EPA and Canadian Type A) or the "High Reliability Method" from Australia/New Zealand. Such research would facilitate the establishment of guideline values for various pollutants that reflect the universal effects of various pollutants in aquatic ecosystems. To the best of our knowledge, this is the first study to suggest guideline values for Au(3+) levels permitted to enter freshwater environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001