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Sample records for acute toxicological effects

  1. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-01-01

    The use of hazardous materials requires the means of assessing doses from postulated accidental exposures to the hazardous materials. Hazardous materials include radiological and toxicological substances. Health effects are often divided into either acute (short term exposure) or chronic (long-term-exposure)-categories. Dose assessments and health effects are used in Hazard Classification, Safety Analysis Reports and Unreviewed Safety Question Determinations. The use of hazardous substances requires a means of assessing the potential health effects from exposure. Two types of toxicological data exist. The first is measured effects from human exposure, either accidentally or studies. The second consists of data from toxicity and lethality studies on mammals, often mice or rats. Because the data for human exposure is severely limited, an approach is needed that uses basic toxicity and lethality data from animal studies to estimate acute health effects in humans. The approach chosen is the one suggested jointly by the EPA, FEMA, and DOT in their Technical Guidance for Hazards Analysis'', December 1987.

  2. Toxicological dose assessment and acute health effect criteria

    SciTech Connect

    Stalker, A.C.; White, B.

    1992-09-01

    The use of hazardous materials requires the means of assessing doses from postulated accidental exposures to the hazardous materials. Hazardous materials include radiological and toxicological substances. Health effects are often divided into either acute (short term exposure) or chronic (long-term-exposure)-categories. Dose assessments and health effects are used in Hazard Classification, Safety Analysis Reports and Unreviewed Safety Question Determinations. The use of hazardous substances requires a means of assessing the potential health effects from exposure. Two types of toxicological data exist. The first is measured effects from human exposure, either accidentally or studies. The second consists of data from toxicity and lethality studies on mammals, often mice or rats. Because the data for human exposure is severely limited, an approach is needed that uses basic toxicity and lethality data from animal studies to estimate acute health effects in humans. The approach chosen is the one suggested jointly by the EPA, FEMA, and DOT in their ``Technical Guidance for Hazards Analysis``, December 1987.

  3. Acute toxicological effects on the earthworm Eisenia fetida of 18 common pharmaceuticals in artificial soil.

    PubMed

    Pino, Ma Rosa; Val, Jonatan; Mainar, Ana Ma; Zuriaga, Estefanía; Español, Cecilia; Langa, Elisa

    2015-06-15

    Following soil applications of recycled water and biosolids, pharmaceutical residues can eventually enter the terrestrial environment. In vitro and in vivo assays have largely focused on the acute ecotoxicity of these compounds in aquatic systems. However, studies on the ecotoxicological effects of pharmaceuticals in soil biota are especially scarce. The aim of this study was to investigate the acute toxicity of 18 pharmaceuticals (4 NSAIDs, 5 blood lipid-lowering agents, 6 β-blockers and 3 antibiotics) that are usually found in the environment by using an Eisenia fetida bioassay. In addition, the presence of these pharmaceuticals in artificial soil was verified at the end of the test. Our results indicate that seven of the studied drugs cause acute adverse effects in E. fetida, in particular, the NSAIDs and the blood lipid-lowering agents. Ibuprofen (LC50=64.80 mg/kg) caused the highest acute toxicity for all tested compounds, followed by diclofenac (LC50=90.49 mg/kg) and simvastatin (LC50=92.70 mg/kg). Other tested pharmaceuticals from NSAIDs and blood lipid-lowering families have toxicity effects, from a LC50=140.87 mg/kg for gemfibrozil to 795.07 mg/kg for lovastatin. Atorvastatin, bezafibrate, β-blockers and antibiotics showed no detectable lethality in E. fetida. The four NSAIDs showed evidence of modification of their original chemical structure after 14 days so the detected toxicity may be due to the original product as well as their degradation products. The three blood lipid-lowering agents seem to be more stable in soil. From an environmental perspective, the lethal concentrations of the tested drugs are much greater than those reported in wastewater and biosolids, therefore acute toxic effects may be improbable. However, little is known about the accumulation of these substances in soils after regular applications, so accumulative and chronic effects cannot be excluded. Moreover, more studies are needed to determine the role of the degradation

  4. [Acute toxicological effects of heavy metal pollution in soils on earthworms].

    PubMed

    Song, Yufang; Zhou, Qixing; Xu, Huaxia; Ren, Liping; Sun, Tieheng; Gong, Ping

    2002-02-01

    Acute and sub-acute lethal effects of single and combined Cu, Zn, Pb and Cd on earthworm was determined using meadow brown soil. Results indicated that the mortality of earthworm was significantly related with the concentrations of Cu and Zn in the soil (alpha = 0.05, RCu = 0.86, RPb = 0.87), and the inhibition rate of earthworm growth was significantly related with the concentration of Cu in the soil (alpha = 0.05, RCu = 0.84). There was no significant relation between the concentrations of other heavy metals tested and the death rate and the growth-inhibition rate. The degree of individual earthworm enduring the toxicity of heavy metals varied greatly. The threshold concentration of toxicity defined by statistical method, the level to conduce the death of individual earthworm was 300 mg.kg-1 for Cu, 1300 mg.kg-1 for Zn, 1700 mg.kg-1 for Pb, 300 mg.kg-1 for Cd. LC50 was 400-450 mg.kg-1 for Cu, 1500-1900 mg.kg-1 for Zn, 2350-2400 mg.kg-1 for Pb and 900 mg.kg-1 for Cd. Combined effects of single Cu, Zn, Pb and Cd to conduce more than 10% of the death rate of earthworm could result in 100% of the death rate of earthworm, thus showing the strong synergistic joint effect of the heavy metals. PMID:11993124

  5. Acute toxicology of components of vegetation smoke

    SciTech Connect

    Dost, F.N. )

    1991-01-01

    Only in recent times, systematic attention has been paid to the occupational health of forest firefighters and workers who manage prescribed fire. Two parts of the effort to learn the impact on worker health are medical observation of those workers, and study of occupational hygiene. It is also necessary to learn what components of smoke are most likely to affect firefighters, and to learn something of the manner in which those substances might compromise health; this review is a step toward that end. The number of possible products of vegetation combustion is almost limitless, and every fuel and condition of burning produces a unique pattern. Nonetheless, it is possible and practical to select a limited number of products that are most likely to be involved in the acute toxicity of smoke. Two products that are almost certainly important are formaldehyde and acrolein. Both appear to occur in all smoke. The toxicology of both is well studied; in particular both are powerful mucosal irritants. Estimates of exposure suggest strongly that concentrations are high enough in smoke to contribute some or all of the irritant activity. There seems to be a reasonable prospect that free radical precursors with half-lives in the tens of minutes are produced when cellulosic materials burn. If so, they will reach the respiratory tract, and liberate free radicals that react immediately on or in pulmonary cells. Ozone is not produced in the fire, but the various hydrocarbons of smoke are substrates for reactions that eventually produce ozone, and that production may continue for miles down-plume. Some measured plume concentrations approach the threshold for human health effects. The effects of the best known component, the particulate material, are unknown in isolation from all of the other substances in smoke. 122 refs.

  6. Acute toxicology of components of vegetation smoke.

    PubMed

    Dost, F N

    1991-01-01

    Only in recent times, systematic attention has been paid to the occupational health of forest firefighters and workers who manage prescribed fire. Two parts of the effort to learn the impact on worker health are medical observation of those workers, and study of occupational hygiene. It is also necessary to learn what components of smoke are most likely to affect firefighters, and to learn something of the manner in which those substances might compromise health; this review is a step toward that end. The number of possible products of vegetation combustion is almost limitless, and every fuel and condition of burning produces a unique pattern. Nonetheless, it is possible and practical to select a limited number of products that are most likely to be involved in the acute toxicity of smoke. Two products that are almost certainly important are formaldehyde and acrolein. Both appear to occur in all smoke. The toxicology of both is well studied; in particular both are powerful mucosal irritants. Estimates of exposure suggest strongly that concentrations are high enough in smoke to contribute some or all of the irritant activity. There seems to be a reasonable prospect that free radical precursors with half-lives in the tens of minutes are produced when cellulosic materials burn. If so, they will reach the respiratory tract, and liberate free radicals that react immediately on or in pulmonary cells. Ozone is not produced in the fire, but the various hydrocarbons of smoke are substrates for reactions that eventually produce ozone, and that production may continue for miles down-plume. Some measured plume concentrations approach the threshold for human health effects. The effects of the best known component, the particulate material, are unknown in isolation from all of the other substances in smoke. In spite of that ignorance, particulate loading is the principal index of smoke pollution for regulatory purposes, and sometimes is incorrectly used to represent smoke

  7. Quantification of toxicological effects for dichloromethane. Draft report (Final)

    SciTech Connect

    Not Available

    1990-04-01

    The source documents for background information used to develop the report on the quantification of toxicological effects for dichloromethane are the health assessment document (HAD) for dichloromethane and a subsequent addendum to the HAD (U.S. EPA, 1985b). In addition, some references published since 1985 are discussed. To summarize the results of the quantification of toxicological effects, a One-day Health Advisory of 10,000 ug/L for a 10-kg child was calculated, based on an acute oral study in rats reported by Kimura et al. (1971). No suitable data for the derivation of a Ten-day Health Advisory were found in the available literature.

  8. Acute Poisoning During Pregnancy: Observations from the Toxicology Investigators Consortium.

    PubMed

    Zelner, Irene; Matlow, Jeremy; Hutson, Janine R; Wax, Paul; Koren, Gideon; Brent, Jeffrey; Finkelstein, Yaron

    2015-09-01

    Acute poisonings during pregnancy pose a particular challenge to health care providers because of the potential for an immediate life threat or possible life-long implications for both the mother and fetus, including teratogenicity of the poison or its antidote. We describe recent consequential exposures among pregnant women in the USA. We identified all poisoning cases involving pregnant women that were catalogued by the medical toxicology services across the 37 sites of the Toxicology Investigators Consortium (ToxIC) Registry of the American College of Medical Toxicology between January 2010 and December 2012. Of 17,529 exposure cases reported in the ToxIC Registry, 103 (0.6 %) involved pregnant women, 80 % of whom were symptomatic and about a quarter displayed a specific toxidrome. The majority of cases (n = 53; 51.5 %) involved intentional exposures, most commonly to pharmaceutical agents, followed by unintentional pharmaceutical exposures (10 %) and withdrawal syndromes (9 %). Non-opioid analgesics were the most common class of agents encountered (31 %), followed by sedative-hypnotics/muscle relaxants (18 %), opioids (17 %), anti-convulsants (10 %), and anti-depressants (10 %). Over a third of cases involved exposure to multiple substances, and 32 % involved exposure to more than one drug class. The most commonly administered antidotes were N-acetylcysteine (23 %), sodium bicarbonate (10 %), flumazenil (4 %), and physostigmine (4 %). About half of acute poisoning cases among pregnant women presenting for emergency care involved intentional exposures, mostly with over-the-counter analgesics and psychoactive medications. Clinicians should be cognizant of the unique circumstances, maternal and fetal risks, and management principles of the acutely poisoned pregnant woman.

  9. Acute arsenic poisoning: clinical, toxicological, histopathological, and forensic features.

    PubMed

    Tournel, Gilles; Houssaye, Cédric; Humbert, Luc; Dhorne, Christine; Gnemmi, Viviane; Bécart-Robert, Anne; Nisse, Patrick; Hédouin, Valéry; Gosset, Didier; Lhermitte, Michel

    2011-01-01

    This report describes a suicide case by acute arsenic intoxication via intravenous injection. A 30-year-old woman injected arsenic As (V) (sodium arseniate disodique: Disodium Hydrogena Arsenik RP) in a successful suicide attempt. Three hours following administration, the woman developed severe digestive symptoms. She was admitted to a hospital and transferred to the intensive care unit within 12 h of the massive administration of arsenic. Despite therapeutic efforts, over the next 2 h she developed multiorgan failure and died. A postmortem examination was performed. Pulmonary edema and congestion of liver were apparent. As (V) and As (III) were determined by high performance liquid chromatography and inductively coupled plasma mass spectrometry after mineralization of samples by concentrated nitric acid. Toxicological analysis revealed high concentrations of arsenic in biological fluids as well as in organs. Histopathological examination showed a typical indication of myocarditis. These findings were in agreement with acute arsenic poisoning. The symptoms developed by this young woman (intoxication by intravenous administration) were comparable to oral intoxication. The clinical signs, survival time, and administration type are discussed in light of the literature on acute and chronic arsenic poisoning.

  10. Toxicological Effects of Fullerenes on Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Schomaker, Justin; Snook, Renee; Howell, Carina

    2014-03-01

    The nematode species Caenorhabditis elegans is a useful genetic model organism due to its simplicity and the substantial molecular, genetic, and developmental knowledge about the species. In this study, this species was used to test the toxicological effects of C60 fullerene nanoparticles. In previous studies using rats, a solution of C60 fullerenes in olive oil proved to extend the life of the subjects. The purpose of this experiment was to subject C. elegans to varying concentrations of C60 fullerenes and observe their toxicological effects. Initial findings indicate a link between fullerene exposure and enlargement of the vulva as well as the formation of a small nodule at the base of the tail in some individuals. While the fullerenes are not lethally toxic in C. elegans, results will be presented that pertain to changes in life span and progeny of the nematodes exposed to varying concentrations of fullerenes as well as the mechanisms of toxicity. High magnification imaging via SEM and/or AFM will be used to characterize the fullerene nanoparticles. Testing the toxicity of fullerenes in a wide variety of organisms will lead to a more complete understanding of the effects of fullerenes on living organisms to ultimately understand their effects in humans. This work was supported by National Science Foundation grants DUE-1058829, DMR-0923047, DUE-0806660 and Lock Haven FPDC grants.

  11. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants.

    PubMed

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a 'high' risk to develop Day Away From Work illness, and lakes that present a 'low' or 'medium' risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.

  12. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants.

    PubMed

    Reichwaldt, Elke S; Stone, Daniel; Barrington, Dani J; Sinang, Som C; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a 'high' risk to develop Day Away From Work illness, and lakes that present a 'low' or 'medium' risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants. PMID:27589798

  13. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

    PubMed Central

    Reichwaldt, Elke S.; Stone, Daniel; Barrington, Dani J.; Sinang, Som C.; Ghadouani, Anas

    2016-01-01

    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants. PMID:27589798

  14. Biosynthesis and toxicological effects of patulin.

    PubMed

    Puel, Olivier; Galtier, Pierre; Oswald, Isabelle P

    2010-04-01

    Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects.

  15. Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

    PubMed

    Bergin, Ingrid L; Wilding, Laura A; Morishita, Masako; Walacavage, Kim; Ault, Andrew P; Axson, Jessica L; Stark, Diana I; Hashway, Sara A; Capracotta, Sonja S; Leroueil, Pascale R; Maynard, Andrew D; Philbert, Martin A

    2016-01-01

    Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity. PMID:26305411

  16. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs

    PubMed Central

    KUE, Chin Siang; TAN, Kae Yi; LAM, May Lynn; LEE, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD50) in the CAM were measured and calculated for these drugs. The resultant ideal LD50 values were correlated to those reported in the literature using Pearson’s correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r2=0.42 − 0.68, P<0.005–0.05) between the ideal LD50 values obtained using the CAM model with LD50 values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  17. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.

    PubMed

    Kue, Chin Siang; Tan, Kae Yi; Lam, May Lynn; Lee, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  18. Acute and sub-acute toxicological assessment of the aqueous seed extract of Persea americana mill (Lauraceae) in rats.

    PubMed

    Ozolua, Raymond I; Anaka, Ogochukwu N; Okpo, Stephen O; Idogun, Sylvester E

    2009-07-03

    The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

  19. Subchronic dispositional and toxicological effects of arsenate administered in drinking water to mice

    SciTech Connect

    Hughes, M.F.; Thompson, D.J.

    1996-10-11

    Exposure to the drinking water contaminant arsenate is a daily occurrence and there are concerns that this exposure may lead to cancer. Although the acute dispositional effects of arsenate have been studied in detail, there is minimal information on the disposition and toxicological effects of it after continuous exposure. The objective of this study was to examine in mice the effect of a 4-wk treatment with arsenate administered in drinking water. Female B6C3F1 mice were housed in metabolism cages and given water and food ad libitum. Two groups (A,B) of mice were treated with distilled water or water containing 0.025 mg/L (L) or 2.5 mg/L (H) arsenate. Several toxicological effects were observed in animals administered arsenate in drinking water, but no changes in the disposition of this arsenical were detected at the doses used in this study. 86 refs., 4 figs., 7 tabs.

  20. Toxicological evaluation of ferrous N-carbamylglycinate chelate: Acute, Sub-acute toxicity and mutagenicity.

    PubMed

    Wan, Dan; Zhou, Xihong; Xie, Chunyan; Shu, Xugang; Wu, Xin; Yin, Yulong

    2015-11-01

    Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD50) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity.

  1. Toxicological effects of nanoparticles from photocopiers

    NASA Astrophysics Data System (ADS)

    Khatri, Madhu

    Nanotechnology is expanding rapidly and its fast-track to commercialization offering highly promising products and materials. Various physical, chemical and biological processes also results in unintentional generation of nanoparticles (NPs) leading to much higher concentrations at certain workplaces. Thus, human exposures to NPs from anthropogenic sources have increased dramatically in the past few decades. Recently, concerns have been expressed about the potential risks to human health occurring due to NP exposures in various workplaces. Although, a few recent studies have shown that the workplace exposure to NPs has the potential to cause serious human health problems such as pulmonary and related cardiovascular diseases, yet the evidence to establish their association is still lacking. This is partly due to lack of easily accessible settings with continuous NP exposures and the unavailability of sufficiently large cohorts of exposed workers. High volume photocopy (PC) centers are common and are generally operated by a permanent staff. It is now well known that laser printers and photocopiers emit NPs. We have observed that photocopiers emit significantly more NPs than laser printers and that the copy center environments had more than 20 times elevated NP levels over the background. It is evident that a significant fraction of airborne NPs get deposited in the alveolar and nasal cavity regions. Therefore, photocopy centers not only offer an opportunity to study response pattern in workers who are chronically exposed to NPs, but also to test and develop necessary methodologies to link exposures to engineered NPs and early health effects. In this study, early human health effects associated with acute NP exposure were studied. This was done by exposing a few health subjects to PC center environment for a short duration and measuring inflammatory and oxidative stress biomarkers in their nasal lavage and urine samples in response to such exposure. Additionally

  2. The acute mammalian toxicology of dibenz(b,f)-1,4-oxazepine.

    PubMed

    Ballantyne, B

    1977-12-01

    Dibenz(b,f)-1,4-oxazepine (CR), a potent peripheral sensory irritant material, has been shown to have a very low acute lethal and sub-lethal toxicity by intravenous, intraperitoneal, oral, percutaneous and inhalation routes to several species of laboratory mammal. There was no organ-specific pathology. Comparison of the acute toxicity of CR with that of two other peripheral sensory irritants, 1-chloroacetophenone (CN) and 2-chlorobenzyl-lidene malononitrile (CS), shows CR to be significantly less toxic than either of them. Pyrotechnically generated CR smoke was more toxic than pure (thermally generated) aerosols of CR; this was due to the presence of pyrotechnic decomposition products in the atmosphere from the burning of the smoke generating composition. However, the median lethal toxicity of pyrotechnically generated CR smoke was very significantly less than that of either pyrotechnically generated CN or CS smokes. Short-term cumulative toxicity did not occur following multiple oral dosing with CR. The acute toxicology of three ether intermediates encountered in the synthesis of CR from 1-chloro-2-nitrobenzene and sodium phenoxide (2-nitrodiphenyl ether, 2-aminodiphenyl ether and 2-formamidodiphenyl ether) was investigated; all three ethers were found to be less acutely toxic than CR itself.

  3. Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

    PubMed

    Riederer, Anne M; Campleman, Sharan L; Carlson, Robert G; Boyer, Edward W; Manini, Alex F; Wax, Paul M; Brent, Jeffrey A

    2016-01-01

    Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention. PMID:27413997

  4. Lewisite: its chemistry, toxicology, and biological effects.

    PubMed

    Goldman, M; Dacre, J C

    1989-01-01

    routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic. PMID:2692088

  5. Lewisite: its chemistry, toxicology, and biological effects.

    PubMed

    Goldman, M; Dacre, J C

    1989-01-01

    routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic.

  6. Toxicological effects of pyrethroids on non-target aquatic insects.

    PubMed

    Antwi, Frank B; Reddy, Gadi V P

    2015-11-01

    The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments.

  7. Acute Phase Responses to Novel, Investigational Vaccines in Toxicology Studies: The Relationship Between C-Reactive Protein and Other Acute Phase Proteins.

    PubMed

    Green, Martin D

    2015-01-01

    The objective of this study was to determine the effects of investigational vaccine candidates on acute-phase proteins (APPs) as determined in GLP toxicology studies. Sixty-four GLP toxicity studies, which were submitted to the Food and Drug Administration from 2008 to 2012 in support of proposed clinical investigations, were reviewed and entered into a database. These studies employed the intramuscular route of injection and were conducted using New Zealand White rabbits. A retrospective review of these GLP toxicity studies was conducted to evaluate the changes in plasma levels of C-reactive protein (CRP), fibrinogen, and albumin as APPs following the administration of various investigational vaccines. The incidence and intensity of responses associated with acute-phase responses both positive and negative were observed to increase in animals when treated with vaccines containing more potent immunological components such as novel adjuvants that activate Toll-like receptors in the investigational vaccine products. Changes in plasma levels of CRP were prominent among these responses and provided a basis to propose a classification scheme of H, M, L, and N responding groups. These changes in plasma proteins reflect an activation of the acute-phase response and indicate increasing levels of systemic inflammation, which potentially may be correlated with important clinical adverse events.

  8. Male golden hamster in male reproductive toxicology testing: Assessment of protective activity of selenium in acute cadmium intoxication

    SciTech Connect

    Wiodarczyk, B.; Biernacki, B.; Minta, M.; Juszkiewicz, T.; Kozaczynski, W.

    1995-06-01

    The golden hamster has a short history as a laboratory animal. In spite of this, it has been extensively used as a subject for biomedical research. The hamster has also been utilized in toxicological evaluations, especially in teratology studies. Results of these investigations reveal that laboratory hamsters are very sensitive to many chemical compounds, including: drugs, food additives, industrial chemicals, heavy metals, and other environmental contaminants. The animals most frequently used in toxicological investigations are rats and mice. This is also true in male reproductive toxicology. Apparent differences in species sensitivity to chemical compounds suggest a need to examine a new species in this field of toxicology. A good example of chemical specific differences in species sensitivity is the testicular toxicity of 1,2-dibromo-3-chloropropane (DBCP), which was a testicular toxicant in humans and in rats, but it was not effective, even at relatively high dose levels, in the mouse. From our own vast experience in using hamsters in toxicological studies, we decided to use this laboratory animal in male reproductive toxicology screening tests. The purpose of this study was to determine the suitability of golden hamsters as an experimental animal species for male reproductive toxicology testing. To this effect we have chosen selenium and cadmium as test agents as they were well known for their spectacular effect on the male reproductive system. 13 refs., 1 tab.

  9. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    PubMed

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. PMID:27314761

  10. Interrelating the acute and chronic mode of action of inhaled methylenediphenyl diisocyanate (MDI) in rats assisted by computational toxicology.

    PubMed

    Pauluhn, Jürgen

    2011-12-01

    Polymeric methylenediphenyl diisocyanate (MDI) is a high production volume chemical intermediate consisting of monomeric 4,4'-MDI, its 2,2'- and 2,4'-isomers, and higher oligomeric homologues. The toxicity of pMDI has systematically been investigated in previous regulatory and mechanistic studies. One cornerstone of toxicological risk assessment is to understand the critical Mode of Action (MoA) of inhaled MDI aerosol. This paper compares the no-observed-adverse effect levels (NOAELs) in rats from two published whole-body exposure chronic inhalation bioassays with the lung irritation-based point of departures (PODs) from acute and subacute nose-only inhalation studies. Acute irritation was related to elevated concentrations of protein in bronchoalveolar lavage fluid (short-term studies), whilst the chronic events were characterized by histopathology. In the chronic bioassay the exposure duration was either 6 or 18h/day while in all other studies a 6h/day regimens were applied. The major objective of this paper is to analyze the interrelationship of acute pulmonary irritation and the acute-on-chronic manifestations of pulmonary disease following recurrent chronic inhalation exposure. This included considerations on the most critical metrics of exposure with regard to the acute concentration×exposure duration per day (C×T(day)) and the chronic cumulative dose metrics. In summary, this analysis supports the conclusion that the C×T(day) relative to the acute pulmonary irritation threshold is more decisive for the chronic outcome than the concentration per se or the time-adjusted cumulative dose. For MDI aerosols, the acute threshold C×T(day) was remarkably close to the NOAELs of the chronic inhalation studies, independent on their differing exposure mode and regimens. This evidence is supportive of a simple, direct MoA at the site of initial deposition of aerosol. Accordingly, for chemicals reactive to the endogenous nucleophilic agents contained in the lining

  11. Toxicology and cellular effect of manufactured nanomaterials

    DOEpatents

    Chen, Fanqing

    2014-07-22

    The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

  12. Evaluation of nutritional and sub-acute toxicological study of plant based supplement of Achyranthes aspera.

    PubMed

    Fatima, Nudrat; Dar, Nabeela G; Imran, Hina; Sohail, Tehmina; Asghar, Uzma; Yaqeen, Zahra; Syed, Shazia; Jamil, Khalid

    2014-09-01

    The present study was conducted for the nutritional, microbiological and toxicological evaluation of test compound having main ingredient Achyranthes aspera. Nutritional value assessment, microbiological analysis and toxicological studies were conducted according to the standard reported methods which exhibited that A. aspera contains moisture 4.05%, proteins 20.54%, fats 0.903%, ash 20.25%, carbohydrates 54,26% and energy 294 Kcal. Vitamin profile was found to be B(1) 0.27mg/100g, B(2) 0.28mg/100g, B(3) 0.58mg/100g, B(6) 0.27mg/100g and B(9) 39μg/100g. The content of sodium, calcium, magnesium, potassium, chloride and phosphorus was found to be 1119.67, 5385.23, 5446.08, 1343.6, 675880.73 and 1447.5mg/kg respectively and trace metals i.e. iron, copper, zinc, manganese and aluminum were detected as 283.05, 8.062, 48.37, 16.12 and 9.853 mg/kg respectively. The microbiological result indicated that the compound qualifies the international standards of microbial limit and was found free from Salmonella species. The toxicological study was conducted to find safe use of Achyranthes aspera compound in human as a nutritive supplement in blood disorders. The toxicity studies exhibited that the test compound has a good effect on general health as an increase in body weights of animals of test group was noticed as compared to that of control group. Blood parameters before and after the study were monitored which confirms our hypothesis by showing an increase in hemoglobin from 9.133 to 10.96, RBC count from 3.11 to 3.6, WBC count from 5.68 to 5.73 and platelets from 245 to 319. PMID:25176360

  13. Evaluation of nutritional and sub-acute toxicological study of plant based supplement of Achyranthes aspera.

    PubMed

    Fatima, Nudrat; Dar, Nabeela G; Imran, Hina; Sohail, Tehmina; Asghar, Uzma; Yaqeen, Zahra; Syed, Shazia; Jamil, Khalid

    2014-09-01

    The present study was conducted for the nutritional, microbiological and toxicological evaluation of test compound having main ingredient Achyranthes aspera. Nutritional value assessment, microbiological analysis and toxicological studies were conducted according to the standard reported methods which exhibited that A. aspera contains moisture 4.05%, proteins 20.54%, fats 0.903%, ash 20.25%, carbohydrates 54,26% and energy 294 Kcal. Vitamin profile was found to be B(1) 0.27mg/100g, B(2) 0.28mg/100g, B(3) 0.58mg/100g, B(6) 0.27mg/100g and B(9) 39μg/100g. The content of sodium, calcium, magnesium, potassium, chloride and phosphorus was found to be 1119.67, 5385.23, 5446.08, 1343.6, 675880.73 and 1447.5mg/kg respectively and trace metals i.e. iron, copper, zinc, manganese and aluminum were detected as 283.05, 8.062, 48.37, 16.12 and 9.853 mg/kg respectively. The microbiological result indicated that the compound qualifies the international standards of microbial limit and was found free from Salmonella species. The toxicological study was conducted to find safe use of Achyranthes aspera compound in human as a nutritive supplement in blood disorders. The toxicity studies exhibited that the test compound has a good effect on general health as an increase in body weights of animals of test group was noticed as compared to that of control group. Blood parameters before and after the study were monitored which confirms our hypothesis by showing an increase in hemoglobin from 9.133 to 10.96, RBC count from 3.11 to 3.6, WBC count from 5.68 to 5.73 and platelets from 245 to 319.

  14. Toxicological profile for selenium. (Update)

    SciTech Connect

    1996-08-01

    Each profile includes: (1) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (2) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chonic health effects; and (3) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.

  15. Deoxynivalenol: toxicology and potential effects on humans.

    PubMed

    Pestka, James J; Smolinski, Alexa T

    2005-01-01

    Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereal-based foods worldwide. At the molecular level, DON disrupts normal cell function by inhibiting protein synthesis via binding to the ribosome and by activating critical cellular kinases involved in signal transduction related to proliferation, differentiation, and apoptosis. Relative to toxicity, there are marked species differences, with the pig being most sensitive to DON, followed by rodent > dog > cat > poultry > ruminants. The physiologic parameter that is most sensitive to low-level DON exposure is the emetic response, with as little as 0.05 to 0.1 mg/kg body weight (bw) inducing vomiting in swine and dogs. Chinese epidemiological studies suggest that DON may also produce emetic effects in humans. With respect to chronic effects, growth (anorexia and decreased nutritional efficiency), immune function, (enhancement and suppression), and reproduction (reduced litter size) are also adversely affected by DON in animals, whereas incidence of neoplasia is not affected. When hazard evaluations were conducted using existing chronic toxicity data and standard safety factors employed for anthropogenic additives/contaminants in foods, tolerable daily intakes (TDIs) ranging from 1 to 5 microg/kg bw have been generated. Given that critical data gaps still exist regarding the potential health effects of DON, additional research is needed to improve capacity for assessing adverse health effects of this mycotoxin. Critical areas for future DON research include molecular mechanisms underlying toxicity, sensitivity of human cells/tissues relative to other species, emetic effects in primates, epidemiological association with gastroenteritis and chronic disease in humans, and surveillance in cereal crops worldwide.

  16. Toxicological effects of aerial application of monocrotophos.

    PubMed

    Rao, R R; Quadros, F; Mazmudar, R M; Marathe, M R; Gangoli, S D

    1980-01-01

    Aerial application of the insecticide Nuvacron 40% (monocrotophos) had no significant effect on the cholinesterase level of plasma and erythrocytes of cattle, chicken, buffaloes, and human volunteers exposed to the spray. Contamination of canal water with the pesticide was completely eliminated within 24 hr, whereas that in the soil was reduced by 80% in 72 hr. The degradation of insecticide residue in grass was about 90% in seven days and in cotton leaves about 85% for the same period.

  17. Risk assessment and toxicology databases for health effects assessment

    SciTech Connect

    Lu, P.Y.; Wassom, J.S.

    1990-12-31

    Scientific and technological developments bring unprecedented stress to our environment. Society has to predict the results of potential health risks from technologically based actions that may have serious, far-reaching consequences. The potential for error in making such predictions or assessment is great and multiplies with the increasing size and complexity of the problem being studied. Because of this, the availability and use of reliable data is the key to any successful forecasting effort. Scientific research and development generate new data and information. Much of the scientific data being produced daily is stored in computers for subsequent analysis. This situation provides both an invaluable resource and an enormous challenge. With large amounts of government funds being devoted to health and environmental research programs and with maintenance of our living environment at stake, we must make maximum use of the resulting data to forecast and avert catastrophic effects. Along with the readily available. The most efficient means of obtaining the data necessary for assessing the health effects of chemicals is to utilize applications include the toxicology databases and information files developed at ORNL. To make most efficient use of the data/information that has already been prepared, attention and resources should be directed toward projects that meticulously evaluate the available data/information and create specialized peer-reviewed value-added databases. Such projects include the National Library of Medicine`s Hazardous Substances Data Bank, and the U.S. Air Force Installation Restoration Toxicology Guide. These and similar value-added toxicology databases were developed at ORNL and are being maintained and updated. These databases and supporting information files, as well as some data evaluation techniques are discussed in this paper with special focus on how they are used to assess potential health effects of environmental agents. 19 refs., 5 tabs.

  18. Toxicological effects of dietary nickel chloride on intestinal microbiota.

    PubMed

    Wu, Bangyuan; Cui, Hengmin; Peng, Xi; Pan, Kangcheng; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Huang, Jianying

    2014-11-01

    This study was designed to evaluate the toxicological effect of dietary nickel chloride (NiCl2) on the counts of intestinal bacteria and diversity of microorganisms in broilers. Plate counting and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) assays were used. A total of 240 one-day-old avian broilers chicks were divided into four equal groups and kept on corn-soybean basal diet along with supplementation of 0, 300, 600 and 900 mg/kg NiCl2 for 42 days. Samples were taken at 21 and 42 days of age during the experiment. The bacterial count results showed that dietary NiCl2 in the range of 300 to 900 mg/kg decreased the counts of Bifidobacterium spp. and Lactobacillus, increased Escherichia coli (E. coli) and Enterococcus spp. in the ileum and cecum. PCR-DGGE analysis showed that bacterial band numbers, profile similarity, and the Shannon index of the ileum and cecum were all decreased in the 300, 600, and 900 mg/kg groups at 21 and 42 days of age. In conclusion, dietary NiCl2 affected the amount and diversity of intestinal microbiota in the ileum and cecum of broilers. This finding implies that NiCl2 has toxicological effect on the intestinal ecosystem and, possibly functions. PMID:25164205

  19. Green toxicology.

    PubMed

    Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

    2014-01-01

    Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops

  20. Geochemical properties of coal wastes and the toxicological effects on aquatic life. Environmental geology notes

    SciTech Connect

    Roy, W.R.; Krapac, I.G.; Griffin, R.A.; Dickerson, D.R.; Schuller, R.M.

    1984-01-01

    Leachates from solid wastes generated by coal mining, cleaning, and gasification are potentially harmful to the environment. The toxicological effects of leachates on aquatic organisms have not been adequately assessed. In this investigation, samples of seven coal-related wastes were charcterized chemically and mineralogically. Laboratory extracts of each sample, obtained by a variety of extraction methods, were used in both acute and chronic bioassay. A coal-slurry sample (coarse fraction) and two samples of coal-cleaning refuse were chemically and mineralogically similar; they generated acidic water-waste systems, both in the laboratory and in the field. Two mine-spoil samples, essentially shale, tended to generate water-waste systems that were neutral in pH; consequently, they released lower quantities of potential pollutants than the acidic wastes. Each extract was tested for acute toxicity with four species of fresh-water aquatic organisms; the green sunfish (Lepomis cyanellus), the fathead minnow, (Pimephales promelas), a crustacean (Daphia magna), and a snail (Physa anatina). The extracts of the two mine spoil samples and of the gasification residue were not toxic to any of the organisms; whereas the extracts from the acidic refuse and slurry samples were acutely toxic to all the organisms.

  1. Developmental Toxicology##

    EPA Science Inventory

    Developmental toxicology encompasses the study of developmental exposures, pharmacokinetics, mechanisms, pathogenesis, and outcomes potentially leading to adverse health effects. Manifestations of developmental toxicity include structural malformations, growth retardation, functi...

  2. 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.

  3. Acute, subchronic, and developmental toxicological properties of lubricating oil base stocks.

    PubMed

    Dalbey, Walden E; McKee, Richard H; Goyak, Katy Olsavsky; Biles, Robert W; Murray, Jay; White, Russell

    2014-01-01

    Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.

  4. Pharmacological and Toxicological Effects of Lithium in Zebrafish

    PubMed Central

    2014-01-01

    Lithium is the paradigmatic treatment for bipolar disorder and has been widely used as a mood stabilizer due to its ability to reduce manic and depressive episodes, efficiency in long-term mood stabilization, and effectiveness in reducing suicide risks. Despite many decades of clinical use, the molecular targets of lithium are not completely understood. However, they are credited at least partially to glycogen synthase kinase 3 (GSK3) inhibition, mimicking and exacerbating Wnt signaling pathway activation. There has been a great effort to characterize lithium cellular and system actions, aiming to improve treatment effectiveness and reduce side effects. There is also a growing concern about lithium’s impact as an environmental contaminant and its effects on development. In this scenario, zebrafish is a helpful model organism to gather more information on lithium’s effects in different systems and developmental stages. The rapid external development, initial transparency, capacity to easily absorb substances, and little space required for maintenance and experimentation, among other advantages, make zebrafish a suitable model. In addition, zebrafish has been established as an effective model organism in behavioral and neuropharmacological studies, reacting to a wide range of psychoactive drugs, including lithium. So far only a limited number of studies evaluated the toxicological impact of lithium on zebrafish development and demonstrated morphological, physiological, and behavioral effects that may be informative regarding human findings. Further studies dedicated to characterize and evaluate the underlying mechanisms of the toxic effects and the potential impact of exposure on developing and adult individuals are necessary to establish safe clinical management guidelines for women with bipolar disorder of childbearing age and safety disposal guidelines for pharmaceutical neuroactive compounds. PMID:24798681

  5. Pharmacological and toxicological effects of lithium in zebrafish.

    PubMed

    Siebel, Anna M; Vianna, Monica R; Bonan, Carla D

    2014-06-18

    Lithium is the paradigmatic treatment for bipolar disorder and has been widely used as a mood stabilizer due to its ability to reduce manic and depressive episodes, efficiency in long-term mood stabilization, and effectiveness in reducing suicide risks. Despite many decades of clinical use, the molecular targets of lithium are not completely understood. However, they are credited at least partially to glycogen synthase kinase 3 (GSK3) inhibition, mimicking and exacerbating Wnt signaling pathway activation. There has been a great effort to characterize lithium cellular and system actions, aiming to improve treatment effectiveness and reduce side effects. There is also a growing concern about lithium's impact as an environmental contaminant and its effects on development. In this scenario, zebrafish is a helpful model organism to gather more information on lithium's effects in different systems and developmental stages. The rapid external development, initial transparency, capacity to easily absorb substances, and little space required for maintenance and experimentation, among other advantages, make zebrafish a suitable model. In addition, zebrafish has been established as an effective model organism in behavioral and neuropharmacological studies, reacting to a wide range of psychoactive drugs, including lithium. So far only a limited number of studies evaluated the toxicological impact of lithium on zebrafish development and demonstrated morphological, physiological, and behavioral effects that may be informative regarding human findings. Further studies dedicated to characterize and evaluate the underlying mechanisms of the toxic effects and the potential impact of exposure on developing and adult individuals are necessary to establish safe clinical management guidelines for women with bipolar disorder of childbearing age and safety disposal guidelines for pharmaceutical neuroactive compounds. PMID:24798681

  6. The toxicological effects of heavy fuel oil category substances.

    PubMed

    McKee, Richard H; Reitman, Fred; Schreiner, Ceinwen; White, Russell; Charlap, Jeffrey H; O'Neill, Thomas P; Goyak, Katy Olsavsky

    2014-01-01

    Heavy fuel oil (HFO) category substances are used to manufacture HFO, a product used in industrial boilers and marine diesel engines. Commercial HFOs and blending stream components are substances of complex and variable composition, composed of C20 to >C50 hydrocarbons, although lower molecular weight material may be added to reduce viscosity and improve flow characteristics. An HFO blending stream (catalytically cracked clarified oil [CCCO]) was tested for target organ and developmental toxicity in rats following repeated dermal administration at doses of 5, 25, or 50 mg/kg/d. In the repeated dose study, there was evidence of increased liver weights, reduced thymus weights, and reductions in hematological parameters with an overall no observed adverse effect level (NOAEL) of 5 mg/kg/d. In the developmental toxicity test, there were significant reductions in fetal survival, significant increases in resorption frequency, and significantly reduced fetal weights with an overall NOAEL of 5 mg/kg/d. These target organ and developmental effects are associated with the types and levels of aromatic constituents in these substances. Among HFO blending streams, CCCOs have the highest levels of aromatics and, because they produce the characteristic toxicological effects at the lowest levels, are considered as "reasonable worst-case examples" for this group of substances. Other HFO category members with lower levels of aromatics produce similar effects but have higher NOAELs. The potential for target organ and developmental effects of other HFO category members can be predicted from information on the types and levels of the aromatic constituents present in these substances.

  7. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    EPA Science Inventory

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  8. Genetic and acute toxicological evaluation of an algal oil containing eicosapentaenoic acid (EPA) and palmitoleic acid.

    PubMed

    Collins, M L; Lynch, B; Barfield, W; Bull, A; Ryan, A S; Astwood, J D

    2014-10-01

    Algal strains of Nannochloropsis sp. were developed, optimized, cultivated and harvested to produce a unique composition of algal oil ethyl esters (Algal-EE) that are naturally high in eicosapentaenoic acid (EPA, 23-30%) and palmitoleic acid (20-25%), and contain no docosahexaenoic acid (DHA). Algal-EE was evaluated for mutagenic activity (Ames bacterial reverse mutation, in vitro mammalian chromosome aberration, in vivo micronucleus test) and for acute oral toxicity in Sprague-Dawley rats. In the acute toxicity study, rats received a single oral gavaged dose of Algal-EE (2000 mg/kg body weight). Clinical observations were made for 14 days before sacrifice on Day 15. Macroscopic evaluation involved the examination of all organs in the cranial, thoracic, and abdominal cavities. Algal-EE showed no evidence of mutagenicity, did not produce an increase in the frequency of structural chromosome aberrations, and did not cause an increase in the induction of micronucleated polychromatic erythrocytes. There were no macroscopic abnormalities. Algal-EE up to 2000 mg/kg body weight did not affect body weight, organ appearance or produce any toxic-related signs of morbidity. The acute median lethal dose (LD50) of Algal-EE was >2000 mg/kg body weight. Based on these assays, Algal-EE does not appear to have any genetic or acute oral toxicity. PMID:25057807

  9. The acute, developmental, genetic and inhalation toxicology of 2,3,3,3-tetrafluoropropene (HFO-1234yf).

    PubMed

    Tveit, Ann; Rusch, George M; Muijser, Hans; Tegelenbosch-Schouten, Mariska-M

    2013-10-01

    2,3,3,3-Tetrafluoropropene (HFO-1234yf) is being developed as a refrigerant because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons, which is intended to replace with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 101,850 or 405,800 ppm, respectively. Additionally, there was no mortality or clinical signs of toxicity when rabbits were exposed to 100,000 ppm for 1 hour. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin in dogs. Rats were exposed to HFO-1234yf at levels of 5000, 20,000 and 50,000 ppm 6 hours/day 5 days/week for 2 weeks and at levels of 5000, 15,000 and 50,000 ppm for 4 weeks and for 90 days. No treatment-related adverse effects were noted in these studies. HFO-1234yf was not genotoxic in a mouse and a rat micronucleus assay, and unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. HFO-1234yf was mutagenic to Salmonella typhimurium TA 100 and Escherichia coli (WP2 uvrA) at concentrations of 20% and higher in the presence of metabolic activation only. There were no biologically significant effects in a rat developmental toxicity study with exposures up to 50,000 ppm.

  10. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day.

  11. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day. PMID:23353547

  12. TOXICOLOGICAL EFFECTS OF PARTICULATE MATTER DERIVED FROM THE DESTRUCTION OF THE WORLD TRADE CENTER

    EPA Science Inventory

    May 15, 2002
    Abstract submitted by Stephen H. Gavett for American Association for Aerosol Research (AAAR) annual meeting October 7-11, 2002 in Charlotte, NC.

    TOXICOLOGICAL EFFECTS OF PARTICULATE MATTER DERIVED FROM THE DESTRUCTION OF THE WORLD TRADE CENTER
    Stephen H ...

  13. Toxicological profile for methyl t-butyl ether

    SciTech Connect

    1996-08-01

    Each profile includes: (1) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (2) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chonic health effects; and (3) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans.

  14. Genetic toxicology: web resources.

    PubMed

    Young, Robert R

    2002-04-25

    Genetic toxicology is the scientific discipline dealing with the effects of chemical, physical and biological agents on the heredity of living organisms. The Internet offers a wide range of online digital resources for the field of Genetic Toxicology. The history of genetic toxicology and electronic data collections are reviewed. Web-based resources at US National Library of Medicine (NLM), including MEDLINE, PUBMED, Gateway, Entrez, and TOXNET, are discussed. Search strategies and Medical Subject Headings (MeSH) are reviewed in the context of genetic toxicology. The TOXNET group of databases are discussed with emphasis on those databases with genetic toxicology content including GENE-TOX, TOXLINE, Hazardous Substances Data Bank, Integrated Risk Information System, and Chemical Carcinogenesis Research Information System. Location of chemical information including chemical structure and linkage to health and regulatory information using CHEMIDPLUS at NLM and other databases is reviewed. Various government agencies have active genetic toxicology research programs or use genetic toxicology data to assist fulfilling the agency's mission. Online resources at the US Food and Drug Administration (FDA), the US Environmental Protection Agency (EPA), the National Institutes of Environmental Health Sciences, and the National Toxicology Program (NTP) are outlined. Much of the genetic toxicology for pharmaceuticals, industrial chemicals and pesticides that is performed in the world is regulatory-driven. Regulatory web resources are presented for the laws mandating testing, guidelines on study design, Good Laboratory Practice (GLP) regulations, and requirements for electronic data collection and reporting. The Internet provides a range of other supporting resources to the field of genetic toxicology. The web links for key professional societies and journals in genetic toxicology are listed. Distance education, educational media resources, and job placement services are also

  15. Analytical toxicology.

    PubMed

    Flanagan, R J; Widdop, B; Ramsey, J D; Loveland, M

    1988-09-01

    1. Major advances in analytical toxicology followed the introduction of spectroscopic and chromatographic techniques in the 1940s and early 1950s and thin layer chromatography remains important together with some spectrophotometric and other tests. However, gas- and high performance-liquid chromatography together with a variety of immunoassay techniques are now widely used. 2. The scope and complexity of forensic and clinical toxicology continues to increase, although the compounds for which emergency analyses are needed to guide therapy are few. Exclusion of the presence of hypnotic drugs can be important in suspected 'brain death' cases. 3. Screening for drugs of abuse has assumed greater importance not only for the management of the habituated patient, but also in 'pre-employment' and 'employment' screening. The detection of illicit drug administration in sport is also an area of increasing importance. 4. In industrial toxicology, the range of compounds for which blood or urine measurements (so called 'biological monitoring') can indicate the degree of exposure is increasing. The monitoring of environmental contaminants (lead, chlorinated pesticides) in biological samples has also proved valuable. 5. In the near future a consensus as to the units of measurement to be used is urgently required and more emphasis will be placed on interpretation, especially as regards possible behavioural effects of drugs or other poisons. Despite many advances in analytical techniques there remains a need for reliable, simple tests to detect poisons for use in smaller hospital and other laboratories.

  16. Behavioral toxicology

    SciTech Connect

    Needleman, H.L.

    1995-09-01

    The new fields of behavioral toxicology and behavioral teratology investigate the outcome of specific toxic exposures in humans and animals on learning, memory, and behavioral characteristics. Three important classes of behavioral neurotoxicants are metals, solvents, and pesticides. The clearest data on the deleterious effects of prenatal exposure to toxicants comes from the study of two metals, lead and mercury, and form epidemiological investigations of the effects of alcohol taken during pregnancy. Less complete data are available for two other groups of agents, solvents, and pesticides. What we do know about their effects on the fetal brain is convincing enough to make us demand caution in their distribution. 15 refs.

  17. The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

    NASA Astrophysics Data System (ADS)

    Yan, Jun; Lin, Bencheng; Hu, Chuanlu; Zhang, Huashan; Lin, Zhiqing; Xi, Zhuge

    2014-08-01

    Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture.

  18. [Eco-toxicological effect of metal-based nanoparticles on plants: Research progress].

    PubMed

    Zhang, Hai; Peng, Cheng; Yang, Jian-Jun; Shi, Ji-yan

    2013-03-01

    The rapid development of nanotechnology and the potential environmental risk of wide application of artificial nanoparticles (NPs) have raised considerable concerns. Metal-based nanoparticles (MB NPs) have dual-toxicity of metal and NPs, and thus, their bio-toxicity and ecological risk are the hotspots in the studies of nanotoxicology. Plant, as a main component of ecosystem, is a potential pathway for NPs bioaccumulation and entering into food chain. This paper discussed the MB NPs absorption, translocation, and accumulation by plants, and summarized the eco-toxicological effect of MB NPs on plants and related mechanisms. The factors affecting the phytotoxicity of MB NPs were approached, and the research progress on the eco-toxicological effect of MB NPs on plants, especially on food crops, was reviewed. Also, the existing problems in present MB NPs phytotoxicity studies were analyzed, and the future research directions were proposed.

  19. Biochemical and toxicological evidence of neurological effects of pesticides: the example of Parkinson's disease.

    PubMed

    Moretto, A; Colosio, C

    2011-08-01

    Parkinson's disease (PD) is frequently reported to be associated with pesticide exposure but the issue has not yet been solved because the data are inconsistent and the studies suffer from several biases and limitations. The aim of this article is to summarise available biochemical and toxicological data on some pesticides, particularly on paraquat, that might help in the evaluation of epidemiological data. The nigrostriatal system appears to be particularly sensitive to oxidative damage caused by different mechanisms and agents, thus supporting the epidemiological evidence that Parkinson's disease is in fact an environmental disease. In available experimental studies, animals have been treated with a high single or a few doses of pesticide, and have been followed up for a few days or weeks after treatment. Moreover, experimental data indicate additive/synergistic effects of different pesticides that act on different targets within the dopaminergic system. In these conditions and to a different extent, pesticides such as paraquat, maneb and other dithiocarbamates, pyrethroids, rotenone, and dieldrin cause neurotoxic effects that may suggest a possible role in the development of a PD-like syndrome in animals. Although, all the characteristics of PD cannot be reproduced by any single chemical, these data can be of help for understanding the role of pesticide exposure in human PD development. On the other hand farmers are exposed for days or weeks during several years to much lower doses than those used in experimental studies. Therefore, a firm conclusion on the role of pesticide exposure on the increased risk of developing PD cannot be drawn. However, it is suggested that close follow up of survivors of acute poisonings by these pesticides, or identification in epidemiological studies of such subjects or of those reporting episodes of accidentally high exposure will certainly provide information useful for the understanding of the relevance of actual human exposure

  20. An argument for the chicken embryo as a model for the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs)

    SciTech Connect

    Henshel, D.S.

    1996-12-31

    This article will present the argument that the chicken embryo is especially appropriate as an animal model for studying the mechanism of the developmental toxicological effects of the polyhalogenated aromatic hydrocarbons (PHAHs). The PHAHs are a group of toxicologically related compounds including, in part, the polychlorinated dibenzodioxins, dibenzofurans and biphenyls. The chicken (Gallus gallus) embryo is relatively sensitive to the toxicological effects of the PHAHs being approximately two orders of magnitude more sensitive than the mature bird. The chicken embryo has been used to demonstrate general toxicological teratogeneicity, hepatotoxicity and neurotoxicity. Many of these effects, or analogous effects, have also been observed in mammals and fish. Thus, most animals appear to respond to the PHAHs with a similar toxicological profile, indicating that many of the biomarkers used for the PHAHs are valid across a number of species, including the chicken. Furthermore, the chicken embryo is relatively inexpensive to use for toxicity testing. In addition, all effects detected are due to direct effects on the embryo and are not complicated by maternal interactions. In short, for sensitivity, ease of use, cost and applicability of results to other animals, the chicken embryo is an excellent animal model for evaluation of the mechanism underlying the developmental toxicological effects of the PHAHs.

  1. Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors.

    PubMed

    Cho, Chul-Woong; Stolte, Stefan; Yun, Yeoung-Sang

    2016-01-01

    The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R(2) of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R(2) of 0.901 and SE of 0.426 log unit. PMID:27624396

  2. Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors.

    PubMed

    Cho, Chul-Woong; Stolte, Stefan; Yun, Yeoung-Sang

    2016-09-14

    The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R(2) of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R(2) of 0.901 and SE of 0.426 log unit.

  3. Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors

    NASA Astrophysics Data System (ADS)

    Cho, Chul-Woong; Stolte, Stefan; Yun, Yeoung-Sang

    2016-09-01

    The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R2 of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R2 of 0.901 and SE of 0.426 log unit.

  4. Comprehensive approach for predicting toxicological effects of ionic liquids on several biological systems using unified descriptors

    PubMed Central

    Cho, Chul-Woong; Stolte, Stefan; Yun, Yeoung-Sang

    2016-01-01

    The challenge and opportunity for design of environmentally-benign ionic liquids (ILs) would start from prediction of their toxicological effects on several endpoints solely based on the structural formulas. Especially, a comprehensive yet simple equation able to predict several biological responses to IL toxicity is of much advantage. Therefore, based on 50 toxicity testing systems on ILs a comprehensively approachable prediction method was developed. For the modelling, approximately 1600 toxicity values measured by several biological systems and an amended linear free energy relationship (LFER) model were used. Since the toxicological activities of an IL could be differently described according to sensitivity of toxicity testing systems, the sensitivity of each of toxicity testing systems was also estimated in the modelling. By statistical analysis with the calculated descriptors, a LFER model was built. Also the sensitivity value of each system on the basis of the comprehensively approachable model was numerically estimated. In results, it was observed that the combination of single model and sensitivity terms was able to predict each of 50 toxicological effects of ILs with R2 of 0.593~0.978, and SE of 0.098~0.699 log unit, and the total data set with R2 of 0.901 and SE of 0.426 log unit. PMID:27624396

  5. Quantification of toxicological effects for dichloromethane. Final report

    SciTech Connect

    Not Available

    1992-01-01

    The document discusses the quantification of non-carcinogenic effects and carcinogenic effects for dichloromethane. The evaluation of non-carcinogenic effects includes a study of short and long term effects in animals and humans, as well as the development of the one-day, ten-day, and long term health advisories. The evaluation of carcinogenic effects includes a categorization of carcinogenic potential and risks estimates. There is a brief discussion on existing guidelines or standards and special considerations such as high risk groups.

  6. New insights into the pharmacological and toxicological effects of thalidomide.

    PubMed

    Meierhofer, Christian; Wiedermann, Christian J

    2003-01-01

    The molecular activity of thalidomide comprises a wide range of mechanisms. Alteration of cytokine synthesis and release may be as important as changes in lymphocyte trafficking and leukocyte migration. Since endothelial cells play an important role in leukocyte extravasation and maintenance of inflammatory processes in the affected tissue, thalidomide-induced alterations of cellular adhesion molecules, and consequently changes of interaction of leukocytes with the endothelial cell layer, will result in modulation of the response in inflammation and immunity. Thalidomide mainly reduces tumor necrosis factor (TNF)-alpha production by macrophages, and its TNF alpha antagonist properties explain the beneficial effects in several TNF alpha-associated complications of severe diseases. Pathophysiologically relevant alterations most likely include gene regulatory effects, with interference in growth factor-dependent pathways known to be involved in teratogenesis, and effects on the transcriptional control of the inflammatory response via nuclear factor (NF)-kappa B. The effects of thalidomide, its enantiomers and analogs, on a broad range of diseases, and their differential pharmacokinetic and pharmacodynamic properties, give the scope for ongoing investigations in the search for analogs with better selectivity but without thalidomide-related side effects and teratogenicity.

  7. Characterization of Soy Biodiesel Exhaust and Toxicological Effects in Mice

    EPA Science Inventory

    Although biofuel use across the world is increasing, very little is known about possible health effects resulting from biofuel exhaust (BE) from this relatively new source of transportation fuel. The U.S. EPA has instigated an in vivo screening approach in rodents to examine whet...

  8. What are the toxicological effects of mercury in Arctic biota?

    PubMed

    Dietz, Rune; Sonne, Christian; Basu, Niladri; Braune, Birgit; O'Hara, Todd; Letcher, Robert J; Scheuhammer, Tony; Andersen, Magnus; Andreasen, Claus; Andriashek, Dennis; Asmund, Gert; Aubail, Aurore; Baagøe, Hans; Born, Erik W; Chan, Hing M; Derocher, Andrew E; Grandjean, Philippe; Knott, Katrina; Kirkegaard, Maja; Krey, Anke; Lunn, Nick; Messier, Francoise; Obbard, Marty; Olsen, Morten T; Ostertag, Sonja; Peacock, Elizabeth; Renzoni, Aristeo; Rigét, Frank F; Skaare, Janneche Utne; Stern, Gary; Stirling, Ian; Taylor, Mitch; Wiig, Øystein; Wilson, Simon; Aars, Jon

    2013-01-15

    This review critically evaluates the available mercury (Hg) data in Arctic marine biota and the Inuit population against toxicity threshold values. In particular marine top predators exhibit concentrations of mercury in their tissues and organs that are believed to exceed thresholds for biological effects. Species whose concentrations exceed threshold values include the polar bears (Ursus maritimus), beluga whale (Delphinapterus leucas), pilot whale (Globicephala melas), hooded seal (Cystophora cristata), a few seabird species, and landlocked Arctic char (Salvelinus alpinus). Toothed whales appear to be one of the most vulnerable groups, with high concentrations of mercury recorded in brain tissue with associated signs of neurochemical effects. Evidence of increasing concentrations in mercury in some biota in Arctic Canada and Greenland is therefore a concern with respect to ecosystem health. PMID:23231888

  9. An appraisal of the pharmacological and toxicological effects of a single oral administration of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.

    PubMed

    De Souza, I; Kelly, J P; Harkin, A J; Leonard, B E

    1997-05-01

    This study examined some acute pharmacological and toxicological effects of 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy") over a range of doses (20, 40, 80, 160 and 320 mg/kg orally) in adult female rats. Deaths were observed from the 40 mg/kg MDMA group onwards. Reductions in body weight change, food and water intake were found in the 80 mg/kg group, whilst food intake alone was reduced in the 20 and 40 mg/kg groups. Significant hyperthermic responses were found over the first 8 hr following MDMA administration which were dose-related. A significant hyperactivity of approximately 9 hr duration was observed in the 20 mg/kg and 40 mg/kg groups, whereas there was evidence of a serotonin syndrome in the higher dosage groups. Thus, acute oral administration of MDMA results in a variety of measurable responses. The cause of death in this study is probably a combination of serotonin syndrome and hyperthermia.

  10. Glucose Effect in the Acute Porphyrias

    MedlinePlus

    ... You are here Home Diet and Nutrition The glucose effect in acute porphyrias The disorders Acute Intermittent ... are treated initially with the administration of carbohydrate/glucose. This therapy has its basis in the ability ...

  11. Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

    PubMed Central

    Douglas, G R; Hugenholtz, A P; Blakey, D H

    1986-01-01

    The effects of DEHP on sperm morphology and on peripheral blood micronuclei were studied for 12 weeks following five subacute IP injections of DEHP at 1/6, 1/12, and 1/60 of the LD50 per day. Sperm morphology was examined in both adult mice and rats, while peripheral blood micronuclei were scored in mice up to 4 weeks after treatment. In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks. Numbers of morphologically abnormal sperm did not differ from controls in the 12 weeks following treatment. In addition, DEHP did not increase the numbers of peripheral blood micronuclei. Studies in the rat indicated that exposure to doses of 1/6 and 1/12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls. Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment. In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells. Although DEHP is known to cause testicular atrophy in rats and to a lesser extent in mice, it did not cause an increase in abnormal sperm in either species. Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line. PMID:3709450

  12. Toxic effect onset and evaluations of medicinal drugs--horizon for Darwinian toxicological thought.

    PubMed

    Horii, Ikuo

    2010-08-01

    The theory of Darwinian Medicine linked to an extension of Darwin's evolutionary theory is based on the approach from the aspect of "why we become ill?".This theory enables us to understand the relationship between humans and diseases by thinking from evolutional perspective, shows an important help for preventive medicine, and is meaningful to consider the future human healthcare. Toxicology has been defined as a research of adverse effect of xenobiotic substances backed up by diverse-sciences. Toxic effects are basically responses to xenobiotic substances, and expressed as triggering or additional accelerating adverse effects toward abnormal condition. Toxic effects, biological adverse responses, are interpreted as protective responses of living body, and the adverse effects caused by drugs are also considered to be protective responses. This logic can be translated as "Darwinian Toxicology" corresponding to "Darwinian Medicine", replying to "why we get into toxic condition by xenobiotics exposure". This paper refers to the meaning of toxic effects based on mechanisms underlying and comprehensive drug safety evaluation from Darwinian Medicine perspectives.

  13. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    PubMed

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

  14. Toxicology of brotizolam

    PubMed Central

    Hewett, C.; Kreuzer, H.; Köllmer, H.; Niggeschulze, A.; Stötzer, H.

    1983-01-01

    1 Acute studies. Following oral or intraperitoneal administration, toxicity was very low (LD50 in rodents > 10,000 and > 900 mg/kg, respectively). 2 Subacute and chronic studies in rodents. Signs of toxicity were seen only at doses of 400 mg/kg or more. Histopathological changes were found only in the 78-week study. 3 Subacute studies in dogs (intravenous) and primates (oral). In dogs, doses of 0.1 and 0.3 mg/kg produced ataxia, salivation, and diarrhoea. In monkeys doses of 7 mg/kg or higher produced ataxia, increased appetite, hyperreflexive muscular spasms, increase in liver weight, and lipid depletion of the adrenal cortex. 4 Reproductive studies in the rat and rabbit. Repeated doses of up to 30 mg/kg were not associated with any disturbance in fertility; nor were any embryotoxic or teratogenic effects observed. When dams were treated with 400 mg/kg, litter mortality was markedly increased. 5 Mutagenicity studies. The four different tests performed gave no indication of any mutagenic effect. 6 Local tolerance tests in the rabbit. Brotizolam was well tolerated when administered intramuscularly, intra-arterially, or intravenously. 7 Carcinogenicity studies in rodents. The mouse study showed no evidence of a tumourigenic effect. The rat study is still being evaluated. 8 The toxicological studies demonstrate that brotizolam has an unusually wide therapeutic range. Findings of toxicological significance, most of which were reversible, were first recorded at doses of 7-10 mg/kg, i.e. at more than 100-times the intended human therapeutic dose. PMID:6686462

  15. The acute, genetic, developmental and inhalation toxicology of trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)).

    PubMed

    Tveit, Ann; Rusch, George M; Muijser, Hans; van den Hoven, Mabel J W; Hoffman, Gary M

    2014-01-01

    Trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)) is being developed as a foam blowing agent, refrigerant and solvent because it has a very low global warming potential (<10), as contrasted to the hydrofluorocarbons (>500). The toxicology profile is described. The acute 4-hour 50% lethal concentration value in rats receiving HCFO-1233zd(E) was 120 000 ppm. The no observed effect level (NOEL) in cardiac sensitization studies in dogs was 25 000 ppm. In a 2-week range-finding study, rats were exposed to HCFO-1233zd(E) at levels of 0, 2000, 7500 and 20 000 ppm 6 hours/day for 5 days/week. Histopathological changes in the heart described as multifocal mononuclear infiltrates were observed in males (mid- and high-exposure group) and females (high-exposure group), suggesting this organ was the target for HCFO-1233zd(E) toxicity. In a 4-week study, rats were exposed to 0, 2000, 4500, 7500 and 10 000 ppm. The only finding was an increase in potassium (mid- and high-exposure males). No increase was observed after a 2-week recovery period, nor in a subsequent 13-week toxicity study. In a 13-week study, rats were exposed to 4000, 10 000 and 15 000 ppm 6 hours/day for 5 days/week. Findings consisted of multifocal mononuclear cell infiltrates in the heart with a NOEL/lowest observed adverse effect level of 4000 ppm. No genetic toxicity was observed in a battery of genetic toxicity studies. In a rat prenatal developmental toxicity study, dilated bladders were observed in the high-exposure group fetuses (15 000 ppm), a finding of unclear significance. HCFO-1233zd(E) was not a developmental toxin in rabbits, even at exposure levels up to 15 000 ppm. PMID:23869688

  16. The acute, genetic, developmental and inhalation toxicology of trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)).

    PubMed

    Tveit, Ann; Rusch, George M; Muijser, Hans; van den Hoven, Mabel J W; Hoffman, Gary M

    2014-01-01

    Trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)) is being developed as a foam blowing agent, refrigerant and solvent because it has a very low global warming potential (<10), as contrasted to the hydrofluorocarbons (>500). The toxicology profile is described. The acute 4-hour 50% lethal concentration value in rats receiving HCFO-1233zd(E) was 120 000 ppm. The no observed effect level (NOEL) in cardiac sensitization studies in dogs was 25 000 ppm. In a 2-week range-finding study, rats were exposed to HCFO-1233zd(E) at levels of 0, 2000, 7500 and 20 000 ppm 6 hours/day for 5 days/week. Histopathological changes in the heart described as multifocal mononuclear infiltrates were observed in males (mid- and high-exposure group) and females (high-exposure group), suggesting this organ was the target for HCFO-1233zd(E) toxicity. In a 4-week study, rats were exposed to 0, 2000, 4500, 7500 and 10 000 ppm. The only finding was an increase in potassium (mid- and high-exposure males). No increase was observed after a 2-week recovery period, nor in a subsequent 13-week toxicity study. In a 13-week study, rats were exposed to 4000, 10 000 and 15 000 ppm 6 hours/day for 5 days/week. Findings consisted of multifocal mononuclear cell infiltrates in the heart with a NOEL/lowest observed adverse effect level of 4000 ppm. No genetic toxicity was observed in a battery of genetic toxicity studies. In a rat prenatal developmental toxicity study, dilated bladders were observed in the high-exposure group fetuses (15 000 ppm), a finding of unclear significance. HCFO-1233zd(E) was not a developmental toxin in rabbits, even at exposure levels up to 15 000 ppm.

  17. Space Toxicology

    NASA Technical Reports Server (NTRS)

    James, John T.

    2011-01-01

    Safe breathing air for space faring crews is essential whether they are inside an Extravehicular Mobility Suit (EMU), a small capsule such as Soyuz, or the expansive International Space Station (ISS). Sources of air pollution can include entry of propellants, excess offgassing from polymeric materials, leakage of systems compounds, escape of payload compounds, over-use of utility compounds, microbial metabolism, and human metabolism. The toxicological risk posed by a compound is comprised of the probability of escaping to cause air pollution and the magnitude of adverse effects on human health if escape occurs. The risk from highly toxic compounds is controlled by requiring multiple levels of containment to greatly reduce the probability of escape; whereas compounds that are virtually non-toxic may require little or no containment. The potential for toxicity is determined by the inherent toxicity of the compound and the amount that could potentially escape into the breathing air.

  18. Toxicological effects of acrylamide on the reproductive system of weaning male rats.

    PubMed

    Ma, Yuxin; Shi, Jing; Zheng, Meige; Liu, Jing; Tian, Sumin; He, Xinhong; Zhang, Dexing; Li, Guoying; Zhu, Jiayong

    2011-08-01

    It has been reported that acrylamide can be detected in starchy food treated by high temperature (120 °C). People could be exposed to acrylamide in factory, laboratory, or even in daily life via diet and drinking water. Recently, the toxicity of acrylamide receives more attention. In addition to the neurotoxicity in humans, other toxic effects of acrylamide are worth further investigation. In this study, we investigated whether acrylamide affected the male reproductive system using high-performance liquid chromatography. In this study, the reproductive toxicity of acrylamide was observed in 3-week-old weaning male Sprague-Dawley rats treated with acrylamide at various doses (0, 5, 15 or 30 mg/kg/day). The results showed that food availability and reproductive organ indexes of the weaning male rats decreased. Levels of follicle-stimulating hormone and testosterone in serum increased while luteinizing hormone in serum decreased. The histopathological lesions and abnormal sperms presented in weaning rats after acrylamide treatment. The results suggested that there is a toxicological effect of acrylamide on the reproductive system of weaning male rats. Based on the findings above, we suggested that more attention should be paid to the toxicological study of acrylamide on weaning male rats or human beings, rather than just on adult male animals.

  19. Eco-toxicological effects of the avermectin family with a focus on abamectin and ivermectin.

    PubMed

    Bai, Shahla Hosseini; Ogbourne, Steven

    2016-07-01

    Avermectin family members are categorised as highly effective but toxic natural products that are used as pharmaceuticals in both humans and animals and for crop protection. Abamectin and ivermectin are the two most commonly used compounds from this family with abamectin the only compound to be used for both crop protection and pharmaceutical purposes. Avermectins are produced by the soil dwelling actinomycetes Streptomyces avermitilis and despite having complex chemical structures, they are manufactured via synthesis in large scales for commercial use. Although the extent of the eco-toxicological effects of avermectins is not well documented, reports of eco-toxicity exist. Avermectins have short half-lives and their residues can be eliminated through different food processing methods. However, avermectins can persist in water, sediment, soil and food products and therefore management practices that reduce the potential risks associated with eco-toxicity of these highly toxic compounds need to be further developed. This manuscript provides a critical review of the eco-toxicological risks and the potential for food contamination associated with avermectin use. PMID:27058912

  20. Eco-toxicological effects of the avermectin family with a focus on abamectin and ivermectin.

    PubMed

    Bai, Shahla Hosseini; Ogbourne, Steven

    2016-07-01

    Avermectin family members are categorised as highly effective but toxic natural products that are used as pharmaceuticals in both humans and animals and for crop protection. Abamectin and ivermectin are the two most commonly used compounds from this family with abamectin the only compound to be used for both crop protection and pharmaceutical purposes. Avermectins are produced by the soil dwelling actinomycetes Streptomyces avermitilis and despite having complex chemical structures, they are manufactured via synthesis in large scales for commercial use. Although the extent of the eco-toxicological effects of avermectins is not well documented, reports of eco-toxicity exist. Avermectins have short half-lives and their residues can be eliminated through different food processing methods. However, avermectins can persist in water, sediment, soil and food products and therefore management practices that reduce the potential risks associated with eco-toxicity of these highly toxic compounds need to be further developed. This manuscript provides a critical review of the eco-toxicological risks and the potential for food contamination associated with avermectin use.

  1. Dispersant use as a response to oil spills: toxicological effects on fish cardiac performance.

    PubMed

    Milinkovitch, Thomas; Thomas-Guyon, Hélène; Lefrançois, Christel; Imbert, Nathalie

    2013-04-01

    Dispersant use is a controversial technique used to respond to oil spills in nearshore areas. In order to assess the toxicity of this technique, this study evaluated the cardiac toxicological effects on juvenile golden grey mullets Liza aurata exposed for 48 h to either dispersant alone, chemically dispersed oil, mechanically dispersed oil, the water-soluble fraction of oil or a control condition. Following exposure, the positive inotropic effects of adrenaline were assessed in order to evaluate a potential impairment on the cardiac performance. The results revealed an impairment of the positive inotropic effects of adrenaline for all the contaminants (single dispersant, dispersed and undispersed oil, water-soluble fraction of oil). This suggests that: (1) cardiac performance is a valuable parameter to study the physiopathological effects of dispersed oil; (2) dispersant application is likely to impair cardiac performance.

  2. Specificity and dosimetry of toxicologic responses.

    PubMed

    Doull, J

    1996-08-01

    Toxicology has two goals. The first is to identify and characterize the adverse effects that can be produced in biological systems by exposure to chemicals and the second is to use this information to predict the type and severity of responses in other species and exposure situations. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, subchronic, and chronic studies in animals plus a variety of special studies designed to demonstrate specific organ damage, reproductive and teratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and other responses. These are often supplemented with studies of the kinetics and the mechanism of action and more recently with studies designed to elucidate the molecular basis for cancer and other effects. Theses studies together with the information on exposure provide the basis for subsequent toxicologic predictions. Although general effects such as weight loss and mortality are included in toxicity protocols, most of the toxicology tests are related to specific end-organ toxicity or to mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chemical sensitivity, such as depression, fatigue, headache, and memory loss, and our tests lack sufficient specificity to evaluate a syndrome which is composed primarily of such symptoms. Since all chemicals can produce adverse effects under some conditions of exposure, toxicologic predictions are most useful when they specify both the type of adverse effect anticipated and the dose required to produce the effect. Multiple chemical sensitivity does not appear to consistently involve specific chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely low levels. It is difficult to include these parameters in any reasonable toxicologic prediction relating

  3. Specificity and dosimetry of toxicologic responses.

    PubMed

    Doull, J

    1996-08-01

    Toxicology has two goals. The first is to identify and characterize the adverse effects that can be produced in biological systems by exposure to chemicals and the second is to use this information to predict the type and severity of responses in other species and exposure situations. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, subchronic, and chronic studies in animals plus a variety of special studies designed to demonstrate specific organ damage, reproductive and teratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and other responses. These are often supplemented with studies of the kinetics and the mechanism of action and more recently with studies designed to elucidate the molecular basis for cancer and other effects. Theses studies together with the information on exposure provide the basis for subsequent toxicologic predictions. Although general effects such as weight loss and mortality are included in toxicity protocols, most of the toxicology tests are related to specific end-organ toxicity or to mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chemical sensitivity, such as depression, fatigue, headache, and memory loss, and our tests lack sufficient specificity to evaluate a syndrome which is composed primarily of such symptoms. Since all chemicals can produce adverse effects under some conditions of exposure, toxicologic predictions are most useful when they specify both the type of adverse effect anticipated and the dose required to produce the effect. Multiple chemical sensitivity does not appear to consistently involve specific chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely low levels. It is difficult to include these parameters in any reasonable toxicologic prediction relating

  4. Toxicological effects of polycyclic aromatic hydrocarbons and their derivatives on respiratory cells

    NASA Astrophysics Data System (ADS)

    Koike, Eiko; Yanagisawa, Rie; Takano, Hirohisa

    2014-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are found in ambient aerosols and particulate matter. Experimental studies have shown that PAHs and related chemicals can induce toxicological effects. The present study aimed to investigate the effects of PAHs and their derivatives on the respiratory and immune systems and the underlying mechanisms. The human bronchial epithelial cell line BEAS-2B was exposed to PAHs and their derivatives, and the cytotoxicity and proinflammatory protein expression were then investigated. A cytotoxic effect was observed in BEAS-2B exposed to PAH derivatives such as naphthoquinone (NQ), phenanthrenequinone (PQ), 1-nitropyrene (1-NP), and 1-aminopyrene (1-AP). In addition, 1,2-NQ and 9,10-PQ showed more effective cytotoxicity than 1,4-NQ and 1,4-PQ, respectively. Pyrene showed a weak cytotoxic effect. On the other hand, naphthalene and phenanthrene showed no significant effects. Pyrene, 1-NP, and 1-AP also increased intercellular adhesion molecule-1 expression and interleukin-6 production in BEAS-2B. The increase was partly suppressed by protein kinase inhibitors such as the epidermal growth factor receptor-selective tyrosine kinase inhibitor and nuclear receptor antagonists such as the thyroid hormone receptor antagonist. The present study suggests that the toxicological effects of chemicals may be related to the different activities resulting from their structures, such as numbers of benzene rings and functional groups. Furthermore, the chemical-induced increase in proinflammatory protein expression in bronchial epithelial cells was possibly a result of the activation of protein kinase pathways and nuclear receptors. The increase may partly contribute to the adverse health effects of atmospheric PAHs.

  5. Toxicological and histopathological effects of boric acid on Atta sexdens rubropilosa (Hymenoptera: Formicidae) workers.

    PubMed

    Sumida, Simone; Silva-Zacarin, Elaine C M; Decio, Pâmela; Malaspina, Osmar; Bueno, Fabiana C; Bueno, Odair C

    2010-06-01

    The current study compared the toxicity of different concentrations of boric acid in adult workers of Atta sexdens rubropilosa Forel (Hymenoptera: Formicidae), with toxicological bioassays, and examining the dose-dependent and time-dependent histopathological changes, of the midgut, Malpighian tubules, and postpharyngeal glands. Our results revealed the importance of conducting toxicological bioassays combined with morphological analyses of the organs of ants chronically exposed to insecticides used in commercial ant baits. In vitro bioassays showed that boric acid significantly decreases the survivorship of workers regardless of concentration, whereas the morphological data suggested progressive dose-dependent and time-dependent changes in the organs examined, which were evident in the midgut. The midgut is the first organ to be affected, followed by the postpharyngeal gland and Malpighian tubules. This sequence is in agreement with the absorption pathway of this chemical compound in the midgut, its transference to the hemolymph, possibly reaching the postpharyngeal glands, and excretion by the Malpighian tubules. These progressive changes might be due to the cumulative and delayed effect of boric acid. Our findings provide important information for the understanding of the action of boric acid in ant baits in direct and indirect target organs.

  6. Handbook of toxicology

    SciTech Connect

    Haley, T.J.; Berndt, W.O.

    1987-01-01

    This book discusses the ongoing battle against the effects of pesticides, herbicides, fungicides, and other toxic agents. It points out gaps in present-day research, illustrate other diseases that can mimic chemical toxicity, and emphasize thorough consideration of all aspects in a given incident prior to administering an antidote. The book offers a compiled data on target organ toxicity involving the liver, kidneys, and lungs - detailing the rapid, recent progress in this area. The coverage also highlights reproductive toxicology, food additives, asphixiant gases, and pulmonary toxicology. The partial contents are: Absorption, distribution, Biotransformation, Conjugation, and Excretion of Xenobiotics, Hepatotoxicity, Pulmonary Toxiology, Reproductive and Perinatal toxicology, Toxicology of Insecticides, Rodenticides, Herbicides, and Fungicides, Mechanisms of Metal-Induced Cell Injury, Food Additives: A Benefit/Risk Dilemma, Animal Toxins, and Toxic Effects of Chemicals on the Immune System.

  7. Somatic and heritable effects of environmental genotoxins and the emergence of evolutionary toxicology

    SciTech Connect

    Bickham, J.W.; Smolen, M.J.

    1994-12-01

    The genetic effects of environmental pollutants include mutations in somatic cells or germinal cells that are the direct result of exposure to toxicants. Biomarkers that detect such mutagenic effects have been developed and tested in field studies on wildlife populations. However, another class of genetic effects resulting from pollution exposure exists. Specifically, changes in allele frequencies of populations will occur as a result of population bottlenecks, inbreeding, or selection at loci critical for survival in polluted environments. We describe how such genetic alterations can be studied at the population level using the techniques of molecular genetics, and we predict the development of a new field, evolutionary toxicology, that will address such issues. 26 refs., 1 fig., 1 tab.

  8. Environmental Toxicology

    NASA Astrophysics Data System (ADS)

    Wright, David A.; Welbourn, Pamela

    2002-03-01

    Environmental Toxicology is a comprehensive introductory textbook dealing with most aspects of the subject, from the molecular to the ecosystem level. Early chapters deal with basic to advanced concepts, methods and approaches. The next discusses the environmental toxicology of individual or groups of substances. The third part addresses complex issues, in which many of the concepts, approaches and substances covered in earlier parts are incorporated. The fourth part includes chapters on risk assessment, rehabilitation and regulatory toxicology. The book concludes with a summary of present and future areas of emphasis. Each chapter contains a comprehensive list of references and further reading, case studies from different jurisdictions, and student exercises.

  9. Computational Toxicology

    EPA Science Inventory

    ‘Computational toxicology’ is a broad term that encompasses all manner of computer-facilitated informatics, data-mining, and modeling endeavors in relation to toxicology, including exposure modeling, physiologically based pharmacokinetic (PBPK) modeling, dose-response modeling, ...

  10. Identification and characterization of adverse effects in 21st century toxicology.

    PubMed

    Keller, Douglas A; Juberg, Daland R; Catlin, Natasha; Farland, William H; Hess, Frederick G; Wolf, Douglas C; Doerrer, Nancy G

    2012-04-01

    The practice of toxicology is changing rapidly, as demonstrated by the response to the 2007 NRC report on "Toxicity Testing in the 21(st) Century." New assays are being developed to replace animal testing; yet the use of data from these assays in decision making is not clear. A Health and Environmental Sciences Institute committee held a May 2011 workshop to discuss approaches to identifying adverse effects in the context of the NRC report. Scientists from industry, government, academia, and NGOs discussed two case studies and explored how information from new, high data content assays developed for screening can be used to differentiate adverse effects from adaptive responses. The terms "adverse effect" and "adaptive response" were defined, as well as two new terms, the relevant pathways of toxicological concern (RPTCs) and relevant responses for regulation (RRRs). RPTCs are biochemical pathways associated with adverse events and need to be elucidated before they are used in regulatory decision making. RRRs are endpoints that are the basis for risk assessment and may or may not be at the level of pathways. Workshop participants discussed the criteria for determining whether, at the RPTC level, an effect is potentially adverse or potentially indicative of adaptability, and how the use of prototypical, data-rich compounds could lead to a greater understanding of RPTCs and their use as RRRs. Also discussed was the use of RPTCs in a weight-of-evidence approach to risk assessment. Inclusion of data at this level could decrease uncertainty in risk assessments but will require the use of detailed dosimetry and consideration of exposure context and the time and dose continuum to yield scientifically based decisions. The results of this project point to the need for an extensive effort to characterize RPTCs and their use in risk assessment to make the vision of the 2007 NRC report a reality.

  11. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects

    NASA Astrophysics Data System (ADS)

    Wang, Zhe; Xia, Tian; Liu, Sijin

    2015-04-01

    Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death.

  12. Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects

    PubMed Central

    Wang, Zhe; Xia, Tian; Liu, Sijin

    2015-01-01

    Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death. PMID:25865054

  13. Toxicological assessment of indium nitrate on aquatic organisms and investigation of the effects on the PLHC-1 fish cell line.

    PubMed

    Zurita, Jorge L; Jos, Angeles; del Peso, Ana; Salguero, Manuel; Cameán, Ana M; López-Artíguez, Miguel; Repetto, Guillermo

    2007-11-15

    Indium nitrate is mainly used as a semiconductor in batteries, for plating and other chemical and medical applications. There is a lack of available information about the adverse effects of indium compounds on aquatic organisms. Therefore, the toxic effects on systems from four trophic levels of the aquatic ecosystem were investigated. Firstly, the bacterium Vibrio fischeri, the alga Chlorella vulgaris and the cladoceran Daphnia magna were used in the toxicological evaluation of indium nitrate. The most sensitive model was V. fischeri, with a NOAEL of 0.02 and an EC(50) of 0.04 mM at 15 min. Although indium nitrate should be classified as harmful to aquatic organisms, it is not expected to represent acute risk to the aquatic biota. Secondly, PLHC-1 fish cell line was employed to investigate the effects and mechanisms of toxicity. Although protein content, neutral red uptake, methylthiazol metabolization, lysosomal function and acetylcholinesterase activity were reduced in cells, stimulations were observed for metallothionein levels and succinate dehydrogenase and glucose-6-phosphate dehydrogenase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. To clarify the main events in PLHC-1 cell death induced by indium nitrate, nine modulators were applied. They were related to oxidative stress (alpha-tocopherol succinate, mannitol and sodium benzoate), disruption of calcium homeostasis (BAPTA-AM and EGTA), thiol protection (1,4-dithiotreitol), iron chelation (deferoxiamine) or regulation of glutathione levels (2-oxothiazolidine-4-carboxylic acid and malic acid diethyl ester). The main morphological alterations were hydropic degeneration and loss of cells. At least, in partly, toxicity seems to be mediated by oxidative stress, and particularly by NADPH-dependent lipid peroxidation. PMID:17804041

  14. Toxicological and epidemiological studies on effects of airborne fibers: coherence and public [corrected] health implications.

    PubMed

    Lippmann, Morton

    2014-09-01

    Airborne fibers, when sufficiently biopersistent, can cause chronic pleural diseases, as well as excess pulmonary fibrosis and lung cancers. Mesothelioma and pleural plaques are caused by biopersistent fibers thinner than ∼0.1 μm and longer than ∼5 μm. Excess lung cancer and pulmonary fibrosis are caused by biopersistent fibers that are longer than ∼20 μm. While biopersistence varies with fiber type, all amphibole and erionite fibers are sufficiently biopersistent to cause pathogenic effects, while the greater in vivo solubility of chrysotile fibers makes them somewhat less causal for the lung diseases, and much less causal for the pleural diseases. Most synthetic vitreous fibers are more soluble in vivo than chrysotile, and pose little, if any, health pulmonary or pleural health risk, but some specialty SVFs were sufficiently biopersistent to cause pathogenic effects in animal studies. My conclusions are based on the following: 1) epidemiologic studies that specified the origin of the fibers by type, and especially those that identified their fiber length and diameter distributions; 2) laboratory-based toxicologic studies involving fiber size characterization and/or dissolution rates and long-term observation of biological responses; and 3) the largely coherent findings of the epidemiology and the toxicology. The strong dependence of effects on fiber diameter, length, and biopersistence makes reliable routine quantitative exposure and risk assessment impractical in some cases, since it would require transmission electronic microscopic examination, of representative membrane filter samples, for determining statistically sufficient numbers of fibers longer than 5 and 20 μm, and those thinner than 0.1 μm, based on the fiber types. PMID:25168068

  15. Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum

    SciTech Connect

    Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing Pei Fengkui Li Weisheng; Wu Yijie

    2008-03-15

    Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. However, the pharmaceutical and toxicological effects of cinnabar, especially in the whole organism, were subjected to few investigations. In this study, an NMR-based metabolomics approach has been applied to investigate the toxicological effects of cinnabar after intragastrical administration (dosed at 0.5, 2 and 5 g/kg body weight) on male Wistar rats. Liver and kidney histopathology examinations and serum clinical chemistry analyses were also performed. The {sup 1}H NMR spectra were analyzed using multivariate pattern recognition techniques to show the time- and dose-dependent biochemical variations induced by cinnabar. The metabolic signature of urinalysis from cinnabar-treated animals exhibited an increase in the levels of creatinine, acetate, acetoacetate, taurine, hippurate and phenylacetylglycine, together with a decrease in the levels of trimethyl-N-oxide, dimethylglycine and Kreb's cycle intermediates (citrate, 2-oxoglutarate and succinate). The metabolomics analyses of serum showed elevated concentrations of ketone bodies (3-D-hydroxybutyrate and acetoacetate), branched-chain amino acids (valine, leucine and isoleucine), choline and creatine as well as decreased glucose, lipids and lipoproteins from cinnabar-treated animals. These findings indicated cinnabar induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar induced oxidative stress. This work illustrated the high reliability of NMR-based metabolomic approach on the study of the biochemical effects induced by traditional Chinese medicine.

  16. Toxicology - A primer on toxicology principles and applications

    SciTech Connect

    Kamrin, M.A.

    1988-01-01

    As the use of synthetic chemicals increased dramatically after World War II, concern about the possible adverse health and environmental effects of such use grew. The book opens with a discussion of the general principles of toxicology and how these general principles are applied in assessing the acute, subacute and chronic effects of chemicals. Both qualitative and quantitative measures of toxicity are addressed and the protocols for the various tests are described. Emphasis is placed on both the strengths and limitations of the techniques which are in current use. This is then followed by a discussion of risk assessment and risk management. Risk assessment deals with both the toxic potential of a chemical and the exposure likely to occur in specific situations. Risk management includes the steps taken to reduce or eliminate risks identified in the assessment process. The components of risk assessment are described in relation to a variety of possible toxic effects and exposure scenarios. The last part of the book provides a description and analysis of four case studies, each dealing with a different substance. These include the food additives, cyclamate and saccharin; asbestos; formaldehyde; and benzene. The basic toxicological information regarding each, and the different regulations to which they have been subject, provide the basis for exploring how the principles introduced in the first part of the book are applied in practice.

  17. Magnetic field can alleviate toxicological effect induced by cadmium in mungbean seedlings.

    PubMed

    Chen, Yi-ping; Li, Ran; He, Jun-Min

    2011-06-01

    To alleviate toxicological effect induced by cadmium in mungbean seedlings, seeds were divided into four groups: The controls groups (CK, without treatment), magnetic field treated groups (MF), cadmium treated groups (CS), and magnetic field treated followed by cadmium treated groups (MF + CS).The results showed: (i) Compared with the controls, cadmium stress resulted in enhancing in the concentration of malondialdehyde, H(2)O(2) and O(2-), and the conductivity of electrolyte leakage while decreasing in the nitrice oxide synthase (NOS) activity, the concentration of nitrice oxide (NO), chlorophyll and total carbon and nitrogen, the net photosynthetic rate, the stomatal conductance, the transpiration rate, the water use efficiency, the lateral number and seedlings growth except for intercellular CO(2) concentration increase. However, the seedlings treated with 600 mT magnetic field followed by cadmium stress the concentration of malondialdehyde, H(2)O(2) and O(2-), and the conductivity of electrolyte leakage decreased, while the above mentioned NO concentration, NOS activity, photosynthesis and growth parameters increased compared to cadmium stress alone. (ii) Compared with the cadmium stress (CS), the seedling growth were inhibited when the seeds were treated with NO scavenger (hemoglobin, HB) and inhibition of NO generating enzyme (sodium tungstate, ST), conversely, the seedling growth were improved by the NO donor sodium nitroprusside (SNP) and CaCl(2). In the case of the HB and ST treatment followed by magnetic field and then the seedling subjected to CS, the seedlings growth was better than that of hemoglobin (HB) followed by CS and ST followed by CS. The seeds were treated with SNP and CaCl(2) followed by MF, and then subjected to CS, the seedlings growth were better than that of SNP followed by CS, and CaCl(2) followed by CS. These results suggested that magnetic field compensates for the toxicological effects of cadmium exposure are related to NO signal.

  18. Methods in environmental toxicology (Chapter 20). Book chapter

    SciTech Connect

    Menzer, R.E.; Lewis, M.A.; Fairbrother, A.

    1993-01-01

    By expanding the number of species tested in assessing the toxicology of a chemical one is able to gain considerable insight into its mechanism of action, biodegradability, organ specific toxicity, and acute and potential chronic effects. The expansion of comparative toxicology from reliance on laboratory mammals to the inclusion of feral mammals, fish, birds, and some invertebrates is highly desirable in order to better understand the range of responses to a chemical in its interactions with the various target systems possible in different animals. With the inclusion of additional species in toxicity testing has come the need for the development of protocols to standardize approaches for the use of such new species.

  19. Chemical-chemical interaction between cyanogenic toxicants and aldehydes: a mechanism-based QSAR approach to assess toxicological joint effects.

    PubMed

    Lin, Z; Wei, D; Wang, X; Yin, K; Zhao, D

    2004-04-01

    A QSAR approach was proposed to assess toxicological joint effects based on the mechanism of chemical-chemical interactions between cyanogenic toxicants and aldehydes. It has been observed that the chemical-chemical interaction between cyanogenic toxicants and aldehydes resulted in the formation of carbanion intermediates, and therefore this interaction led to different toxicological joint effects between cyanogenic toxicants and aldehydes. Analysis of this chemical-chemical interaction showed that the formation of carbanion intermediate highly depended on the charge of the carbon atom in the -CHO of aldehydes and this of the carbon atom (C*) in the carbochain of cyanogenic toxicant. By using the Hammett Constant (sigma(p)) to measure the charge of carbon atom in the -CHO of aldehydes, a mechanism-based QSAR approach (M = 0.316 - 4.386sigma(p) with r2 = 0.933, SE = 0.082, F = 55.389, p = 0.002, M = sum of toxic units) was proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aliphatic aldehydes. Another one (M = 0.978 - 0.720sigma(p) with r2 = 0.852, SE = 0.152, F = 40.148, p = 0.0001) was also proposed to assess the toxicological joint effects between alpha-hydroxy-isobutyronitrile and individual aromatic aldehydes. Lastly, by using the charge of carbon atom (C*) in the carbochain of cyanogenic toxicant, a mechanism-based QSAR model (M = -0.161 - 7.721C* with r2 = 0.847, SE = 0.227, F = 27.657, p = 0.003) was derived to assess toxicological joint effects between p-nitrobenzaldehyde and cyanogenic toxicants.

  20. Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles in the United States.

    PubMed

    Ming-Ch'eng Adams, Clare Isabel; Baker, Joel E; Kjellerup, Birthe V

    2016-07-01

    Prediction of vertebrate health effects originating from persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a challenge for decades thus making the identification of bioindicators difficult. POPs are predominantly present in soil and sediment, where they adhere to particles due to their hydrophobic characteristics. Animals inhabiting soil and sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs through contaminated trophic interaction. Freshwater turtles can serve as bioindicators due to their strong site fidelity, longevity and varied diet. Previous research observed the health effects of PCBs on turtles such as decreased bone mass, changed sexual development and decreased immune responses through studying both contaminated sites along with laboratory experimentation. Higher deformity rates in juveniles, increased mortality and slower growth have also been observed. Toxicological effects of PCBs vary between species of freshwater turtles and depend on the concertation and configuration of PCB congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered turtles could provide important knowledge about the health effects of endangered turtle species thus inform the design of remediation strategies. In this review, the PCB presence in freshwater turtle habitats and the ecotoxicological effects were investigated with the aim of utilizing the health status to identify areas of focus for freshwater turtle conservation. PMID:27043381

  1. Toxicological effects of polychlorinated biphenyls (PCBs) on freshwater turtles in the United States.

    PubMed

    Ming-Ch'eng Adams, Clare Isabel; Baker, Joel E; Kjellerup, Birthe V

    2016-07-01

    Prediction of vertebrate health effects originating from persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) has remained a challenge for decades thus making the identification of bioindicators difficult. POPs are predominantly present in soil and sediment, where they adhere to particles due to their hydrophobic characteristics. Animals inhabiting soil and sediment can be exposed to PCBs via dermal exposure while others may obtain PCBs through contaminated trophic interaction. Freshwater turtles can serve as bioindicators due to their strong site fidelity, longevity and varied diet. Previous research observed the health effects of PCBs on turtles such as decreased bone mass, changed sexual development and decreased immune responses through studying both contaminated sites along with laboratory experimentation. Higher deformity rates in juveniles, increased mortality and slower growth have also been observed. Toxicological effects of PCBs vary between species of freshwater turtles and depend on the concertation and configuration of PCB congeners. Evaluation of ecotoxicological effects of PCBs in non-endangered turtles could provide important knowledge about the health effects of endangered turtle species thus inform the design of remediation strategies. In this review, the PCB presence in freshwater turtle habitats and the ecotoxicological effects were investigated with the aim of utilizing the health status to identify areas of focus for freshwater turtle conservation.

  2. The toxicology of chemosterilants

    PubMed Central

    Hayes, Wayland J.

    1964-01-01

    Sterilization of males can in certain circumstances be more efficient than killing as a method for control of insects and perhaps other pests. A number of chemicals (chemosterilants) show promise of producing sexual sterility in insects without some of the practical limitations of radiation. The most important compounds are alkylating agents. These have little immediate pharmacological action, but are notable for their selective action against haematopoietic and some other proliferating tissues. A number of alkylating agents have been shown to be mutagens in insects, bacteria, fungi, and higher plants; carcinogens in mammals; and teratogens in insects, birds, and mammals. Some produce sexual sterility, possibly in mammals as well as in insects, at doses too low to produce the other effects. Some have an established reputation as drugs for palliative treatment of leukaemia and other neoplasms. The development of insect sterilization as a vector control technique has been handicapped in part by lack of scientific information on the acute and long-term hazards that might be associated with the use of chemosterilants. In this paper the author brings together the available knowledge on the toxicology of the alkylating agents. PMID:14278008

  3. Toxicology: Old Art, New Science.

    ERIC Educational Resources Information Center

    Timbrell, John A.

    1983-01-01

    Examines the need for a science of toxicology and training at both the undergraduate and graduate levels in response to legislation controlling drugs, food additives and toxic substances in the work environment, and concern about effects on man. Stresses need for putting toxicology on a scientific base with adequate funding. (JM)

  4. Acute and Subacute Toxicological Evaluation of the Aerial Extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar Rats

    PubMed Central

    2016-01-01

    The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment-related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose-dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment-facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study.

  5. Acute and Subacute Toxicological Evaluation of the Aerial Extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar Rats.

    PubMed

    Afolayan, Anthony Jide; Wintola, Olubunmi Abosede; Fouche, Gerda

    2016-01-01

    The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment-related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose-dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment-facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study. PMID:27672399

  6. Acute and Subacute Toxicological Evaluation of the Aerial Extract of Monsonia angustifolia E. Mey. ex. A. Rich in Wistar Rats

    PubMed Central

    2016-01-01

    The acute and subacute toxicity profile of the aerial extract of Monsonia angustifolia in Wistar rats was evaluated. The Organization for Economic Cooperation and Development (OECD) 420 guideline was adopted in the acute toxicity testing with a single oral dose of 5000 mg/kg (b.w.). For the 28-day daily oral dosing, the extract was administered at 75, 150, and 300 mg/kg b.w.; 1% ethanol in sterile distilled water was used as control. Clinical toxicity signs were subsequently evaluated. At a single dose of 5000 mg/kg b.w. the extract elicited no treatment-related signs of toxicity in the animals during the 14 days of experimental period. In the subacute toxicity, there was no significant difference in hematological, renal, and liver function indices. However, dose-dependent significant increases were observed on the plasma concentrations of white blood cell and platelet counts of the treated animals compared to the control group. While cage observations revealed no treatment-facilitated signs of toxicity, histopathological examinations of the kidneys and liver also showed no obvious lesions and morphological changes. These results suggest that the extract may be labelled and classified as safe and practically nontoxic within the doses and period of investigation in this study. PMID:27672399

  7. Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents.

    PubMed

    Antonelli-Ushirobira, T M; Kaneshima, E N; Gabriel, M; Audi, E A; Marques, L C; Mello, J C P

    2010-07-01

    We evaluated the toxicity of a semipurified extract (EPA fraction, containing caffeine and several flavan-3-ols and proanthocyanidins) of seeds of the native Amazon plant Paullinia cupana (guaraná) in rodents. Acute toxicity was tested in male Swiss mice, which received different doses orally (OR) and intraperitoneally (ip); control groups received water. These tests produced acute mortality, with LD(50) of 1.825 g/kg (OR) and 0.827 g/kg (ip), and a significant weight decrease in lungs of mice receiving a dose of 0.1g/kg. In the repeated-dose toxicity test, the EPA was administered OR daily to male and female Wistar rats at doses of 30, 150, and 300 mg/kg/day/90 days. Their behavior, mortality, weight changes, laboratory tests, and the weights and histopathology of organs were evaluated. No rats died during the tests. Males dosed at 150 or 300 mg/kg gained weight more slowly and lost kidney weight (absolute and relative weights, compared to the control group). Hematological and biochemical tests showed few changes, differing somewhat between males and females; the histopathological evaluation indicated no significant changes. These results indicate that the EPA fraction of guaraná caused no toxicity in rats at the smallest dose evaluated (30 mg/kg). No other species was evaluated.

  8. Comparative proteomic profiling and possible toxicological mechanism of acute injury induced by carbon ion radiation in pubertal mice testes

    NASA Astrophysics Data System (ADS)

    Zhang, Hong

    2016-07-01

    We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation

  9. Aerospace Toxicology and Microbiology

    NASA Technical Reports Server (NTRS)

    James, John T.; Parmet, A. J.; Pierson, Duane L.

    2007-01-01

    Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

  10. The behavior and toxicological effects of decabromodiphenyl ether (BDE209) in a soil-earthworm system.

    PubMed

    Zhang, Wei; Li, Jing; Liu, Kou; Lin, Kuangfei

    2015-12-15

    Decabromodiphenyl ether (BDE209) is easily absorbed by soil particles but barely degraded over time. Its potential ecological risk has received extensive attention. Here we supplemented natural soil with three different levels of BDE209 (1, 10 and 100 mg kg(-1) dry weight (i.e., dw)) to focus on the behavior and toxicological effects of BDE209 in a soil-earthworm system. Results demonstrated that earthworms accumulated BDE209 quickly, followed by biphasic elimination. The uptake rate constant (ku) values ranged from 0.156 to 0.232 mg soil kg(-1)worm d(-1), while the depuration rate (kd) values ranged from 0.228 to 0.239 d(-1). Biota-soil accumulation factor (BSAF) was also calculated in the present study, and the BSAF values for BDE209 ranged from 0.074 to 0.123. Throughout 28-d exposure, the concentrations of BDE209 among soil, worm casts and earthworms reached steady-state equilibrium. BDE209 content in worm casts might be a good indicator of actual concentration in soil. Neutral red retention time (NRRT) was also conducted to assess the lysosomal membrane stability, and it declined during the uptake phase when BDE209 gradually accumulated in earthworms, indicating a good dose-response relationship. These observations provide new insights into the potential ecological effects of BDE209 in a model soil-earthworm system.

  11. Toxicological effects of nanometer titanium dioxide (nano-TiO2) on Chlamydomonas reinhardtii.

    PubMed

    Chen, Lanzhou; Zhou, Lina; Liu, Yongding; Deng, Songqiang; Wu, Hao; Wang, Gaohong

    2012-10-01

    The toxicological effects of nanometer titanium dioxide (nano-TiO2) on a unicellular green alga Chlamydomonas reinhardtii were assessed by investigating the changes of the physiology and cyto-ultrastructure of this species under treatment. We found that nano-TiO2 inhibited photosynthetic efficiency and cell growth, but the content of chlorophyll a content in algae did not change, while carotenoid and chlorophyll b contents increased. Malondialdehyde (MDA) content reached maximum values after 8h exposure and then decreased to a moderately low level at 72 h. Electron microscopy images indicated that as concentrations of nano-TiO2 increased, a large number of C. reinhardtii cells were noted to be damaged: the number of chloroplasts declined, various other organelles were degraded, plasmolysis occurred, and TiO2 nanoparticles were found to be located inside cell wall and membrane. It was also noted that cell surface was surrounded by TiO2 particles, which could present an obstacle to the exchange of substances between the cell and its surrounding environment. To sum up, the effect of nano-TiO2 on C. reinhardtii included cell surface aggregation, photosynthesis inhibition, lipid peroxidation and new protein synthesis, while the response of C. reinhardtii to nano-TiO2 was a rapid process which occurs during 24 h after exposing and may relate to physiological stress system to mitigate damage. PMID:22883605

  12. Transformation of Air Quality Monitor Data from the International Space Station into Toxicological Effect Groups

    NASA Technical Reports Server (NTRS)

    James, John T.; Zalesak, Selina M.

    2011-01-01

    The primary reason for monitoring air quality aboard the International Space Station (ISS) is to determine whether air pollutants have collectively reached a concentration where the crew could experience adverse health effects. These effects could be near-real-time (e.g. headache, respiratory irritation) or occur late in the mission or even years later (e.g. cancer, liver toxicity). Secondary purposes for monitoring include discovery that a potentially harmful compound has leaked into the atmosphere or that air revitalization system performance has diminished. Typical ISS atmospheric trace pollutants consist of alcohols, aldehydes, aromatic compounds, halo-carbons, siloxanes, and silanols. Rarely, sulfur-containing compounds and alkanes are found at trace levels. Spacecraft Maximum Allowable Concentrations (SMACs) have been set in cooperation with a subcommittee of the National Research Council Committee on Toxicology. For each compound and time of exposure, the limiting adverse effect(s) has been identified. By factoring the analytical data from the Air Quality Monitor (AQM), which is in use as a prototype instrument aboard the ISS, through the array of compounds and SMACs, the risk of 16 specific adverse effects can be estimated. Within each adverse-effect group, we have used an additive model proportioned to each applicable 180-day SMAC to estimate risk. In the recent past this conversion has been performed using archival data, which can be delayed for months after an air sample is taken because it must be returned to earth for analysis. But with the AQM gathering in situ data each week, NASA is in a position to follow toxic-effect groups and correlate these with any reported crew symptoms. The AQM data are supplemented with data from real-time CO2 instruments aboard the ISS and from archival measurements of formaldehyde, which the AQM cannot detect.

  13. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    SciTech Connect

    Prouillac, Caroline; Lecoeur, Sylvaine

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  14. Saraca indica Bark Extract Shows In Vitro Antioxidant, Antibreast Cancer Activity and Does Not Exhibit Toxicological Effects

    PubMed Central

    Yadav, Navneet Kumar; Saini, Karan Singh; Hossain, Zakir; Omer, Ankur; Sharma, Chetan; Gayen, Jiaur R.; Singh, Poonam; Arya, K. R.; Singh, R. K.

    2015-01-01

    Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy. PMID:25861411

  15. Saraca indica bark extract shows in vitro antioxidant, antibreast cancer activity and does not exhibit toxicological effects.

    PubMed

    Yadav, Navneet Kumar; Saini, Karan Singh; Hossain, Zakir; Omer, Ankur; Sharma, Chetan; Gayen, Jiaur R; Singh, Poonam; Arya, K R; Singh, R K

    2015-01-01

    Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy.

  16. Science: Aquatic Toxicology Matures, Gains Importance.

    ERIC Educational Resources Information Center

    Dagani, Ron

    1980-01-01

    Reviews recent advances in aquatic toxicology, whose major goal is to protect diverse aquatic organisms and whole ecological communities from the dire effects of man-made chemicals. Current legislation is reviewed. Differences in mammalian and aquatic toxicology are listed, and examples of research in aquatic toxicology are discussed. (CS)

  17. Effect of oxygenated fuels on physicochemical and toxicological characteristics of diesel particulate emissions.

    PubMed

    Zhang, Zhi-Hui; Balasubramanian, Rajasekhar

    2014-12-16

    A systematic study was conducted to make a comparative evaluation of the effects of blending five different oxygenates (diglyme (DGM), palm oil methyl ester (PME), dimethyl carbonate (DMC), diethyl adipate (DEA), and butanol (Bu)) with ultralow sulfur diesel (ULSD) at 2% and 4% oxygen levels on physicochemical and toxicological characteristics of particulate emissions from a nonroad diesel engine. All blended fuels led to an overall decrease in the particulate mass concentration and elemental carbon (EC) emissions, which was strongly associated with the oxygen content in fuels and the specific type of fuels used. In general, the proportion of particulate-bound organic carbon (OC) and water-soluble organic carbon (WSOC) increased while using oxygenated fuel blends. Compared to ULSD, all fuel blends showed different emission factors of particle-phase PAHs and n-alkanes, slight alterations in soot nanostructure, lower soot ignition temperature, and lower activation energy. The total counts of particles (≤ 560 nm diameter) emitted decreased gradually for ULSD blended with DMC, DEA, and Bu, while they increased significantly for other fuel blends. The in vitro toxicity of particulates significantly increased with ULSD blended with DMC and DEA, while it decreased when ULSD was blended with PME, DGM, and Bu. PMID:25383974

  18. Toxicological effects of short-term dietary acrylamide exposure in male F344 rats.

    PubMed

    Raju, Jayadev; Roberts, Jennifer; Taylor, Marnie; Patry, Dominique; Chomyshyn, Emily; Caldwell, Don; Cooke, Gerard; Mehta, Rekha

    2015-01-01

    We recently reported that acrylamide, a known rodent and probable human carcinogen, does not increase the risk of azoxymethane (AOM)-induced rat colon precancerous lesions when administered through the diet. Here, we present toxicological data from non-AOM-injected rats. Briefly, male F344 rats were randomized into four dietary groups and received experimental diets based on AIN-93G formulation and containing acrylamide at 0 (control), 5, 10 or 50mg/kg diet (wt/wt) ad libitum for 10 weeks, after which they were killed and their blood collected for hematological and biochemical markers. Acrylamide at the higher doses (10 and 50mg/kg diet) significantly lowered (p<0.05) serum total high density lipoprotein and total testosterone and increased serum lipase in comparison to the control. Blood hematocrit values and lymphocyte counts were significantly lower (p<0.05) in the high dose acrylamide (50mg/kg diet) group compared to control, with a concomitant decrease in hemoglobin level, mean corpuscular volume and mean corpuscular hemoglobin. These results provide additional hazard characterization data and strengthen the notion that at high doses, acrylamide may involve systemic toxicity potentiating tumorigenesis in experimental animals. Further studies are required to understand the health effects of food-borne acrylamide, especially at the lower exposures typified by human diets.

  19. Ecological and toxicological effects of inorganic nitrogen pollution in aquatic ecosystems: A global assessment.

    PubMed

    Camargo, Julio A; Alonso, Alvaro

    2006-08-01

    We provide a global assessment, with detailed multi-scale data, of the ecological and toxicological effects generated by inorganic nitrogen pollution in aquatic ecosystems. Our synthesis of the published scientific literature shows three major environmental problems: (1) it can increase the concentration of hydrogen ions in freshwater ecosystems without much acid-neutralizing capacity, resulting in acidification of those systems; (2) it can stimulate or enhance the development, maintenance and proliferation of primary producers, resulting in eutrophication of aquatic ecosystems; (3) it can reach toxic levels that impair the ability of aquatic animals to survive, grow and reproduce. Inorganic nitrogen pollution of ground and surface waters can also induce adverse effects on human health and economy. Because reductions in SO2 emissions have reduced the atmospheric deposition of H2SO4 across large portions of North America and Europe, while emissions of NOx have gone unchecked, HNO3 is now playing an increasing role in the acidification of freshwater ecosystems. This acidification process has caused several adverse effects on primary and secondary producers, with significant biotic impoverishments, particularly concerning invertebrates and fishes, in many atmospherically acidified lakes and streams. The cultural eutrophication of freshwater, estuarine, and coastal marine ecosystems can cause ecological and toxicological effects that are either directly or indirectly related to the proliferation of primary producers. Extensive kills of both invertebrates and fishes are probably the most dramatic manifestation of hypoxia (or anoxia) in eutrophic and hypereutrophic aquatic ecosystems with low water turnover rates. The decline in dissolved oxygen concentrations can also promote the formation of reduced compounds, such as hydrogen sulphide, resulting in higher adverse (toxic) effects on aquatic animals. Additionally, the occurrence of toxic algae can significantly

  20. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    PubMed Central

    Koch, Karoline; Havermann, Susannah; Büchter, Christian

    2014-01-01

    Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

  1. Advanced urine toxicology testing.

    PubMed

    Tenore, Peter L

    2010-10-01

    Urine toxicology screening testing is an important standard of care in the addiction and pain treatment setting, offering a reproducible, unbiased, and accurate laboratory test to monitor patients and provide objective support for clinical observations. It has been shown that physicians do not have proficiency in the ordering or interpretation of these tests. This article is an attempt to respond to that need. Current antibody-based enzymatic immunoassays (EIAs) used for urine toxicology screening are useful to detect classes of drugs (ex., opiate) but cannot determine which specific drug (ex., morphine) is present. Gas chromatography and mass spectroscopy can determine exactly which drugs are present, allowing prescribed (or illicit) opiates and benzodiazepines to be identified. This article will discuss principles and details of opiate and benzodiazepine EIA and gas chromatography and mass spectroscopy urine toxicology testing. The approach to detecting patients attributing positive opiate EIAs to prescription opiates who are using heroin or other opioids will be reviewed. Cases of controlled prescription drugs that do not produce the expected positive urine tests (ex., oxycodone producing negative opiate screening tests) will be discussed. How to differentiate codeine from heroin and the role of poppy seeds in toxicology will be examined. The case of an anti-depressant drug that produces false-positive benzodiazepine results and antibiotics that cause positive opiate urine toxicology results will be reviewed. Common benzodiazepines (ex., clonazepam and lorazepam) that do not reliably produce positive benzodiazepine EIAs will be discussed. The approach to detection and management of all these types of toxicology cases will be reviewed, and it is hoped that the analyses presented will impart an adequate information base to medical providers and staff members of drug treatment and pain centers, enabling them to order and interpret these tests in the clinic more

  2. Toxicology and Chemical Safety.

    ERIC Educational Resources Information Center

    Hall, Stephen K.

    1983-01-01

    Topics addressed in this discussion of toxicology and chemical safety include routes of exposure, dose/response relationships, action of toxic substances, and effects of exposure to chemicals. Specific examples are used to illustrate the principles discussed. Suggests prudence in handling any chemicals, whether or not toxicity is known. (JN)

  3. Arsenic Exposure and Toxicology: A Historical Perspective

    PubMed Central

    Hughes, Michael F.; Beck, Barbara D.; Chen, Yu; Lewis, Ari S.; Thomas, David J.

    2011-01-01

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve. PMID:21750349

  4. High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

    PubMed Central

    Marescotti, Diego; Gonzalez Suarez, Ignacio; Acali, Stefano; Johne, Stephanie; Laurent, Alexandra; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C.

    2016-01-01

    Cigarette smoke (CS) is a major risk factor for cardiovascular and lung diseases. Because CS is a complex aerosol containing more than 7,000 chemicals1 it is challenging to assess the contributions of individual constituents to its overall toxicity. Toxicological profiles of individual constituents as well as mixtures can be however established in vitro, by applying high through-put screening tools, which enable the profiling of Harmful and Potentially Harmful Constituents (HPHCs) of tobacco smoke, as defined by the U.S. Food and Drug Administration (FDA).2 For an initial assessment, an impedance-based instrument was used for a real-time, label-free assessment of the compound's toxicity. The instrument readout relies on cell adhesion, viability and morphology that all together provide an overview of the cell status. A dimensionless parameter, named cell index, is used for quantification. A set of different staining protocols was developed for a fluorescence imaging-based investigation and a HCS platform was used to gain more in-depth information on the kind of cytotoxicity elicited by each HPHC. Of the 15 constituents tested, only five were selected for HCS-based analysis as they registered a computable LD50 (< 20 mM). These included 1-aminonaphtalene, Arsenic (V), Chromium (VI), Crotonaldehyde and Phenol. Based on their effect in the HCS, 1-aminonaphtalene and Phenol could be identified to induce mitochondrial dysfunction, and, together with Chromium (VI) as genotoxic based on the increased histone H2AX phosphorylation. Crotonaldehyde was identified as an oxidative stress inducer and Arsenic as a stress kinase pathway activator. This study demonstrates that a combination of impedance-based and HCS technologies provides a robust tool for in vitro assessment of CS constituents. PMID:27228213

  5. Toxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Sediment-Associated Biota

    SciTech Connect

    Hull, R.N.

    1993-01-01

    A hazardous waste site may contain hundreds of chemicals; therefore, it is important to screen contaminants of potential concern for the ecological risk assessment. Often this screening is done as part of a screening assessment, the purpose of which is to evaluate the available data, identify data gaps, and screen contaminants of potential concern. Screening may be accomplished by using a set of toxicological benchmarks. These benchmarks are helpful in determining whether contaminants warrant further assessment or are at a level that requires no further attention. If a chemical concentration or the reported detection limit exceeds a proposed lower benchmark, further analysis is needed to determine the hazards posed by that chemical. If, however, the chemical concentration falls below the lower benchmark value, the chemical may be eliminated from further study. The use of multiple benchmarks is recommended for screening chemicals of concern in sediments. Integrative benchmarks developed for the National Oceanic and Atmospheric Administration and the Florida Department of Environmental Protection are included for inorganic and organic chemicals. Equilibrium partitioning benchmarks are included for screening nonionic organic chemicals. Freshwater sediment effect concentrations developed as part of the U.S. Environmental Protection Agency's (EPA's) Assessment and Remediation of Contaminated Sediment Project are included for inorganic and organic chemicals (EPA 1996). Field survey benchmarks developed for the Ontario Ministry of the Environment are included for inorganic and organic chemicals. In addition, EPA-proposed sediment quality criteria are included along with screening values from EPA Region IV and Ecotox Threshold values from the EPA Office of Solid Waste and Emergency Response. Pore water analysis is recommended for ionic organic compounds; comparisons are then made against water quality benchmarks. This report is an update of three prior reports (Jones et al

  6. Genetic toxicology.

    PubMed

    Kramer, P J

    1998-04-01

    Systems for testing genetic toxicology are components of carcinogenic and genetic risk assessment. Present routine genotoxicity-testing is based on at least 20 years of development during which many different test systems have been introduced and used. Today, it is clear that no single test is capable of detecting all genotoxic agents. Therefore, the usual approach is to perform a standard battery of in-vitro and in-vivo tests for genotoxicity. Work-groups of the European Union (EU), the Organization for Economic Co-operation and Development (OECD), and, very recently, the work-group of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have defined such standard battery tests. These and some currently used supplementary or confirmatory tests are briefly discussed here. Additional test systems for the assessment of genotoxic and carcinogenic hazard and risk are seriously needed. These tests must be more relevant to man than are current assays and less demanding in respect of cost, time and number of animals. Another aspect for reassessment derives from the actual situation in the pharmaceutical industry. Companies have to prepare for the world economy of the 21st century. Therefore, pharmaceutical research is speeding up tremendously by use of tools such as genomics, combinatorial chemistry, high throughput screening and proteomics. Toxicology and genotoxicology need to re-evaluate their changing environment and must find ways to respond to these needs. In conclusion, genetic toxicology needs to answer questions coming from two major directions: hazard and risk identification and high throughput testing. PMID:9625484

  7. Acute Exposure to Particulate Matter (PM) Alters Physiologic and Toxicologic Endpoints in a Rat Model of Heart Failure

    EPA Science Inventory

    Human exposure to ambient PM from fossil-fuel emissions is linked to cardiovascular disease and death. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). We previously examined the effects of PM on HF by exposing Sponta...

  8. Toxicology of Biodiesel Combustion products

    EPA Science Inventory

    1. Introduction The toxicology of combusted biodiesel is an emerging field. Much of the current knowledge about biological responses and health effects stems from studies of exposures to other fuel sources (typically petroleum diesel, gasoline, and wood) incompletely combusted. ...

  9. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    SciTech Connect

    Hartung, R.

    1995-12-31

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab.

  10. Toxicological benchmarks for screening potential contaminants of concern for effects on aquatic biota: 1994 Revision

    SciTech Connect

    Suter, G.W. II; Mabrey, J.B.

    1994-07-01

    This report presents potential screening benchmarks for protection of aquatic life from contaminants in water. Because there is no guidance for screening benchmarks, a set of alternative benchmarks is presented herein. The alternative benchmarks are based on different conceptual approaches to estimating concentrations causing significant effects. For the upper screening benchmark, there are the acute National Ambient Water Quality Criteria (NAWQC) and the Secondary Acute Values (SAV). The SAV concentrations are values estimated with 80% confidence not to exceed the unknown acute NAWQC for those chemicals with no NAWQC. The alternative chronic benchmarks are the chronic NAWQC, the Secondary Chronic Value (SCV), the lowest chronic values for fish and daphnids from chronic toxicity tests, the estimated EC20 for a sensitive species, and the concentration estimated to cause a 20% reduction in the recruit abundance of largemouth bass. It is recommended that ambient chemical concentrations be compared to all of these benchmarks. If NAWQC are exceeded, the chemicals must be contaminants of concern because the NAWQC are applicable or relevant and appropriate requirements (ARARs). If NAWQC are not exceeded, but other benchmarks are, contaminants should be selected on the basis of the number of benchmarks exceeded and the conservatism of the particular benchmark values, as discussed in the text. To the extent that toxicity data are available, this report presents the alternative benchmarks for chemicals that have been detected on the Oak Ridge Reservation. It also presents the data used to calculate benchmarks and the sources of the data. It compares the benchmarks and discusses their relative conservatism and utility.

  11. Toxicological evaluation of aerosols of a tobacco extract formulation and nicotine formulation in acute and short-term inhalation studies.

    PubMed

    Werley, Michael S; Jerome, Ann M; Oldham, Michael J

    2014-03-01

    A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine formulation containing vehicle and 4% nicotine (NF) were evaluated using animal inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure concentrations, respectively, of the tobacco extract with 4% nicotine formulation showed that the LC50 was greater than 2 mg/L, the maximum concentration tested. All inhalation exposures were conducted using the capillary aerosol generator (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and 0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose groups of male and female rats for 4-h per day for 14 days. In life monitors for potential effects included clinical observations, weekly body weights and food consumption. Post mortem evaluations included gross tissue findings, hematology, clinical chemistry, serum plasma and nicotine levels, absolute and normalized organ and tissue weights, and histopathology of target organs. Treatment-related changes were observed in body weights, hematology, clinical chemistry, organ weights and histopathological findings for TE at the 200 and 1000 mg/m(3) exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under the conditions of these studies, the no-observed-adverse-effect level in the rat was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately 200 mg/m(3) in the NF aerosol-exposed groups.

  12. Acute marijuana effects on social conversation.

    PubMed

    Higgins, S T; Stitzer, M L

    1986-01-01

    The present study assessed the acute effects of smoked marijuana on social conversation. Speech quantity was recorded continuously in seven moderate marijuana users during separate 1 h experimental sessions following the paced smoking of 0, 1.01, 1.84, and 2.84% THC marijuana cigarettes. Subjects engaged in conversation with undrugged partners who smoked placebo marijuana cigarettes. The active marijuana produced significant decreases in speech quantity, increases in heart rate, and increases in self-reports of "high" and sedation. Partners showed no effects in speech quantity or self-reports of drug effects that were systematically related to the doses administered to the subject pair members. The effects on speech quantity observed in the present study after acute dosing are similar to the effects on social conversation reported previously during chronic marijuana dosing. Marijuana appears to be an exception to the general rule that drugs of abuse increase verbal interaction.

  13. Effects of coal rank on the chemical composition and toxicological activity of coal liquefaction materials

    SciTech Connect

    Wright, C.W.; Dauble, D.D.

    1986-05-01

    This report presents data from the chemical analysis and toxicological testing of coal liquefaction materials from the EDS and H-Coal processes operated using different ranks of coal. Samples of recycle solvent from the bottoms recycle mode of the EDS direct coal liquefaction process derived from bituminous, sub-bituminous, and lignite coals were analyzed. In addition, the H-Coal heavy fuel oils derived from bituminous and sub-bituminous coals were analyzed. Chemical methods of analysis included adsoprtion column chromatography, high-resolution gas chromatography, gas chromatography/mass spectrometry, and low-voltage probe-inlet mass spectrometry. The toxicological activity of selected samples was evaluated using the standard microbial mutagenicity assay, an initiation/promotion assay for mouse-skin tumorigenicity, and a static bioassy with Daphnia magna for aquatic toxicity of the water-soluble fractions. 22 refs., 16 figs., 14 tabs.

  14. Ecological and toxicological effects of inorganic nitrogen pollution in aquatic ecosystems: A global assessment.

    PubMed

    Camargo, Julio A; Alonso, Alvaro

    2006-08-01

    We provide a global assessment, with detailed multi-scale data, of the ecological and toxicological effects generated by inorganic nitrogen pollution in aquatic ecosystems. Our synthesis of the published scientific literature shows three major environmental problems: (1) it can increase the concentration of hydrogen ions in freshwater ecosystems without much acid-neutralizing capacity, resulting in acidification of those systems; (2) it can stimulate or enhance the development, maintenance and proliferation of primary producers, resulting in eutrophication of aquatic ecosystems; (3) it can reach toxic levels that impair the ability of aquatic animals to survive, grow and reproduce. Inorganic nitrogen pollution of ground and surface waters can also induce adverse effects on human health and economy. Because reductions in SO2 emissions have reduced the atmospheric deposition of H2SO4 across large portions of North America and Europe, while emissions of NOx have gone unchecked, HNO3 is now playing an increasing role in the acidification of freshwater ecosystems. This acidification process has caused several adverse effects on primary and secondary producers, with significant biotic impoverishments, particularly concerning invertebrates and fishes, in many atmospherically acidified lakes and streams. The cultural eutrophication of freshwater, estuarine, and coastal marine ecosystems can cause ecological and toxicological effects that are either directly or indirectly related to the proliferation of primary producers. Extensive kills of both invertebrates and fishes are probably the most dramatic manifestation of hypoxia (or anoxia) in eutrophic and hypereutrophic aquatic ecosystems with low water turnover rates. The decline in dissolved oxygen concentrations can also promote the formation of reduced compounds, such as hydrogen sulphide, resulting in higher adverse (toxic) effects on aquatic animals. Additionally, the occurrence of toxic algae can significantly

  15. GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.

    PubMed

    Busardò, Francesco P; Jones, Alan W

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  16. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    PubMed Central

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  17. Toxicological effects of CdSe/ZnS quantum dots on marine planktonic organisms.

    PubMed

    Zhou, Chao; Vitiello, Valentina; Pellegrini, David; Wu, Changwen; Morelli, Elisabetta; Buttino, Isabella

    2016-01-01

    Quantum dot nanoparticles (QDs) are proposed as novel materials for photovoltaic technologies, light emitting devices, and biomedical applications. In this study we investigated the effect of CdSe/ZnS QDs on the growth rate of four microalgae: the diatom Phaeodactylum tricornutum, the cryptophyte Rhinomonas reticulata, the prymnesiophyte Isochrysis galbana and the green alga Dunaliella tertiolecta. In addition we analyzed the effect of QDs on the copepod Acartia tonsa. A classical acute test (48-h) with embryos was carried out to evaluate naupliar survival. Moreover, a 4-day chronic test with adult copepods was conducted to evaluate their fecundity (embryos f(-1)day(-1)) and egg hatching success. QDs in the range from 1 to 4nM gradually inhibited the growth rate of P. tricornutum, I. galbana, R. reticulata and D. tertiolecta with an EC50 of 1.5, 2.4, 2.5 and 4.2nM, respectively. Acute tests with A. tonsa (QD concentration tested from 0.15 to 1.5nM) showed an increased naupliar mortality in response to QD treatment, exhibiting an EC50 of 0.7nM. Chronic test showed no negative effect on egg production, except on the last two days at the highest QD concentration (2.5nM). No significant reduction of the percentage of egg hatching success was recorded during the exposure. Toxicity assessment of QDs was also investigated at the molecular level, studying heat shock protein 70 gene expression (hsp 70). Our results indicate that hsp70 was upregulated in adults exposed 3 days to 0.5nM QDs. Overall, these results suggest that species unable to swim along the water column, like P. tricornutum and early hatched copepods, could be more exposed to toxic effects of QDs which tend to aggregate and settle in seawater. PMID:26409651

  18. Toxicologic evaluation of ofloxacin.

    PubMed

    Davis, G J; McKenzie, B E

    1989-12-29

    Results of studies conducted to characterize local, systemic, reproductive, and mutagenic effects indicate that ofloxacin is well tolerated within reasonable multiples of the intended clinical dose. Quinolone-associated arthropathic effects characterized by blister, erosion, and increased synovial fluid occurred in rats and dogs and appeared to be both age- and dose-related. Maternal toxicity and embryotoxicity were noted, but there was no teratogenicity in rats or rabbits. There was no impairment of fertility, and no adverse effects on late fetal development, labor, delivery, lactation, neonatal viability, or growth of offspring occurred. Target-organ studies revealed no evidence of ocular toxicity in rats, nephrotoxicity in rabbits, or antigenicity or ototoxicity in guinea pigs. Overall, the toxicologic evaluation of ofloxacin has shown this compound to be a drug with a low toxicologic potential.

  19. Systems toxicology.

    PubMed

    Hartung, Thomas; van Vliet, Erwin; Jaworska, Joanna; Bonilla, Leo; Skinner, Nigel; Thomas, Russell

    2012-01-01

    The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity. PMID:22562485

  20. In vitro sensitivity of granulo-monocytic progenitors as a new toxicological cell system and endpoint in the ACuteTox Project

    SciTech Connect

    Cerrato, Laura; Valeri, Antonio; Bueren, Juan A.; Albella, Beatriz

    2009-07-15

    The ACuteTox Project (part of the EU 6th Framework Programme) was started up in January 2005. The aim of this project is to develop a simple and robust in vitro strategy for prediction of human acute systemic toxicity, which could replace animal tests used for regulatory purposes. Our group is responsible for the characterization of the effect of the reference chemicals on the hematopoietic tissue. CFU-GM assay based on the culture of human mononuclear cord blood cells has been used to characterize the effects of the selected compounds on the myeloid progenitors. Previous results have shown the relevance of the CFU-GM assay for the prediction of human acute neutropenia after treatment of antitumoral compounds, and this assay has been recently approved by the ECVAM's Scientific Advisory Committee. Among the compounds included in the study there were pharmaceuticals, environmental pollutants and industrial chemicals. Eleven out of 55 chemicals did not show any cytotoxic effect at the maximum concentration tested. The correlation coefficients of CFU-GM IC50, IC70 and IC90 values with human LC50 values (50% lethal concentration calculated from time-related sublethal and lethal human blood concentrations) were 0.4965, 0.5106 and 0.5142 respectively. Although this correlation is not improve respect to classical in vitro basal cytotoxicity tests such as 3T3 Neutral Red Uptake, chemicals which deviate substantially in the correlation with these assays (colchicine, digoxin, 5-Fluorouracil and thallium sulfate) fitted very well in the linear regression analysis of the CFU-GM progenitors. The results shown in the present study indicate that the sensitivity of CFU-GM progenitors correlates better than the sensitivity of HL-60 cells with human LC50 values and could help to refine the predictability for human acute systemic toxicity when a given chemical may affect to the hematopoietic myeloid system.

  1. Effects of copy center particles on the lungs: A toxicological characterization using a Balb/c mice model

    PubMed Central

    Pirela, Sandra; Molina, Ramon; Watson, Christa; Cohen, Joel; Bello, Dhimiter; Demokritou, Philip; Brain, Joseph

    2015-01-01

    Context Printers and photocopiers release respirable particles into the air. Engineered nanomaterials (ENMs) have been recently incorporated into toner formulations but their potential toxicological effects have not been well studied. Objective To evaluate the biologic responses to copier-emitted particles in the lungs using a mouse model. Methods Particles from a university copy center were sampled and fractionated into three distinct sizes, two of which (PM0.1 and PM0.1–2.5) were evaluated in this study. The particles were extracted and dispersed in deionized water and RPMI/10% FBS. Hydrodynamic diameter and zeta potential were evaluated by dynamic light scattering. The toxicologic potential of these particles was studied using 8-week-old male Balb/c mice. Mice were intratracheally instilled with 0.2, 0.6, 2.0 mg/kg bw of the PM0.1 and PM0.1–2.5 size fractions. Fe2O3 and welding fumes were used as comparative materials, while RPMI/10% FBS was used as the vehicle control. Bronchoalveolar lavage (BAL) was performed 24 hours post-instillation. The BAL fluid was analyzed for total and differential cell counts, and biochemical markers of injury and inflammation. Results Particle size- and dose-dependent pulmonary effects were found. Specifically, mice instilled with PM0.1 (2.0 mg/kg bw) had significant increases in neutrophil number, lactate dehydrogenase and albumin compared to vehicle control. Likewise, pro-inflammatory cytokines were elevated in mice exposed to PM0.1 (2.0 mg/kg bw) compared to other groups. Conclusion Our results indicate that exposure to copier-emitted nanoparticles may induce lung injury and inflammation. Further exposure assessment and toxicological investigations are necessary to address this emerging environmental health pollutant. PMID:23895351

  2. A critical review of the toxicological effects of carrageenan and processed eucheuma seaweed on the gastrointestinal tract.

    PubMed

    Cohen, Samuel M; Ito, Nobuyuki

    2002-09-01

    Carrageenan is a high-molecular-weight, strongly anionic polymer derived from several species of red seaweed that is used for the textural stabilization of foods. Processed Eucheuma Seaweed (PES) is a form of carrageenan with a higher cellulose content. Food-grade carrageenan has a weight average molecular weight greater than 100,000 Da, with a low percentage of smaller fragments. Carrageenan is not degraded to any extent in the gastrointestinal tract and is not absorbed from it in species examined, such as rodents, dogs, and non-human primates. Systemically administered carrageenan has been reported to have a variety of effects, particularly on the immune system, but these are not pertinent to orally administered carrageenan. The substance poligeenan (formerly referred to as degraded carrageenan) is not a food additive. It exhibits toxicological properties at high doses that do not occur with the food additive carrageenan. In-long term bioassays, carrageenan has not been found to be carcinogenic, and there is no credible evidence supporting a carcinogenic effect or a tumor-promoting effect on the colon in rodents. Also, like many dietary fibers, there is significant cecal enlargement in rodents when it is administered at high doses, but this does not appear to be associated with any toxicological consequences to the rodent. Many toxicological studies on carrageenan have involved administration at doses in excess of today's standards for dietary feeding levels in bioassays, and they are orders of magnitude in excess of those to which humans are exposed. Previous reviews of carrageenan and PES by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) have recommended a group allowable daily intake (ADI) of "not specified". The lack of carcinogenic, genotoxic, or tumor-promoting activity with carrageenan strongly supports continuing such an ADI, and JECFA, during its most recent review in 2001, continued this

  3. How closely do acute lethal concentration estimates predict effects of toxicants on populations?

    PubMed

    Stark, John D

    2005-04-01

    Acute lethal dose/concentration estimates are the most widely used measure of toxicity and these data often are used in ecological risk assessment. However, the value of the lethal concentration (LC50) as a toxicological endpoint for use in ecological risk assessment recently has been criticized. A question that has been asked frequently is how accurate is the LC50 for prediction of longer-term effects of toxicants on populations of organisms? To answer this question, Daphnia pulex populations were exposed to nominal concentrations equal to the 48-h acute LC50 of 6 insecticides, Actara, Aphistar diazinon, pymetrozine, Neemix, and Spinosad; and 8 agricultural adjuvants, Bond, Kinetic, Plyac, R-11, Silwet, Sylgard 309, Water Maxx, and X-77; for 10 d. None of the D. pulex populations exposed to the acute LC50 of these insecticides were 50% lower than the control populations at the end of the study; exposure to diazinon resulted in populations that were higher than expected (91% of the control). Exposure to Actara and Aphistar resulted in populations that were < 1 and 29% of the control, respectively. Exposure to Fulfill, Neemix, and Spinosad resulted in extinction. Extinction occurred after exposure to all of the adjuvants, except Silwet L-77 where the population was 31% of the control. These results corroborate other studies that indicate that the LC50 is not a good predictor of effects on population growth. Although lethal concentration estimates have their place in toxicology, namely to compare intrinsic toxicity of chemicals among species or susceptibility of a species to different chemicals over short time periods, population growth and growth-rate studies are necessary to predict toxicant effects on populations.

  4. Antinociceptive and Toxicological Effects of Dioclea grandiflora Seed Pod in Mice

    PubMed Central

    Sá, Rita de Cássia da Silveira e; de Oliveira, Leandra Eugênia Gomes; de Farias Nóbrega, Franklin Ferreira; Bhattacharyya, Jnanabrata; de Almeida, Reinaldo Nóbrega

    2010-01-01

    The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice. PMID:20368784

  5. Acute Biphasic Effects of Ayahuasca.

    PubMed

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca's chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered. PMID:26421727

  6. Acute Biphasic Effects of Ayahuasca

    PubMed Central

    Schenberg, Eduardo Ekman; Alexandre, João Felipe Morel; Filev, Renato; Cravo, Andre Mascioli; Sato, João Ricardo; Muthukumaraswamy, Suresh D.; Yonamine, Maurício; Waguespack, Marian; Lomnicka, Izabela; Barker, Steven A.; da Silveira, Dartiu Xavier

    2015-01-01

    Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it's potential therapeutic effects is offered. PMID:26421727

  7. Effects of acute caffeine administration on adolescents.

    PubMed

    Temple, Jennifer L; Dewey, Amber M; Briatico, Laura N

    2010-12-01

    Acute caffeine administration has physiological, behavioral, and subjective effects. Despite its widespread use, few studies have described the impact of caffeine consumption in children and adolescents. The purpose of this study was to investigate the effects of acute caffeine administration in adolescents. We measured cardiovascular responses and snack food intake after acute administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared usual food intake and subjective effects of caffeine between high- and low-caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources and consumption levels. We found main effects of caffeine dose on heart rate (HR) and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with increasing caffeine dose. There were significant interactions among gender, caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks more than low consumers (<50 mg/day). Boys were more likely than girls to report using getting a rush, more energy, or improved athletic performance from caffeine. Finally, when we examined energy and macronutrient intake, we found that caffeine consumption was positively associated with laboratory energy intake, specifically from high-sugar, low-fat foods and also positively associated with protein and fat consumption outside of the laboratory. When taken together, these data suggest that acute caffeine administration has a broad range of effects in adolescents and that the magnitude of these effects is moderated by gender and chronic caffeine consumption. PMID:21186925

  8. The effect of some drugs on acute toxoplasmosis in mice.

    PubMed

    Hamadto, H H; Rashed, S M; Marii, N E; Sobhy, M M; el-Ridi, A M; el-Fakahany, A F

    1989-12-01

    The effect of some chemotherapeutics, on the course of acute toxoplasmosis in experimentally infected mice was studied. Obtained results showed that, praziquantel, levamisole had no effect on acute toxoplasmosis, while trimethoprim-sulphamethoxazole and clindamycin showed some prophylactic effect on acute toxoplasmosis in mice. PMID:2788673

  9. 20 years of toxicology.

    PubMed Central

    Fisher, B E

    1998-01-01

    With over 80,000 chemicals being used in commerce worldwide, it is important to identify the human health effects of these chemicals and the levels of exposure at which they are harmful to humans. In order to address this need, the National Toxicology Program (NTP) was established in 1978; since then, the NTP has become the world's leader in designing, conducting, and interpreting various types of toxicity assays. PMID:9755149

  10. Toxicologic studies of SRC materials

    SciTech Connect

    Mahlum, D.D.; Pelroy, R.A.; Drucker, H.; Wilson, B.W.; Massey, M.J.; Schmalzer, D.K.

    1980-02-01

    Investigations on the toxicity of SRC materials are reported. Toxicological studies include: microbial mutageneis (Ames test); in vitro mammalian cell toxicity and transformation assays; epidermal carcinogenesis (skin painting); acute and subchronic oral toxicity; developmental toxicity; dominant lethal assays; inhalation toxicity; and dosimetry and metabolism. The materials tested include: SRC-I process solvent, wash solvent, and light oil; SRC-II heavy distillate, middle distillate, and light distillate; shale oil; crude petroleum; and pure carcinogens. (DC)

  11. Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System.

    PubMed

    Autrup, Herman; Barile, Frank A; Blaauboer, Bas J; Degen, Gisela H; Dekant, Wolfgang; Dietrich, Daniel; Domingo, Jose L; Gori, Gio Batta; Greim, Helmuth; Hengstler, Jan G; Kacew, Sam; Marquardt, Hans; Pelkonen, Olavi; Savolainen, Kai; Vermeulen, Nico P

    2015-07-01

    The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be subjected to the well-evaluated health risk characterization approach used for many years including adverse outcome pathways. Many of the points arguing for a specific approach for risk characterization of chemicals with hormonal activity are based on highly speculative conclusions. These conclusions are not well supported when evaluating the available information.

  12. Analysis of volatile combustion products and a study of their toxicological effects.

    NASA Technical Reports Server (NTRS)

    Seader, J. D.; Einhorn, I. N.; Drake, W. O.; Mihlfeith, C. M.

    1972-01-01

    An experimental program was conducted to study the thermochemical, flammability and toxicological characteristics of uncoated and coated polyisocyanurate foams. The coatings used were fluorinated copolymer and an intumescent material. Combustion and pyrolysis gases were analyzed by gas chromatography and mass spectrometry. The LD-50 and LD-100 tests were performed on Sprague-Dawley rats housed in an environmental chamber. The isocyanurate foam, fluorinated-copolymer-coated foam, and the intumescent-coated foam were found to have excellent flammability and insulation characteristics, although smoke development was substantial.

  13. Acute effects of meals, noise and nightwork.

    PubMed

    Smith, A; Miles, C

    1986-08-01

    An experimental study of the acute effects of meals, noise and nightwork showed that there was a post-meal impairment in detection of targets in a cognitive vigilance task. This was found both during the day and at night, although certain features of the results suggested that the day and night effects were not equivalent. Noise increased the number of false alarms but reduced the post-meal impairment in hit rate. Subjects with low levels of trait or state anxiety showed the greatest post-lunch impairments in performance, but this effect was reduced when the meal was eaten at night.

  14. Toxicological Benchmarks for Wildlife

    SciTech Connect

    Sample, B.E. Opresko, D.M. Suter, G.W.

    1993-01-01

    Ecological risks of environmental contaminants are evaluated by using a two-tiered process. In the first tier, a screening assessment is performed where concentrations of contaminants in the environment are compared to no observed adverse effects level (NOAEL)-based toxicological benchmarks. These benchmarks represent concentrations of chemicals (i.e., concentrations presumed to be nonhazardous to the biota) in environmental media (water, sediment, soil, food, etc.). While exceedance of these benchmarks does not indicate any particular level or type of risk, concentrations below the benchmarks should not result in significant effects. In practice, when contaminant concentrations in food or water resources are less than these toxicological benchmarks, the contaminants may be excluded from further consideration. However, if the concentration of a contaminant exceeds a benchmark, that contaminant should be retained as a contaminant of potential concern (COPC) and investigated further. The second tier in ecological risk assessment, the baseline ecological risk assessment, may use toxicological benchmarks as part of a weight-of-evidence approach (Suter 1993). Under this approach, based toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. Other sources of evidence include media toxicity tests, surveys of biota (abundance and diversity), measures of contaminant body burdens, and biomarkers. This report presents NOAEL- and lowest observed adverse effects level (LOAEL)-based toxicological benchmarks for assessment of effects of 85 chemicals on 9 representative mammalian wildlife species (short-tailed shrew, little brown bat, meadow vole, white-footed mouse, cottontail rabbit, mink, red fox, and whitetail deer) or 11 avian wildlife species (American robin, rough-winged swallow, American woodcock, wild turkey, belted kingfisher, great blue heron, barred owl, barn owl, Cooper's hawk, and red-tailed hawk

  15. Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

    2008-11-01

    The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

  16. Toxicological evaluation of lactase derived from recombinant Pichia pastoris.

    PubMed

    Zou, Shiying; He, Xiaoyun; Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system.

  17. Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

    PubMed Central

    Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

  18. Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects.

    PubMed

    Cittadini, Francesca; De Giovanni, Nadia; Alcalde, Mireia; Partemi, Sara; Carbone, Arnaldo; Campuzano, Oscar; Brugada, Ramon; Oliva, Antonio

    2015-01-01

    Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient. PMID:25399050

  19. Carbamate nerve agent prophylatics exhibit distinct toxicological effects in the zebrafish embryo model.

    PubMed

    Fischer, Audrey; Wolman, Marc; Granato, Michael; Parsons, Michael; McCallion, Andrew S; Proescher, Jody; English, Emily

    2015-01-01

    Pyridostigmine bromide (PB) is an FDA-approved drug for the treatment of myasthenia gravis and a prophylactic pre-treatment for organophosphate nerve agent poisoning. Current methods for evaluating nerve agent treatments include enzymatic studies and mammalian models. Rapid whole animal screening tools for assessing the effects of nerve agent pre-treatment and post-exposure drugs represent an underdeveloped area of research. We used zebrafish as a model for acute and chronic developmental exposure to PB and two related carbamate acetylcholinesterase (AChE) inhibitors, neostigmine bromide (NB) and physostigmine (PS). Lethal doses and gross morphological phenotypes resulting from exposure to sub-lethal doses of these compounds were determined. Quantitative analyses of motility impairment and AChE enzyme inhibition were used to determine optimal dosing conditions for evaluation of the effects of carbamate exposures on neuronal development; ~50% impairment of response to startle stimuli and >50% inhibition of AChE activity were observed at 80 mMPB, 20 mM NB and 0.1 mM PS. PB induced stunted somite length, but no other phenotypic effects were observed. In contrast, NB and PS induced more severe phenotypic morphological defects than PB as well as neurite outgrowth mislocalization. Additionally, NB induced mislocalization of nicotinic acetylcholine receptors, resulting in impaired synapse formation. Taken together, these data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of carbamates and demonstrate the utility of the zebrafish model for distinguishing subtle structure-based differential effects of AChE inhibitors, which include nerve agents, pesticides and drugs.

  20. Toxicological effects of the lipid regulator gemfibrozil in four aquatic systems.

    PubMed

    Zurita, Jorge L; Repetto, Guillermo; Jos, Angeles; Salguero, Manuel; López-Artíguez, Miguel; Cameán, Ana M

    2007-02-15

    Gemfibrozil is a lipid-regulating agent widely used in patients at risk of coronary disease. Pharmaceutical products, such as gemfibrozil, are found in municipal effluents and represent a major source of contamination. To date, there is little available information about the adverse effects of gemfibrozil in aquatic organisms. For this reason, the toxic effects were investigated using model systems from four trophic levels. The most sensitive system was the immobilization of Daphnia magna, with a non-observed adverse effect level of 30 microM and a mean effective concentration of 120 microM after 72 h, followed by the inhibition of bioluminescence of Vibrio fischeri, the hepatoma fish cell line PLHC-1 line and the inhibition of the growth of Chlorella vulgaris. Although protein content, neutral red uptake, methylthiazol metabolization and lysosomal function were reduced in PLHC-1 cells, stimulations were observed for lysosomal function, metallothionein levels and succinate dehydrogenase, glucose-6-phosphate dehydrogenase and acetylcholinesterase activities. No changes were observed in ethoxyresorufin-O-deethylase activity. The main morphological alterations were hydropic degeneration and loss of cells. Modulation studies on gemfibrozil toxicity were also carried out. General antioxidants and calcium chelators did not modify the toxicity of gemfibrozil, whereas a Fe(III) chelator, a membrane permeable sulphydryl-protecting compound and glutathione level modifying agents did change the toxicity. One of the possible mechanisms of gemfibrozil toxicity seems to be the binding to sulphydryl groups, including those of glutathione. According to the result, gemfibrozil should be classified as harmful to aquatic organisms. However, comparing the concentrations in water and the toxicity quantified in the assayed systems, gemfibrozil is not expected to represent acute risk to the aquatic biota. PMID:17169444

  1. Toxicological effects of the aquatic herbicide, fluridone, on male water mites (Hydrachnidiae: Arrenurus: Megaluracarus).

    PubMed

    Yi, Sandra A; Francis, Bettina M; Jarrell, Wesley M; Soucek, David J

    2011-01-01

    The acute toxicities for technical grade fluridone (Sonar™) and the commercial formulation of fluridone (Sonar®AS) were assessed for male water mites (Hydrachnidiae: Arrenurus: Megaluracarus). Signs of toxicity were evaluated by detection of locomotor dysfunction or death after exposure to concentrations of 100,000, 10,000, 1,000, and 100 μg/L of Sonar™ and 10,000, 5,000, 1,000, 100, and 10 μg/L of Sonar®AS in US EPA, moderately hard reconstituted water (MHRW). The median effective concentration (EC50) was 891 and 631 μg/L for Sonar™ at 48 and 96 h and less than 10 μg/L for Sonar®AS at 96 h. Increased duration of exposure to Sonar®AS from 48 to 96 h had a significant effect on increasing the rate of combined morbidity and mortality. At the lowest concentration of Sonar®AS tested, which is half the concentration allowed within 400 m of any functioning potable water intake for human usage, 40% of the mites were adversely affected at 48 h and 70% were affected after 96 h of exposure. This study demonstrates that Sonar®AS is 60-fold more toxic to water mites than the active ingredient alone. At currently acceptable application rates of 90-150 μg/L fluridone, the addition of ingredients classified as inert, as in Sonar®AS, result in an increased risk of adverse effects on populations of male water mites (Arrenurus: Megaluracarus) in aquatic ecosystems.

  2. [Acute tonsillopharyngitis: the effectiveness of topical therapy].

    PubMed

    Nosulya, E V; Kim, I A; Chernykh, N M; Karnoukhova, O A

    2015-01-01

    The objective of the present study was to evaluate the clinical effectiveness of a furasol sore throat gargle solution for the treatment of acute tonsillopharyngitis. Forty patients presenting with acute tonsillopharyngitis were allocated to two groups, 20 subjects in each, by means of independent sequential randomization. Prior to the onset of the treatment, all the patients were examined for determining the species composition of pharyngeal microflora with the use of an «AutoScan4 System» analyzer («Siemens», USA) and estimating the resistance to antibacterial preparations (by the disk diffusion method). All the participants of the study were prescribed antibacterial therapy. In the patients of group 1 (study group), the antibacterial treatment of acute tonsillopharyngitis was supplemented by a furasol sore throat gargle solution whereas those of group 2 (controls) were treated without topical therapy. The quantitative evaluation of the severity of manifestations of the disease before and after the treatment was based on a 5-point visual-analog scale. It was shown that systemic antibacterial therapy resulted in the consistent decrease of the frequency of occurrence of pathogenic and potentially pathogenic microflora in the patients comprising both groups. Treatment with a furasol sore throat gargle solution did not lead to the appearance of bacterial species alien to the oropharynx, nor was it accompanied by the impairment of resistance of its mucous membrane to the colonization by microorganisms. The results of the study give evidence of the well apparent regression of the subjective signs of tonsillopharyngitis and the inflammatory changes in the mucous membrane of the pharynx in the patients given the topical treatment in the form of a furasol sore throat gargle solution in addition to antibacterial therapy. It is concluded that a furasol sore throat gargle solution can be recommended for the introduction into the combined treatment of the patients

  3. Acute marijuana effects on human risk taking.

    PubMed

    Lane, Scott D; Cherek, Don R; Tcheremissine, Oleg V; Lieving, Lori M; Pietras, Cythia J

    2005-04-01

    Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Delta9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.

  4. Effects of the lipid regulator drug gemfibrozil: A toxicological and behavioral perspective.

    PubMed

    Henriques, Jorge F; Almeida, Ana Rita; Andrade, Thayres; Koba, Olga; Golovko, Oksana; Soares, Amadeu M V M; Oliveira, Miguel; Domingues, Inês

    2016-01-01

    Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox(®) (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often

  5. The toxicologic effects of the carbamate insecticide aldicarb in mammals: a review.

    PubMed

    Risher, J F; Mink, F L; Stara, J F

    1987-06-01

    Aldicarb, 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime, is an oxime carbamate insecticide manufactured by the Union Carbide Corporation and sold under the trade name Temik. It is a soil-applied systemic pesticide used against certain insects, mites, and nematodes, and is applied below the soil surface for absorption by plant roots. It is generally applied to the soil in the form of 5, 10, or 15% granules, and soil moisture is essential for the release of the toxicant. Uptake by plants is rapid. Aldicarb is currently registered for use on cotton, sugar beets, sugar cane (Louisiana only), potatoes, sweet potatoes, peanuts, oranges, pecans (Southeast only), dry beans, soybeans, and ornamental plants. Home and garden use is not permitted. Discovery of aldicarb and its oxidative sulfoxide and sulfone metabolites in well or ground water in Florida, Wisconsin, and New York, and accidental poisonings from ingesting contaminated watermelons and cucumbers in the South and West have spurred interest and concern about this pesticide. The primary mechanism of toxic action of aldicarb is cholinesterase inhibition. However, unlike the relatively irreversible anticholinesterase activity of the organophosphate pesticides, the carbamylation process which produces the anti-AChE action is quickly reversible. Aldicarb is readily absorbed through both the gut and the skin, but is rapidly metabolized and excreted in the urine almost completely within 24 hr. Although it is acutely toxic to humans and laboratory animals, aldicarb is not known to be carcinogenic, teratogenic, conclusively mutagenic, or to produce other long-term adverse health effects. In cases of accidental poisoning, the cholinergic symptoms have generally subsided within 6 hr, with no side effects or complications. PMID:3304999

  6. The toxicologic effects of the carbamate insecticide aldicarb in mammals: a review.

    PubMed Central

    Risher, J F; Mink, F L; Stara, J F

    1987-01-01

    Aldicarb, 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime, is an oxime carbamate insecticide manufactured by the Union Carbide Corporation and sold under the trade name Temik. It is a soil-applied systemic pesticide used against certain insects, mites, and nematodes, and is applied below the soil surface for absorption by plant roots. It is generally applied to the soil in the form of 5, 10, or 15% granules, and soil moisture is essential for the release of the toxicant. Uptake by plants is rapid. Aldicarb is currently registered for use on cotton, sugar beets, sugar cane (Louisiana only), potatoes, sweet potatoes, peanuts, oranges, pecans (Southeast only), dry beans, soybeans, and ornamental plants. Home and garden use is not permitted. Discovery of aldicarb and its oxidative sulfoxide and sulfone metabolites in well or ground water in Florida, Wisconsin, and New York, and accidental poisonings from ingesting contaminated watermelons and cucumbers in the South and West have spurred interest and concern about this pesticide. The primary mechanism of toxic action of aldicarb is cholinesterase inhibition. However, unlike the relatively irreversible anticholinesterase activity of the organophosphate pesticides, the carbamylation process which produces the anti-AChE action is quickly reversible. Aldicarb is readily absorbed through both the gut and the skin, but is rapidly metabolized and excreted in the urine almost completely within 24 hr. Although it is acutely toxic to humans and laboratory animals, aldicarb is not known to be carcinogenic, teratogenic, conclusively mutagenic, or to produce other long-term adverse health effects. In cases of accidental poisoning, the cholinergic symptoms have generally subsided within 6 hr, with no side effects or complications. PMID:3304999

  7. The toxicologic effects of the carbamate insecticide aldicarb in mammals: a review.

    PubMed

    Risher, J F; Mink, F L; Stara, J F

    1987-06-01

    Aldicarb, 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime, is an oxime carbamate insecticide manufactured by the Union Carbide Corporation and sold under the trade name Temik. It is a soil-applied systemic pesticide used against certain insects, mites, and nematodes, and is applied below the soil surface for absorption by plant roots. It is generally applied to the soil in the form of 5, 10, or 15% granules, and soil moisture is essential for the release of the toxicant. Uptake by plants is rapid. Aldicarb is currently registered for use on cotton, sugar beets, sugar cane (Louisiana only), potatoes, sweet potatoes, peanuts, oranges, pecans (Southeast only), dry beans, soybeans, and ornamental plants. Home and garden use is not permitted. Discovery of aldicarb and its oxidative sulfoxide and sulfone metabolites in well or ground water in Florida, Wisconsin, and New York, and accidental poisonings from ingesting contaminated watermelons and cucumbers in the South and West have spurred interest and concern about this pesticide. The primary mechanism of toxic action of aldicarb is cholinesterase inhibition. However, unlike the relatively irreversible anticholinesterase activity of the organophosphate pesticides, the carbamylation process which produces the anti-AChE action is quickly reversible. Aldicarb is readily absorbed through both the gut and the skin, but is rapidly metabolized and excreted in the urine almost completely within 24 hr. Although it is acutely toxic to humans and laboratory animals, aldicarb is not known to be carcinogenic, teratogenic, conclusively mutagenic, or to produce other long-term adverse health effects. In cases of accidental poisoning, the cholinergic symptoms have generally subsided within 6 hr, with no side effects or complications.

  8. The no-observed-adverse-effect level (NOAEL) of baby aloe powder (BAP) for nutraceutical application based upon toxicological evaluation.

    PubMed

    Kwack, Seung Jun; Do, Seon-Gil; Kim, Young Woo; Kim, Yeon-Joo; Gwak, Hyo-Min; Park, Hyun Jong; Roh, Taehyun; Shin, Min Kyung; Lim, Seong Kwang; Kim, Hyung Sik; Lee, Byung-Mu

    2014-01-01

    Aloe has been used in versatile herbal medications and nutraceuticals throughout history. Aloe is widely considered to be generally safe for humans and used globally. The effectiveness and pharmacological properties of aloe are dependent upon when the plant is collected. However, little is known about the toxicology of whole-body aloe collected within less than 1 yr. Based upon widespread exposure to aloe, it is important to determine a daily intake level of this chemical to ensure its safety for humans. To determine the no-observed-adverse-effect level (NOAEL) of baby aloe powder (BAP) for clinical application, Sprague-Dawley (SD) rats were treated orally for 4 wk with 4 different concentrations: 0, 0.125, 0.5, and 2 g/kg body weight (bw). In this study, no significant or dose-dependent toxicological effects of BAP were observed in biochemical or hematological parameters, urinalysis, clinical signs, body weight, and food and water consumption. There were changes in some biomarkers in certain treated groups compared to controls; however, all values were within their reference ranges and not dose-dependent. Based on these results, the NOAEL of BAP was estimated to be greater than 2 g/kg bw in male and 2 g/kg bw in female SD rats. Collectively, these data suggest that BAP used in this study did not produce any marked subacute toxic effects up to a maximum concentration of 2 g/kg bw, and thus use in nutraceuticals and in pharmaceutical and cosmetic applications at a concentration of >2 g/kg is warranted.

  9. The use of kestrels in toxicology

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Lincer, J.L.; Bird, David M.; Bowen, Reed

    1987-01-01

    Various species of kestrels have become important bioindicators of environmental quality and test species for comparative toxicology in captivity. At least 7 species of kestrels have been used to document the presence of environmental contamination primarily organochlorines and metals, in at least 15 countries. Captive kestrels have been used in studies involving a wide variety of environmental contaminants and toxicants examining: bioaccumulation; lethal toxicity using acute, chronic, and secondary exposures; effects on reproduction, eggshell thickness, and related enzyme systems; and effects on a wide variety of physiological and biochemical parameters. Field studies have examined the response of kestrels to exposure to insecticides. Kestrels should continue to play a vital role as a bioindicator and raptorial 'white mouse', especially because of their relationship to other falconiformes, several of which have been shown to be extremely sensitive to environmental changes.

  10. History of wildlife toxicology.

    PubMed

    Rattner, Barnett A

    2009-10-01

    The field of wildlife toxicology can be traced to the late nineteenth and early twentieth centuries. Initial reports included unintentional poisoning of birds from ingestion of spent lead shot and predator control agents, alkali poisoning of waterbirds, and die-offs from maritime oil spills. With the advent of synthetic pesticides in the 1930s and 1940s, effects of DDT and other pesticides were investigated in free-ranging and captive wildlife. In response to research findings in the US and UK, and the publication of Silent Spring in 1962, public debate on the hazards of pollutants arose and national contaminant monitoring programs were initiated. Shortly thereafter, population-level effects of DDT on raptorial and fish-eating birds were documented, and effects on other species (e.g., bats) were suspected. Realization of the global nature of organochlorine pesticide contamination, and the discovery of PCBs in environmental samples, launched long-range studies in birds and mammals. With the birth of ecotoxicology in 1969 and the establishment of the Society of Environmental Toxicology and Chemistry in 1979, an international infrastructure began to emerge. In the 1980s, heavy metal pollution related to mining and smelting, agrichemical practices and non-target effects, selenium toxicosis, and disasters such as Chernobyl and the Exxon Valdez dominated the field. Biomarker development, endocrine disruption, population modeling, and studies with amphibians and reptiles were major issues of the 1990s. With the turn of the century, there was interest in new and emerging compounds (pharmaceuticals, flame retardants, surfactants), and potential population-level effects of some compounds. Based upon its history, wildlife toxicology is driven by chemical use and misuse, ecological disasters, and pollution-related events affecting humans. Current challenges include the need to more thoroughly estimate and predict exposure and effects of chemical-related anthropogenic

  11. Biomarkers in Computational Toxicology

    EPA Science Inventory

    Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

  12. Toxicology Education Foundation

    MedlinePlus

    ... to Toxicology Excellence for Risk Assessment for website design. Donate Now OUR MISSION AND VISION Our mission is to enhance public understanding of toxicology through access to objective, science-based information on the safety of chemicals and other agents ...

  13. After-effects of acute alcohol intoxication.

    PubMed

    York, J L; Regan, S G

    1988-01-01

    Female, Long-Evans hooded rats (N = 10, 4 months of age) were given ethanol via intragastric intubation in doses of 2.0, 3.0 or 4.0 g/kg (repeated measures design). After-effects (hypothermia, free operant activity, motor performance) were measured at six, twelve and sixteen hours, respectively, for the above doses and were compared to the effects observed after the intubation of equivolume amounts of tap water. The after-effects of ethanol on rectal temperature were varied. Both rotarod performance and free operant activity were impaired after each of the above doses of ethanol. Blood ethanol analyses revealed low blood levels of ethanol (range 6.6 +/- 1.5 to 24.6 +/- 3.4 mg/100 ml) at the time behavioral tests were performed. Thus, quantifiable behavioral impairment was observed after blood ethanol values had declined following acute intoxication episodes. These changes may be related to "hangover" symptomatology in man and may serve as a model for investigating the influence of a variety of factors related to drug dosage, rate of ethanol ingestion, type of alcoholic beverage, and prophylactic or acute intervention therapeutics.

  14. Toxicological approaches to complex mixtures.

    PubMed Central

    Mauderly, J L

    1993-01-01

    This paper reviews the role of toxicological studies in understanding the health effects of environmental exposures to mixtures. The approach taken is to review mixtures that have received the greatest emphasis from toxicology; major mixtures research programs; the toxicologist's view of mixtures and approaches to their study; and the complementary roles of toxicological, clinical, and epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion products, and air pollutants comprise most of the past research on mixtures. Because of their great experimental control over subjects, exposures, and endpoints, toxicologists tend to consider a wider range of toxic interactions among mixture components and sequential exposures than is practical for human studies. The three fundamental experimental approaches used by toxicologists are integrative (studying the mixture as a whole), dissective (dissecting a mixture to determine causative constituents), and synthetic (studying interactions between agents in simple combinations). Toxicology provides information on potential hazards, mechanisms by which mixture constituents interact to cause effects, and exposure dose-effect relationships; but extrapolation from laboratory data to quantitative human health risks is problematic. Toxicological, clinical, and epidemiological approaches are complementary but are seldom coordinated. Fostering synergistic interactions among the disciplines in studying the risks from mixtures could be advantageous. PMID:7515806

  15. Toxicological approaches to complex mixtures.

    PubMed

    Mauderly, J L

    1993-12-01

    This paper reviews the role of toxicological studies in understanding the health effects of environmental exposures to mixtures. The approach taken is to review mixtures that have received the greatest emphasis from toxicology; major mixtures research programs; the toxicologist's view of mixtures and approaches to their study; and the complementary roles of toxicological, clinical, and epidemiological studies. Studies of tobacco smoke, engine exhaust, combustion products, and air pollutants comprise most of the past research on mixtures. Because of their great experimental control over subjects, exposures, and endpoints, toxicologists tend to consider a wider range of toxic interactions among mixture components and sequential exposures than is practical for human studies. The three fundamental experimental approaches used by toxicologists are integrative (studying the mixture as a whole), dissective (dissecting a mixture to determine causative constituents), and synthetic (studying interactions between agents in simple combinations). Toxicology provides information on potential hazards, mechanisms by which mixture constituents interact to cause effects, and exposure dose-effect relationships; but extrapolation from laboratory data to quantitative human health risks is problematic. Toxicological, clinical, and epidemiological approaches are complementary but are seldom coordinated. Fostering synergistic interactions among the disciplines in studying the risks from mixtures could be advantageous.

  16. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR CHLOROETHANE

    EPA Science Inventory

    Toxicological data in the published literature on Chloroethane (CE) will be assimilated, reviewed, and integated into a Toxicological Review of CE (assessment document), which seeks to characterize the key cancer, and non cancer health effect hazards from environmental exposures...

  17. The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

    EPA Science Inventory

    Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

  18. Principals Of Radiation Toxicology: Important Aspects.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    “All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al

  19. Effect of fuel zinc content on toxicological responses of particulate matter from pellet combustion in vitro.

    PubMed

    Uski, O; Jalava, P I; Happo, M S; Torvela, T; Leskinen, J; Mäki-Paakkanen, J; Tissari, J; Sippula, O; Lamberg, H; Jokiniemi, J; Hirvonen, M-R

    2015-04-01

    Significant amounts of transition metals such as zinc, cadmium and copper can become enriched in the fine particle fraction during biomass combustion with Zn being one of the most abundant transition metals in wood combustion. These metals may have an important role in the toxicological properties of particulate matter (PM). Indeed, many epidemiological studies have found associations between mortality and PM Zn content. The role of Zn toxicity on combustion PM was investigated. Pellets enriched with 170, 480 and 2300 mg Zn/kg of fuel were manufactured. Emission samples were generated using a pellet boiler and the four types of PM samples; native, Zn-low, Zn-medium and Zn-high were collected with an impactor from diluted flue gas. The RAW 264.7 macrophage cell line was exposed for 24h to different doses (15, 50,150 and 300 μg ml(-1)) of the emission samples to investigate their ability to cause cytotoxicity, to generate reactive oxygen species (ROS), to altering the cell cycle and to trigger genotoxicity as well as to promote inflammation. Zn enriched pellets combusted in a pellet boiler produced emission PM containing ZnO. Even the Zn-low sample caused extensive cell cycle arrest and there was massive cell death of RAW 264.7 macrophages at the two highest PM doses. Moreover, only the Zn-enriched emission samples induced a dose dependent ROS response in the exposed cells. Inflammatory responses were at a low level but macrophage inflammatory protein 2 reached a statistically significant level after exposure of RAW 264.7 macrophages to ZnO containing emission particles. ZnO content of the samples was associated with significant toxicity in almost all measured endpoints. Thus, ZnO may be a key component producing toxicological responses in the PM emissions from efficient wood combustion. Zn as well as the other transition metals, may contribute a significant amount to the ROS responses evoked by ambient PM. PMID:25553547

  20. Potential health effects of gasoline and its constituents: A review of current literature (1990-1997) on toxicological data.

    PubMed Central

    Caprino, L; Togna, G I

    1998-01-01

    We reviewed toxicological studies, both experimental and epidemiological, that appeared in international literature in the period 1990-1997 and included both leaded and unleaded gasolines as well as their components and additives. The aim of this overview was to select, arrange, and present references of scientific papers published during the period under consideration and to summarize the data in order to give a comprehensive picture of the results of toxicological studies performed in laboratory animals (including carcinogenic, teratogenic, or embryotoxic activity), mutagenicity and genotoxic aspects in mammalian and bacterial systems, and epidemiological results obtained in humans in relation to gasoline exposure. This paper draws attention to the inherent difficulties in assessing with precision any potential adverse effects on health, that is, the risk of possible damage to man and his environment from gasoline. The difficulty of risk assessment still exists despite the fact that the studies examined are definitely more technically valid than those of earlier years. The uncertainty in overall risk determination from gasoline exposure also derives from the conflicting results of different studies, from the lack of a correct scientific approach in some studies, from the variable characteristics of the different gasoline mixtures, and from the difficulties of correctly handling potentially confounding variables related to lifestyle (e.g., cigarette smoking, drug use) or to preexisting pathological conditions. In this respect, this paper highlights the need for accurately assessing the conclusive explanations reported in scientific papers so as to avoid the spread of inaccurate or misleading information on gasoline toxicity in nonscientific papers and in mass-media messages. PMID:9452413

  1. Oleoresin Capsicum toxicology evaluation and hazard review

    SciTech Connect

    Archuleta, M.M.

    1995-10-01

    Oleoresin Capsicum (OC) is an extract of the pepper plant used for centuries as a culinary spice (hot peppers). This material has been identified as a safe and effective Less-Than- Lethal weapon for use by Law enforcement and security professionals against assault. The National Institute of Justice (NIJ) is currently also evaluating its use in conjunction with other Less-Than-Lethal agents such as aqueous foam for use in corrections applications. Therefore, a comprehensive toxicological review of the literature was performed for the National Institute of Justice Less-Than-Lethal Force program to review and update the information available on the toxicity and adverse health effects associated with OC exposure. The results of this evaluation indicate that exposure to OC can result in dermatitis, as well as adverse nasal, pulmonary, and gastrointestinal effects in humans. The primary effects of OC exposure include pain and irritation of the mucous membranes of the eyes, nose, and lining of the mouth. Blistering and rash have been shown to occur after chronic or prolonged dermal exposure. Ingestion of capsicum may cause acute stinging of the lips, tongue, and oral mucosa and may lead to vomiting and diarrhea with large doses. OC vapors may also cause significant pulmonary irritation and prolonged cough. There is no evidence of long term effects associated with an acute exposure to OC, and extensive use as a culinary additive and medicinal ointment has further provided no evidence of long term adverse effects following repeated or prolonged exposure.

  2. Acute toxic effects of fragrance products.

    PubMed

    Anderson, R C; Anderson, J H

    1998-01-01

    To evaluate whether fragrance products can produce acute toxic effects in mammals, we allowed groups of male Swiss-Webster mice to breathe the emissions of five commercial colognes or toilet water for 1 h. We used the ASTM-E-981 test method to evaluate sensory irritation and pulmonary irritation. We used a computerized version of this test to measure the duration of the break at the end of inspiration and the duration of the pause at the end of expiration. Decreases in expiratory flow velocity indicated airflow limitation. We subjected the mice to a functional observational battery to probe for changes in nervous system function. The emissions of these fragrance products caused various combinations of sensory irritation, pulmonary irritation, decreases in expiratory airflow velocity, as well as alterations of the functional observational battery indicative of neurotoxicity. Neurotoxicity was more severe after mice were repeatedly exposed to the fragrance products. Evaluation of one of the test atmospheres with gas chromatography/mass spectrometry revealed the presence of chemicals for which irritant and neurotoxic properties had been documented previously. In summary, some fragrance products emitted chemicals that caused a variety of acute toxicities in mice.

  3. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  4. Toxicological effects and recovery of the corneal epithelium in Cyprinus carpio communis Linn. exposed to monocrotophos: an scanning electron microscope study.

    PubMed

    Uppal, Ravneet Kaur; Johal, Mohinder Singh; Sharma, Madan Lal

    2015-05-01

    This study was conducted based on the evidence of fish habitats in North India being affected by organophosphate pesticides draining from agricultural fields into bodies of water, especially during the rainy season. Various tissues of fish such as scales, gills ovaries, kidney, and liver have been studied from the toxicological point of view, but the toxicological effects of aquatic pollutants on fish cornea have not been investigated to date. We conducted comparative toxicological studies on the cornea of Cyprinus carpio communis using two sublethal (0.038 and 0.126 ppm) concentrations of monocrotophos pesticide for 30 days. Corneas from all the groups were evaluated by a scanning electron microscope. The fish exposed to the monocrotophos pesticide developed corneal necrosis due to the formation of crystalloid-like structures, thinning and shrinkage of microridges on the corneal epithelium. After 30 days, fish from the monocrotophos-treated tank were transferred to normal environmental conditions. After 60 days under natural condition, epithelial cells did not fully recover. In conclusion, exposure to monocrotophos induces irreversible changes in the cornea of C. carpio communis. As fish and mammalian visual systems share many similarities, the reported finding may offer useful insights for further toxicological and ophthalmological studies in humans.

  5. Organic acids and bases: Review of toxicological studies

    SciTech Connect

    Leung, H.W.; Paustenbach, D.J. )

    1990-01-01

    Organic acids and bases are among the most frequently used chemicals in the manufacturing industries. However, the toxicology of only a number of them has been fully characterized, and for fewer still have occupational exposure limits been established. This paper reviews the acute and chronic toxicity data of the organic acids and bases, and considers the mechanism by which these chemicals produce their effects. A methodology for establishing preliminary occupational exposure limits based on the physicochemical properties of these chemicals is presented. Workplace exposure limits for 20 organic acids and bases which currently have no exposure guidelines are suggested. Advice regarding appropriate medical treatment of exposure to these materials is discussed. 98 references.

  6. Nanotechnology: Toxicologic Pathology

    PubMed Central

    Hubbs, Ann F.; Sargent, Linda M.; Porter, Dale W.; Sager, Tina M.; Chen, Bean T.; Frazer, David G.; Castranova, Vincent; Sriram, Krishnan; Nurkiewicz, Timothy R.; Reynolds, Steven H.; Battelli, Lori A.; Schwegler-Berry, Diane; McKinney, Walter; Fluharty, Kara L.; Mercer, Robert R.

    2015-01-01

    Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. PMID:23389777

  7. Eco-toxicological effects of two kinds of lead compounds on forest tree seed in alkaline soil.

    PubMed

    Yang, Nan; Zhou, Fu-Rong; Wang, Jin-Xin

    2016-03-01

    In order to compare the different eco-toxicological effects of lead nitrate and lead acetate on forest tree seed, a biological incubation experiment was conducted to testify the inhibition effects of two lead compounds on rates of seed germination, root and stem elongation, and seedling fresh weight for six plants (Amaorpha fruticosa L., Robinia psedoacacia L., Pinus tabuliformis Carr., Platycladus orientalis L., Koelreuteria paniculata Laxm., Hippophae rhamnoides L.) in soil. The results indicate that the inhibition effects of the two lead compounds on the rates of root elongation of plants were greater than other indices; root elongation can possibly be used as indices to investigate the relationship between lead toxicity and plant response. The response of trees to lead toxicity varied significantly, and the order of tolerance to lead pollution was as follows: Amaorpha fruticosa L. > Platycladus orientalis L. > Koelreuteria paniculata Laxm. > Robinia psedoacacia L. > Pinus tabuliformis Carr. > Hippophae rhamnoides L. Therefore, we suggest that Amaorpha fruticosa L. and Platycladus orientalis L. be used as tolerant plants for soil phytoremediation and Hippophae rhamnoides L. as an indicative plant to diagnose the toxicity of lead pollution on soil quality. Lead nitrate and lead acetate differentially restrain seeds, with seeds being more sensitive to lead nitrate than lead acetate in the soil. Thus, the characteristics of lead compounds should be taken into full consideration to appraise its impact on the environment.

  8. Do recent data from the Seychelles Islands alter the conclusions of the NRC Report on the toxicological effects of methylmercury?

    PubMed

    Stern, Alan H; Jacobson, Joseph L; Ryan, Louise; Burke, Thomas A

    2004-01-30

    In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to the release of the most recent longitudinal update of the Seychelles Island study. It has recently been posited that these findings supercede those of the NRC committee, and that based on the Seychelles findings, there is little or no risk of adverse neurodevelopmental effects at current levels of exposure. In this commentary, members of the NRC committee address the conclusions from the NRC report in light of the recent Seychelles data. We conclude that no evidence has emerged since the publication of the NRC report that alters the findings of that report. PMID:14754462

  9. Toxicological in vitro effects of heavy metals on gilthead seabream (Sparus aurata L.) head-kidney leucocytes.

    PubMed

    Morcillo, Patricia; Cordero, Héctor; Meseguer, José; Esteban, María Á; Cuesta, Alberto

    2015-12-25

    Heavy metals provoke toxicological effects on aquatic animal species, including fish, though their effects on fish leucocytes and immunotoxicology are still limited. In the present work the effects of heavy metals (Cd, Hg, Pb or As) on viability, oxidative stress and innate immune parameters of isolated head-kidney leucocytes from gilthead seabream (Sparus aurata) are studied. Cytotoxicity results indicated that short exposures (30 min or 2h) to Hg promoted both apoptosis and necrosis cell death of leucocytes whilst Cd, Pb and As did only by apoptosis, in all cases in a concentration- and time-dependent manner. In addition, production of free oxygen radicals was induced by Cd, Hg and As heavy metals. Cd failed to change phagocytosis but Hg and As increased the percentage of phagocytic cells but decreased the number of ingested particles per cell whilst Pb increased both phagocytic parameters. On the other hand, respiratory burst activity was significantly reduced by incubation with Cd, Hg and As but increased with Pb. Furthermore, the gene expression profiles partly support the functional finding of this work. This study provides an in vitro approach for elucidating the heavy metals toxicity, and particularly the immunotoxicity, in fish leucocytes.

  10. Eco-toxicological effects of two kinds of lead compounds on forest tree seed in alkaline soil.

    PubMed

    Yang, Nan; Zhou, Fu-Rong; Wang, Jin-Xin

    2016-03-01

    In order to compare the different eco-toxicological effects of lead nitrate and lead acetate on forest tree seed, a biological incubation experiment was conducted to testify the inhibition effects of two lead compounds on rates of seed germination, root and stem elongation, and seedling fresh weight for six plants (Amaorpha fruticosa L., Robinia psedoacacia L., Pinus tabuliformis Carr., Platycladus orientalis L., Koelreuteria paniculata Laxm., Hippophae rhamnoides L.) in soil. The results indicate that the inhibition effects of the two lead compounds on the rates of root elongation of plants were greater than other indices; root elongation can possibly be used as indices to investigate the relationship between lead toxicity and plant response. The response of trees to lead toxicity varied significantly, and the order of tolerance to lead pollution was as follows: Amaorpha fruticosa L. > Platycladus orientalis L. > Koelreuteria paniculata Laxm. > Robinia psedoacacia L. > Pinus tabuliformis Carr. > Hippophae rhamnoides L. Therefore, we suggest that Amaorpha fruticosa L. and Platycladus orientalis L. be used as tolerant plants for soil phytoremediation and Hippophae rhamnoides L. as an indicative plant to diagnose the toxicity of lead pollution on soil quality. Lead nitrate and lead acetate differentially restrain seeds, with seeds being more sensitive to lead nitrate than lead acetate in the soil. Thus, the characteristics of lead compounds should be taken into full consideration to appraise its impact on the environment. PMID:26927657

  11. Effects of planting system design on the toxicological sensitivity of Myriophyllum spicatum and Elodea canadensis to atrazine.

    PubMed

    McGregor, Erin B; Solomon, K R; Hanson, M L

    2008-09-01

    The triazine herbicide atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-trazine) was selected as a chemical stressor in an investigation of how toxicological responses of individually grown macrophytes reflect those of plants grown in more natural model populations and two-species communities. Phytotoxicity of the compound to Myriophyllumspicatum L. and Elodeacanadensis Michx. was assessed under semi-natural field conditions using 12000l outdoor microcosms. Exposure concentrations of 25, 50, 100, 250microgl(-1) plus controls (n=3) were evaluated, selected to fall within a range of concentrations known to produce a toxic response in the tested macrophytes, and effective concentrations required to cause a decrease in biomass endpoints by 10%, 25%, and 50% were estimated. The sensitivities of aquatic plants to atrazine did not differ substantially between planting systems, and few interactions between the effects of the planting method and atrazine effects on macrophyte biomass were detected using a two-way ANOVA. A lack of significant differences in biomass and relative growth rate measures between plants grown under the various test systems also indicated that interactions between and among species did not influence growth of plants in the model population and communities. Under these test conditions, the use of the "cone-tainer" method provided estimates of toxicity consistent with those from plants grown in assemblages, and potential interactions between plants were not found to modify the response of macrophytes to atrazine.

  12. Aquatic toxicology: fact or fiction

    SciTech Connect

    Macek, K.J.

    1980-02-01

    The science of aquatic toxicology is a relatively new science. The development of the field of aquatic toxicology since 1930 is traced. The state of the art of aquatic toxicology compared with that of classical toxicology is evaluated. The science of aquatic toxicology is expected to undergo a significant period of rapid growth and development, leading ultimately to the formation of a mature science.

  13. Toxicological Effects Induced by Silver Nanoparticles in Zebra Fish (Danio Rerio) and in the Bacteria Communities Living at Their Surface.

    PubMed

    Bacchetta, Carla; López, Gerardo; Pagano, Gisela; Muratt, Diana Tomazi; de Carvalho, Leandro Machado; Monserrat, José María

    2016-10-01

    The antimicrobial activity of silver nanoparticles (AgNP) makes them useful in a wide range of products although their environmental impact is still uncertain. The main goal of this study was to evaluate short-term effects induced by AgNP on gills oxidative status and bacterial communities living at the skin mucus of zebrafish. Both the number of bacteria colony forming units and bacteria growth obtained from skin mucus were lower in all concentrations tested (25, 50 and 100 µg nAg/L). Besides, AgNP exposure caused a significant decrease in bacteria growth in zebrafish exposed to 100 µg nAg/L. AgNP accumulated in zebrafish gills at both highest concentrations tested, but this accumulation did not appear to result in oxidative stress. Overall the results indicated toxicological effects of AgNP on bacteria communities living at the zebrafish mucus surface. Although silver accumulation was verified in gills, no evidence of toxicity in terms of oxidative stress was found.

  14. Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects

    PubMed Central

    Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

    2016-01-01

    Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

  15. Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects.

    PubMed

    Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

    2016-04-01

    Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

  16. Toxicological effects of multi-walled carbon nanotubes on Saccharomyces cerevisiae: The uptake kinetics and mechanisms and the toxic responses.

    PubMed

    Zhu, Song; Zhu, Bin; Huang, Aiguo; Hu, Yang; Wang, Gaoxue; Ling, Fei

    2016-11-15

    Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of oxidized multi-walled carbon nanotubes (MWCNTs) were investigated following exposure to 0-600mg/L for 24h. Results indicated that MWCNTs (>100mg/L) had adverse effects on the cell proliferation. MWCNTs were clearly visible in lysosome, vacuole, endosome, mitochondria, multivesicular body and localization in the perinuclear region. The uptake kinetics data demonstrated that the maximum MWCNTs content (209.61mg/g) was reached at 3h, and a steady state was reached after 18h. Based on the combined results of transmission electron microscope, endocytosis inhibition experiments and endocytosis-related genes (END3, END6, Sla2 and Rsp5) expression analysis, we elucidated MWCNTs uptake mechanism: (i) via a direct penetration of single MWCNTs; (ii) via endocytosis of single MWCNTs; and (iii) via endocytosis of MWCNTs aggregates. The percentage of apoptosis was significant increased at 600mg/L. The decrease of mitochondrial transmembrane potential and the leakage of cytochrome c shown dose-dependent manners. Interestingly, there was no significant increase of reactive oxygen species (ROS). The apoptosis-related genes (SOD1, SOD2, Yca1, Nma111 and Nuc1) were significant changed. These results obtained in our study demonstrated that oxidized MWCNTs induce Saccharomyces cerevisiae apoptosis via mitochondrial impairment pathway. PMID:27475463

  17. Toxicological Effects Induced by Silver Nanoparticles in Zebra Fish (Danio Rerio) and in the Bacteria Communities Living at Their Surface.

    PubMed

    Bacchetta, Carla; López, Gerardo; Pagano, Gisela; Muratt, Diana Tomazi; de Carvalho, Leandro Machado; Monserrat, José María

    2016-10-01

    The antimicrobial activity of silver nanoparticles (AgNP) makes them useful in a wide range of products although their environmental impact is still uncertain. The main goal of this study was to evaluate short-term effects induced by AgNP on gills oxidative status and bacterial communities living at the skin mucus of zebrafish. Both the number of bacteria colony forming units and bacteria growth obtained from skin mucus were lower in all concentrations tested (25, 50 and 100 µg nAg/L). Besides, AgNP exposure caused a significant decrease in bacteria growth in zebrafish exposed to 100 µg nAg/L. AgNP accumulated in zebrafish gills at both highest concentrations tested, but this accumulation did not appear to result in oxidative stress. Overall the results indicated toxicological effects of AgNP on bacteria communities living at the zebrafish mucus surface. Although silver accumulation was verified in gills, no evidence of toxicity in terms of oxidative stress was found. PMID:27393328

  18. Toxicological evaluation of the effects of waste-to-energy ash-concrete on two marine species

    SciTech Connect

    Hamilton, K.L.; Nelson, W.G.; Curley, J.L. )

    1993-10-01

    The toxicological effects of waste-to-energy ash-concrete on survivorship, growth, and fecundity (end-point parameters) of Mysidopsis bahia and on survivorship and growth of Menidia beryllina were evaluated with the 7-d static-renewal toxicity test. Leachate and elutriate solutions were prepared from experimental ash-concrete test cylinders constructed from concrete with additions of either bottom ash (mix BA), mixed bottom ash and scrubber residue, or mixed bottom ash and fly ash (60:40%, mix BA:FA). Control experiments with concrete (without ash) and pH (7-9.5) were conducted to assess any toxic effects of the stabilization process. pH did not affect end-point parameters of Mysidopsis bahia or Menidia beryllina. However, the 100% elutriate solution made from concrete reduced survivorship of Mysidopsis bahia. For experiments with ash-concrete test cylinders with the BA mixture, 10-d leachate solution reduced survivorship of Mysidopsis bahia and the 100% elutriate solutions reduced survivorship of Mysidopsis bahia and Manidia beryllina. With the BA:SR mixture, the 100 and 50% elutriate solutions reduced survivorship of Menidia beryllina. The BA:FA 10- and 5-d leachate solutions and the 100, 50, and 25% elutriate solutions reduced survivorship of Menidia beryllina. The BA:FA 10- and 5-d leachate solutions and the 100, 50, 25% elutriate solutions reduced survivorship of Mysidopsis bahia.

  19. Proteomic and metabolomic analysis on the toxicological effects of As (III) and As (V) in juvenile mussel Mytilus galloprovincialis.

    PubMed

    Yu, Deliang; Ji, Chenglong; Zhao, Jianmin; Wu, Huifeng

    2016-05-01

    Inorganic arsenic (As) is a known pollutant including two chemical forms (arsenite (As III) and arsenate (As V)), in marine and coastal environment. Marine mussel Mytilus galloprovincialis is an important environmental monitoring species around the world. In this study, we focused on valence-specific responses of As in juvenile mussel M. galloprovincialis using a combined proteomic and metabolomic approach. Metabolic responses indicated that As (III) mainly caused disturbance in osmotic regulation in juvenile mussels. As (V) caused disturbances in both osmotic regulation and energy metabolism marked by different metabolic responses, including betaine, taurine, glucose and glycogen. Proteomic responses exhibited that As (III) had a significant negative effect on cytoskeleton and cell structure (actin and collagen alpha-6(VI) chain). As (V) affected some key enzymes involved in energy metabolism (cytosolic malate dehydrogenase, cMDH) and cell development (ornithine aminotransferase and astacin). Overall, all these results confirmed the valence-specific responses in juvenile mussels to As exposures. These findings demonstrate that a combined metabolomic and proteomic approach could provide an important insight into the toxicological effects of environmental pollutants in organisms.

  20. Microbiology & Toxicology: Space Environment

    NASA Video Gallery

    One key aspect in maintaining crew health and performance during spaceflight missions is the provision of a habitable environment with acceptably low concentrations of microbiological and toxicolog...

  1. [Toxicologic estimation, an element of therapeutical progress].

    PubMed

    Fournier, P E

    1991-01-01

    The clinical toxicology plays a great part to the progresses of human therapy. It is an essential observation for a good clinical use of drugs and of materials used by physicians. It permits a better knowledge of the dose-effect relationship (in acute either in chronic adverse effects). It specifies the statement of the therapeutic efficacy between the threshold, a placebo effect with adverse disorders as those possibly related to any xenobiotic and the overdose where the nocivity predominates on the therapeutic results. A better detection of some individual responses as adverse or toxic reactions due to a genetic peculiarity belongs to clinical toxicogenetic studies in parallel with pharmacogenetics. The recent evolution of drugs needs a more scientific approach of the therapy for cytotoxic drugs largely used against cancers, in terms of tolerable doses, cumulative actions, interactions and cofactors. On the opposite, the bio-chemical variations of new bio-drugs acting as real bioprotheses of hormones or biomediators need specific toxicological studies according to the progresses and to the limits of biotechnologies. Among numerous drugs issued of chemical research one must separate the reversible functional drugs designed as enzyme-inhibitors or cellular receptors ligands very close to the dominant themes of biochemistry and experimental physiology from chemicals coined by synthetic "chance" which are for the time being plain xenobiotics whose dangers are often poorly evaluated but whose practical applications will take place either in disciplines related to pharmacopea like chemicals used in plant protection, either beginning their commercial trip very far from health concern in industrial preparations and being brought back to medicine as plastics, glues or metallic implants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1842171

  2. Educational Challenges in Toxicology.

    ERIC Educational Resources Information Center

    Dixon, Robert L.

    1984-01-01

    Issues and topics related to educational challenges in toxicology at all levels are discussed. They include public awareness and understanding, general approach to toxicology, quality structure-activity relationships, epidemiological studies, quantification of risk, and the types of toxicants studied. (JN)

  3. Toxicology ontology perspectives.

    PubMed

    Hardy, Barry; Apic, Gordana; Carthew, Philip; Clark, Dominic; Cook, David; Dix, Ian; Escher, Sylvia; Hastings, Janna; Heard, David J; Jeliazkova, Nina; Judson, Philip; Matis-Mitchell, Sherri; Mitic, Dragana; Myatt, Glenn; Shah, Imran; Spjuth, Ola; Tcheremenskaia, Olga; Toldo, Luca; Watson, David; White, Andrew; Yang, Chihae

    2012-01-01

    The field of predictive toxicology requires the development of open, public, computable, standardized toxicology vocabularies and ontologies to support the applications required by in silico, in vitro, and in vivo toxicology methods and related analysis and reporting activities. In this article we review ontology developments based on a set of perspectives showing how ontologies are being used in predictive toxicology initiatives and applications. Perspectives on resources and initiatives reviewed include OpenTox, eTOX, Pistoia Alliance, ToxWiz, Virtual Liver, EU-ADR, BEL, ToxML, and Bioclipse. We also review existing ontology developments in neighboring fields that can contribute to establishing an ontological framework for predictive toxicology. A significant set of resources is already available to provide a foundation for an ontological framework for 21st century mechanistic-based toxicology research. Ontologies such as ToxWiz provide a basis for application to toxicology investigations, whereas other ontologies under development in the biological, chemical, and biomedical communities could be incorporated in an extended future framework. OpenTox has provided a semantic web framework for the implementation of such ontologies into software applications and linked data resources. Bioclipse developers have shown the benefit of interoperability obtained through ontology by being able to link their workbench application with remote OpenTox web services. Although these developments are promising, an increased international coordination of efforts is greatly needed to develop a more unified, standardized, and open toxicology ontology framework.

  4. MINING ENVIRONMENTAL TOXICOLOGY INFORMATION WEB RESOURCES

    EPA Science Inventory

    Environmental toxicology is the study of the ecological effects of anthropogenic substances released into the environment. It is a relatively diverse field addressing impacts to aquatic and terrestrial organisms and communities. The determination of potential risk associated with...

  5. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy; Request... Pregnancy Outcomes Associated with Cancer Chemotherapy Use during Pregnancy (available by August 14, 2012... NTP Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy...

  6. A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

    PubMed

    Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A; Perry, Amy; D'Addezio, Alyssa S; Cushing, Bruce S; Patisaul, Heather B

    2014-10-01

    Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.

  7. Toxicological and biochemical responses of the earthworm Eisenia fetida exposed to contaminated soil: Effects of arsenic species.

    PubMed

    Wang, Zhifeng; Cui, Zhaojie; Liu, Lei; Ma, Qianchi; Xu, Xiaoming

    2016-07-01

    Arsenic is a pollutant that can be detected in different chemical forms in soil. However, the toxicological effects of different arsenic species on organisms have received little attention. In this study, we exposed earthworms Eisenia fetida to artificial soils contaminated by arsenite [As(III)], arsenate [As(V)], monomethylarsonate (MMA) and dimethylarsinate (DMA) for 28 and 56 days. Three biomarkers including lipid peroxidation (LPO), metallothioneins (MTs) and lysosomal membrane stability (LMS) were analyzed in the organisms. In addition, the contents of total arsenic and arsenic species in earthworms were also determined to investigate the effects of bioaccumulation and biotransformation of arsenic on biomarkers and to evaluate the dose-response relationships. The results showed that the relationship between the three biomarkers and the two inorganic arsenic species were dose dependent, and the correlation levels between the biomarkers and As(III) were higher than that between the biomarkers and As(V). Trivalent arsenic species shows more toxicity than pentavalent arsenic on the earthworms at molecular and subcellular level, including oxidative damage, MTs induction and lysosomal membrane damage. The toxicity of MMA and DMA was lower than inorganic arsenic species. However, the occurrence of demethylation of organic arsenics could lead to the generation of highly toxic inorganic arsenics and induce adverse effects on organisms. The biotransformation of highly toxic inorganic arsenics to the less toxic organic species in the earthworms was also validated in this study. The biomarker responses of the earthworm to different arsenic species found in this study could be helpful in future environment monitoring programs. PMID:27045633

  8. Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

    PubMed Central

    Inkielewicz-Stepniak, Iwona; Santos-Martinez, Maria Jose; Medina, Carlos; Radomski, Marek W

    2014-01-01

    Background Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells. Methods Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK) was studied using Western blot. Results We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK. Conclusion A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate pharmacological and potentially toxicological effects of AgNPs and F on oral health. PMID:24729703

  9. Metabolic profiling studies on the toxicological effects of realgar in rats by {sup 1}H NMR spectroscopy

    SciTech Connect

    Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing Pei Fengkui Li Weisheng; Wu Yijie

    2009-02-01

    The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of {sup 1}H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. {sup 1}H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine.

  10. Ecological and physiological/toxicological effects of petroleum on aquatic birds

    USGS Publications Warehouse

    Stickel, L.F.; Dieter, M.P.; Tait, H.D.; Hall, C.

    1979-01-01

    The physiological and ecological effects of oil on waterbirds were examined in a series of laboratory and field experiments. Chemical methodology was developed in support of these studies. Research conducted from 1 July 1975 to 30 September 1978 by the US Fish and Wildlife Service about the effects of petroleum on aquatic birds is summarized. The following assessments were made: effects of oiling on hatchability of eggs; effects of oil ingestion on physiological condition and survival of birds; effects of oil ingestion on reproduction in birds; accumulation and loss of oil by birds; and development of analytical methods for identification and quantification of oil breakdown products in tissues and eggs of ducks.

  11. Principles and procedures in forensic toxicology.

    PubMed

    Wyman, John F

    2012-09-01

    The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

  12. The accumulation, distribution, and toxicological effects of dietary arsenic exposure in lake whitefish (Coregonus clupeaformis) and lake trout (Salvelinus namaycush).

    PubMed

    Pedlar, R M; Ptashynski, M D; Wautier, K G; Evans, R E; Baron, C L; Klaverkamp, J F

    2002-01-01

    A 20-day experiment was conducted to compare the accumulation, distribution, and toxicological effects of dietary As, as arsenate, in lake whitefish (LWF, Coregonus clupeaformis) and lake trout (LT, Salvelinus namaycush). Results of this experiment were used to design an experiment of longer duration in which one of the fish species was selected and exposed three times per week to lower dietary As doses. In the present study each treatment group was exposed to a combination of one of three doses of As (0, 100, or 1000 microg As/g) and one of two types of diet, no brine shrimp (NS) or with brine shrimp (WS) for a total of eight dosing events. Brine shrimp were added to determine whether their presence enhanced consumption of As-contaminated food. Modified feeding behavior occurred in both fish species fed As contaminated diets, with the exception of the 100 microg As/g NS food. Brine shrimp addition did not affect feed consumption of the As contaminated diets. Significant As accumulation occurred in stomach, pyloric caeca, intestine, liver, kidney, and gallbladder, but not in bile or muscle. As exposure did not have a significant effect on hepatic and renal metallothionein concentrations. Concentrations of lipid peroxides were only significantly elevated in the plasma of LT fed the 1000 microg As/g WS food. Liver somatic indices decreased significantly in both species, whereas hematological parameters were not affected in either species. Histological lesions occurred in gallbladder, liver, kidney, pyloric caeca and intestine from LWF. These lesions were not observed in LT; however, gallbladders were not examined in this species. Weight gain was lower in both species fed As contaminated diets, however, condition factors were not affected. PMID:11796327

  13. Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium

    SciTech Connect

    Dalton, T.; Kai Fu; Andrews, G.K.; Enders, G.C.; Palmiter, R.D.

    1996-01-01

    Exposure to low levels of cadmium reduces fertility. In male mice spermatogensis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 {mu}mol Cd/Kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 {mu}mol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 {mu}mol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility. 65 refs., 6 figs., 1 tab.

  14. Analysis of the effects of overexpression of metallothionein-I in transgenic mice on the reproductive toxicology of cadmium.

    PubMed

    Dalton, T; Fu, K; Enders, G C; Palmiter, R D; Andrews, G K

    1996-01-01

    Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. Transgenic and control males were injected with cadmium, and the histology of the testes was examined. An injection of 7.5 mumol Cd/kg had no effect on histology of the testes in either transgenic or control mice. In contrast, an injection of 10 mumol Cd/kg caused rapid changes in the histology of the testes and resulted in pronounced testicular necrosis in both control and transgenic mice. Female transgenic and control mice were mated and then injected with cadmium (30-45 mumol Cd/kg) on the day of blastocyst implantation (day 4). In both of these groups, injection of cadmium reduced pregnancy rate, and no dramatic protection was afforded by maternal and/or embryonic overexpression of MT. Thus, overexpression of MT-I does not significantly protect against either of these cadmium-induced effects on fertility. PMID:8834864

  15. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

    The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

  16. Toxicological effects of pet food ingredients on canine bone marrow-derived mesenchymal stem cells and enterocyte-like cells.

    PubMed

    Ortega, M T; Jeffery, B; Riviere, J E; Monteiro-Riviere, N A

    2016-02-01

    We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml(-1) for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml(-1) for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml(-1) for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml(-1) for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml(-1) for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml(-1) for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml(-1) for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml(-1) for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml(-1) for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml(-1) for ginger root extract; > 200 and 116.78 ± 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003-0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells. PMID

  17. Toxicological effects of pet food ingredients on canine bone marrow-derived mesenchymal stem cells and enterocyte-like cells.

    PubMed

    Ortega, M T; Jeffery, B; Riviere, J E; Monteiro-Riviere, N A

    2016-02-01

    We developed an in vitro method to assess pet food ingredients safety. Canine bone marrow-derived mesenchymal stem cells (BMSC) were differentiated into enterocyte-like cells (ELC) to assess toxicity in cells representing similar patterns of exposure in vivo. The toxicological profile of clove leave oil, eugenol, guanosine monophosphate (GMP), GMP + inosine monophosphate, sorbose, ginger root extract, cinnamon bark oil, cinnamaldehyde, thyme oil, thymol and citric acid was assessed in BMSC and ELC. The LC50 for GMP + inosine monophosphate was 59.42 ± 0.90 and 56.7 ± 3.5 mg ml(-1) for BMSC and ELC; 56.84 ± 0.95 and 53.66 ± 1.36 mg ml(-1) for GMP; 0.02 ± 0.001 and 1.25 ± 0.47 mg ml(-1) for citric acid; 0.077 ± 0.002 and 0.037 ± 0.01 mg ml(-1) for cinnamaldehyde; 0.002 ± 0.0001 and 0.002 ± 0.0008 mg ml(-1) for thymol; 0.080 ± 0.003 and 0.059 ± 0.001 mg ml(-1) for thyme oil; 0.111 ± 0.002 and 0.054 ± 0.01 mg ml(-1) for cinnamon bark oil; 0.119 ± 0.0004 and 0.099 ± 0.011 mg ml(-1) for clove leave oil; 0.04 ± 0.001 and 0.028 ± 0.002 mg ml(-1) for eugenol; 2.80 ± 0.11 and 1.75 ± 0.51 mg ml(-1) for ginger root extract; > 200 and 116.78 ± 7.35 mg ml(-1) for sorbose. Lemon grass oil was evaluated at 0.003-0.9 in BMSC and .03-0.9 mg ml(-1) in ELC and its mechanistic effect was investigated. The gene toxicology studies showed regulation of 61% genes in CYP450 pathway, 37% in cholestasis and 33% in immunotoxicity pathways for BMSC. For ELC, 80% for heat shock response, 69% for beta-oxidation and 65% for mitochondrial energy metabolism. In conclusion, these studies provide a baseline against which differential toxicity of dietary feed ingredients can be assessed in vitro for direct effects on canine cells and demonstrate differential toxicity in differentiated cells that represent gastrointestinal epithelial cells.

  18. SOURCES OF VARIATION IN TOXICOLOGICAL STUDIES AND THEIR EFFECTS ON PRECISION OF RESULTS: INDIVIDUAL DIFFERENCES.

    EPA Science Inventory

    The ultimate goal of risk assessment is to estimate the adverse effects of exposures to environmental contaminants in the population. However, populations of humans and other species vary widely in many key factors such as age, genetic makeup, gender, and health status. Any or a...

  19. The toxicological effect of Ruta graveolens extract in Siamese fighting fish: a behavioral and histopathological approach.

    PubMed

    Forsatkar, Mohammad Navid; Nematollahi, Mohammad Ali; Brown, Culum

    2016-05-01

    The effects of pharmacological waste on aquatic ecosystems are increasingly highlighted in ecotoxicology research. Many of these products are designed for human physiology but owing to the conservative nature of vertebrate evolution they also tend to have effects on aquatic organisms and fishes in particular when they find their way into aquatic systems via wastewater effluent. One area of research has focused on reproductive control and the associated hormone treatments. Many of these hormones affect the reproductive physiology of fishes and may cause feminization of male reproductive traits. Alternative medicines have also been widely used particularly in traditional cultures but few of these alternative treatments have been assessed with respect to their potential impact on aquatic ecosystems. Rue (Ruta graveolens) has been used as a male contraceptive in traditional medicines but its effects on fish behavior and reproductive anatomy have yet to be established. Here we show that treating Siamese fighting fish, Betta splendens, with extract of rue has a significant effect on key aggressive/reproductive behaviors and the propensity to explore novel objects (boldness). In all cases the respective behaviors were reduced relative to controls and sham injected fish. Histological analysis of the testes revealed that rue exposure reduced the number of spermatozoa but increased the number of spermatocytes relative to controls.

  20. The effect of silver nanoparticles on zebrafish embryonic development and toxicology.

    PubMed

    Xia, Guangqing; Liu, Tiantian; Wang, Zhenwei; Hou, Yi; Dong, Lihong; Zhu, Junyi; Qi, Jie

    2016-06-01

    The unique physical and chemical characteristics of nanomaterials, such as the effects of their small size, surface effects, very high rates of reaction, and quantum tunnel effect, have aroused great interest among scholars. However, improper usage has led to an increasing number of nanomaterials entering the environment through various channels, greatly threatening the security of the ecological environment and human health. The urgent need for a scientific assessment of their biosafety can enable nanomaterials to truly benefit humanity. However, the current research in this field is extremely limited with regard to safety standards and waste disposal. In this study, we used silver nanoparticles (nano-Ag) and zebrafish embryos as experimental subjects, and we have reported the deleterious effect on zebrafish embryos treated with different concentrations of nano-Ag, with respect to morphological features (mortality, deformity rate, and heartbeat) and the analysis of expression of relevant genes (sox17, gsc, ntl, otx2); we found a dose-dependent increase in mortality and hatching delay. The results of in situ hybridization indicated that nano-Ag causes a dose-dependent toxicity in embryonic development, and would affect their development and lead to deformity, delayed development, and even death. The safety limit for the concentration of nano-Ag was found to be less than 5 mg/L. PMID:25749278

  1. The toxicological effect of Ruta graveolens extract in Siamese fighting fish: a behavioral and histopathological approach.

    PubMed

    Forsatkar, Mohammad Navid; Nematollahi, Mohammad Ali; Brown, Culum

    2016-05-01

    The effects of pharmacological waste on aquatic ecosystems are increasingly highlighted in ecotoxicology research. Many of these products are designed for human physiology but owing to the conservative nature of vertebrate evolution they also tend to have effects on aquatic organisms and fishes in particular when they find their way into aquatic systems via wastewater effluent. One area of research has focused on reproductive control and the associated hormone treatments. Many of these hormones affect the reproductive physiology of fishes and may cause feminization of male reproductive traits. Alternative medicines have also been widely used particularly in traditional cultures but few of these alternative treatments have been assessed with respect to their potential impact on aquatic ecosystems. Rue (Ruta graveolens) has been used as a male contraceptive in traditional medicines but its effects on fish behavior and reproductive anatomy have yet to be established. Here we show that treating Siamese fighting fish, Betta splendens, with extract of rue has a significant effect on key aggressive/reproductive behaviors and the propensity to explore novel objects (boldness). In all cases the respective behaviors were reduced relative to controls and sham injected fish. Histological analysis of the testes revealed that rue exposure reduced the number of spermatozoa but increased the number of spermatocytes relative to controls. PMID:26924199

  2. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    SciTech Connect

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K. )

    1989-10-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance.

  3. Effects of four rice herbicides on some metabolic and toxicology parameters of teleost fish (Leporinus obtusidens).

    PubMed

    Moraes, Bibiana Silveira; Loro, Vania Lúcia; Glusczak, Lissandra; Pretto, Alexandra; Menezes, Charlene; Marchezan, Enio; de Oliveira Machado, Sérgio

    2007-07-01

    Effects of different herbicides on acetylcholinesterase (AChE), catalase and TBARS formation in teleost fish (Leporinus obtusidens) were studied. Fish were exposed during 30 days at concentrations of herbicides used in rice field. AChE activity in the brain decreased significantly after exposure to the herbicides clomazone and quinclorac. However, AChE activity increased significantly in muscle tissue after exposure to clomazone, propanil and metsulfuron methyl. Fish exposed to quinclorac, propanil and metsulfuron methyl showed TBARS decreased levels in brain and muscle tissues. However, TBARS and catalase activity increased in liver tissue after clomazone and propanil exposure. This study pointed out long-term effects on AChE activity, oxidative stress and antioxidant enzyme catalase in tissues of L. obtusidens after exposure to environmentally relevant concentrations of rice field herbicides. These parameters have been used to monitor fish toxicity in rice field system.

  4. Toxicological impact of cadmium-based quantum dots towards aquatic biota: Effect of natural sunlight exposure.

    PubMed

    Silva, B F; Andreani, T; Gavina, A; Vieira, M N; Pereira, C M; Rocha-Santos, T; Pereira, R

    2016-07-01

    Cadmium-based quantum dots (QDs) are increasingly applied in existent and emerging technologies, especially in biological applications due to their exceptional photophysical and functionalization properties. However, they are very toxic compounds due to the high reactive and toxic cadmium core. The present study aimed to determine the toxicity of three different QDs (CdS 380, CdS 480 and CdSeS/ZnS) before and after the exposure of suspensions to sunlight, in order to assess the effect of environmentally relevant irradiation levels in their toxicity, which will act after their release to the environment. Therefore, a battery of ecotoxicological tests was performed with organisms that cover different functional and trophic levels, such as Vibrio fischeri, Raphidocelis subcapitata, Chlorella vulgaris and Daphnia magna. The results showed that core-shell type QDs showed lower toxic effects to V. fischeri in comparison to core type QDs before sunlight exposure. However, after sunlight exposure, there was a decrease of CdS 380 and CdS 480 QD toxicity to bacterium. Also, after sunlight exposure, an effective decrease of CdSeS/ZnS and CdS 480 toxicity for D. magna and R. subcapitata, and an evident increase in CdS 380 QD toxicity, at least for D. magna, were observed. The results of this study suggest that sunlight exposure has an effect in the aggregation and precipitation reactions of larger QDs, causing the degradation of functional groups and formation of larger bulks which may be less prone to photo-oxidation due to their diminished surface area. The same aggregation behaviour after sunlight exposure was observed for bare QDs. These results further emphasize that the shell of QDs seems to make them less harmful to aquatic biota, both under standard environmental conditions and after the exposure to a relevant abiotic factor like sunlight. PMID:27162069

  5. Toxicological impact of cadmium-based quantum dots towards aquatic biota: Effect of natural sunlight exposure.

    PubMed

    Silva, B F; Andreani, T; Gavina, A; Vieira, M N; Pereira, C M; Rocha-Santos, T; Pereira, R

    2016-07-01

    Cadmium-based quantum dots (QDs) are increasingly applied in existent and emerging technologies, especially in biological applications due to their exceptional photophysical and functionalization properties. However, they are very toxic compounds due to the high reactive and toxic cadmium core. The present study aimed to determine the toxicity of three different QDs (CdS 380, CdS 480 and CdSeS/ZnS) before and after the exposure of suspensions to sunlight, in order to assess the effect of environmentally relevant irradiation levels in their toxicity, which will act after their release to the environment. Therefore, a battery of ecotoxicological tests was performed with organisms that cover different functional and trophic levels, such as Vibrio fischeri, Raphidocelis subcapitata, Chlorella vulgaris and Daphnia magna. The results showed that core-shell type QDs showed lower toxic effects to V. fischeri in comparison to core type QDs before sunlight exposure. However, after sunlight exposure, there was a decrease of CdS 380 and CdS 480 QD toxicity to bacterium. Also, after sunlight exposure, an effective decrease of CdSeS/ZnS and CdS 480 toxicity for D. magna and R. subcapitata, and an evident increase in CdS 380 QD toxicity, at least for D. magna, were observed. The results of this study suggest that sunlight exposure has an effect in the aggregation and precipitation reactions of larger QDs, causing the degradation of functional groups and formation of larger bulks which may be less prone to photo-oxidation due to their diminished surface area. The same aggregation behaviour after sunlight exposure was observed for bare QDs. These results further emphasize that the shell of QDs seems to make them less harmful to aquatic biota, both under standard environmental conditions and after the exposure to a relevant abiotic factor like sunlight.

  6. Toxicological effect of single contaminants and contaminant mixtures associated with plant ingredients in novel salmon feeds.

    PubMed

    Søfteland, Liv; Kirwan, Jennifer A; Hori, Tiago S F; Størseth, Trond R; Sommer, Ulf; Berntssen, Marc H G; Viant, Mark R; Rise, Matthew L; Waagbø, Rune; Torstensen, Bente E; Booman, Marije; Olsvik, Pål A

    2014-11-01

    Increasing use of plant feed ingredients may introduce contaminants not previously associated with farming of salmonids, such as pesticides and PAHs from environmental sources or from thermal processing of oil seeds. To screen for interaction effects of contaminants newly introduced in salmon feeds, Atlantic salmon primary hepatocytes were used. The xCELLigence cytotoxicity system was used to select optimal dosages of the PAHs benzo(a)pyrene and phenanthrene, the pesticides chlorpyrifos and endosulfan, and combinations of these. NMR and MS metabolic profiling and microarray transcriptomic profiling was used to identify novel biomarkers. Lipidomic and transcriptomic profiling suggested perturbation of lipid metabolism, as well as endocrine disruption. The pesticides gave the strongest responses, despite having less effect on cell viability than the PAHs. Only weak molecular responses were detected in PAH-exposed hepatocytes. Chlorpyrifos suppressed the synthesis of unsaturated fatty acids. Endosulfan affected steroid hormone synthesis, while benzo(a)pyrene disturbed vitamin D3 metabolism. The primary mixture effect was additive, although at high concentrations the pesticides acted in a synergistic fashion to decrease cell viability and down-regulate CYP3A and FABP4 transcription. This work highlights the usefulness of 'omics techniques and multivariate data analysis to investigate interactions within mixtures of contaminants with different modes of action. PMID:25193261

  7. Toxicological effect of single contaminants and contaminant mixtures associated with plant ingredients in novel salmon feeds.

    PubMed

    Søfteland, Liv; Kirwan, Jennifer A; Hori, Tiago S F; Størseth, Trond R; Sommer, Ulf; Berntssen, Marc H G; Viant, Mark R; Rise, Matthew L; Waagbø, Rune; Torstensen, Bente E; Booman, Marije; Olsvik, Pål A

    2014-11-01

    Increasing use of plant feed ingredients may introduce contaminants not previously associated with farming of salmonids, such as pesticides and PAHs from environmental sources or from thermal processing of oil seeds. To screen for interaction effects of contaminants newly introduced in salmon feeds, Atlantic salmon primary hepatocytes were used. The xCELLigence cytotoxicity system was used to select optimal dosages of the PAHs benzo(a)pyrene and phenanthrene, the pesticides chlorpyrifos and endosulfan, and combinations of these. NMR and MS metabolic profiling and microarray transcriptomic profiling was used to identify novel biomarkers. Lipidomic and transcriptomic profiling suggested perturbation of lipid metabolism, as well as endocrine disruption. The pesticides gave the strongest responses, despite having less effect on cell viability than the PAHs. Only weak molecular responses were detected in PAH-exposed hepatocytes. Chlorpyrifos suppressed the synthesis of unsaturated fatty acids. Endosulfan affected steroid hormone synthesis, while benzo(a)pyrene disturbed vitamin D3 metabolism. The primary mixture effect was additive, although at high concentrations the pesticides acted in a synergistic fashion to decrease cell viability and down-regulate CYP3A and FABP4 transcription. This work highlights the usefulness of 'omics techniques and multivariate data analysis to investigate interactions within mixtures of contaminants with different modes of action.

  8. Pharmacology, toxicology, clinical efficacy, and adverse effects of calcium polycarbophil, an enteral hydrosorptive agent.

    PubMed

    Danhof, I E

    1982-01-01

    Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non-toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double-blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk-forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.

  9. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    SciTech Connect

    Tassinari, Roberta; La Rocca, Cinzia; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca; Stecca, Laura

    2015-06-23

    In European Union, titanium dioxide (TiO{sub 2}) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO{sub 2} NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO{sub 2} NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO{sub 2} NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm{sup 2} levels of TiO{sub 2} NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO{sub 2} NP toxicity by direct exposure both in vivo and in vitro models.

  10. In vivo and in vitro toxicological effects of titanium dioxide nanoparticles on small intestine

    NASA Astrophysics Data System (ADS)

    Tassinari, Roberta; La Rocca, Cinzia; Stecca, Laura; Tait, Sabrina; De Berardis, Barbara; Ammendolia, Maria Grazia; Iosi, Francesca; Di Virgilio, Antonio; Martinelli, Andrea; Maranghi, Francesca

    2015-06-01

    In European Union, titanium dioxide (TiO2) as bulk material is a food additive (E171) and - as nanoparticle (NP) - is used as a white pigment in several products (e.g. food, cosmetics, drugs). E171 contains approximately 36% of particles less than 100 nm in at least one dimension and TiO2 NP exposure is estimated fairly below 2.5 mg/person/day. The gastrointestinal tract is a route of entry for NPs, thus representing a potential target of effects. In in vivo study, the effects of TiO2 NP in adult rat small intestine have been evaluated by oral administration of 0 (CTRL), 1 and 2 mg/kg body weight per day - relevant to human dietary intake. Detailed quali/quantitative histopathological analyses were performed on CTRL and treated rat samples. Scanning electron microscopy (SEM) analysis was performed on small intestine. An in vitro study on Caco-2 cells was also used in order to evaluate the potential cytotoxic effects directly on enterocytes through the lactate dehydrogenase (LDH) assay. Suspensions of TiO2 NPs for in vitro and in vivo study were characterized by EM. Histomorphometrical data showed treatment-related changes of villus height and widths in male rats. Significantly different from CTRL decreased LDH levels in the medium were detected in vitro at 24h with 2.5, 5, 10 and 20 µg/cm2 levels of TiO2 NPs. SEM analysis showed no damaged areas. Overall the results showed that enterocytes may represent a target of TiO2 NP toxicity by direct exposure both in vivo and in vitro models.

  11. Toxicological investigations of pollutant-related effects in Great Lakes gulls.

    PubMed Central

    Peakall, D B; Fox, G A

    1987-01-01

    Reproductive failure of a number of fish-eating birds was observed on the Great Lakes in the mid-1960s to mid-1970s. The herring gull (Larus argentatus) has been used as the primary monitoring species. The low hatching success observed in this species on Lake Ontario in the mid-1970s was due to loss of eggs and failure of eggs to hatch. Egg exchange experiments demonstrated that this was due both to the incubation behavior of adults and to direct embryotoxic effects. Decrease of nest attentiveness was demonstrated using telemetered eggs, but attempts to reproduce the embryonic effects by injection of pollutant mixtures into eggs were not successful. Reproductive success improved rapidly during the late 1970s and was normal by the end of the decade. Recent studies have focused on cytogenetic and biochemical changes and detailed analytical chemistry of residues. No changes in the rate of sister chromatid exchange over values determined in coastal colonies were observed. Elevation of hepatic aryl hydrocarbon hydroxylase activity, levels of highly carboxylated porphyrins, and changes of thyroid function have been found. The geographic pattern of these changes indicates that they are caused by xenobiotics, but it has not been possible to relate the changes to a specific chemical. PMID:3297661

  12. Magnetite nanoparticle (NP) uptake by wheat plants and its effect on cadmium and chromium toxicological behavior.

    PubMed

    López-Luna, J; Silva-Silva, M J; Martinez-Vargas, S; Mijangos-Ricardez, O F; González-Chávez, M C; Solís-Domínguez, F A; Cuevas-Díaz, M C

    2016-09-15

    The aim of this work was to assess the uptake of citrate-coated magnetite nanoparticles (NPs) by wheat plants and its effect on the bioaccumulation and toxicity of individual and joint Cd(2+) and Cr(6+) levels. Seven-day assays were conducted using quartz sand as the plant growth substrate. The endpoints measured were seed germination, root and shoot lengths, and heavy metal accumulation. Magnetite exhibited very low toxicity, regardless of the wheat seedling NP uptake and distribution into roots and shoots. The seed germination and shoot length were not sensitive enough, while the root length was a more sensitive toxicity endpoint. The root length of wheat seedlings exposed to individual metals decreased by 50% at 2.67mgCd(2)(+)kg(-1) and 5.53mgCr(6+)kg(-1). However, when magnetite NPs (1000mgkg(-1)) were added, the root length of the plants increased by 25 and 50%. Cd(2+) and Cr(6+) showed similar and noninteractive joint action, but strongly impaired the wheat seedlings. In contrast, an interactive infra-additive or antagonistic effect was observed upon adding magnetite NPs. Thus, cadmium and chromium accumulation in vegetable tissues was considerately diminished and the toxicity alleviated. PMID:26806072

  13. Magnetite nanoparticle (NP) uptake by wheat plants and its effect on cadmium and chromium toxicological behavior.

    PubMed

    López-Luna, J; Silva-Silva, M J; Martinez-Vargas, S; Mijangos-Ricardez, O F; González-Chávez, M C; Solís-Domínguez, F A; Cuevas-Díaz, M C

    2016-09-15

    The aim of this work was to assess the uptake of citrate-coated magnetite nanoparticles (NPs) by wheat plants and its effect on the bioaccumulation and toxicity of individual and joint Cd(2+) and Cr(6+) levels. Seven-day assays were conducted using quartz sand as the plant growth substrate. The endpoints measured were seed germination, root and shoot lengths, and heavy metal accumulation. Magnetite exhibited very low toxicity, regardless of the wheat seedling NP uptake and distribution into roots and shoots. The seed germination and shoot length were not sensitive enough, while the root length was a more sensitive toxicity endpoint. The root length of wheat seedlings exposed to individual metals decreased by 50% at 2.67mgCd(2)(+)kg(-1) and 5.53mgCr(6+)kg(-1). However, when magnetite NPs (1000mgkg(-1)) were added, the root length of the plants increased by 25 and 50%. Cd(2+) and Cr(6+) showed similar and noninteractive joint action, but strongly impaired the wheat seedlings. In contrast, an interactive infra-additive or antagonistic effect was observed upon adding magnetite NPs. Thus, cadmium and chromium accumulation in vegetable tissues was considerately diminished and the toxicity alleviated.

  14. Toxicological evaluation of polyphenol extract from Acerola (Malpighia emarginata DC.) fruit.

    PubMed

    Hanamura, T; Aoki, H

    2008-05-01

    Acerola (Malpighia emarginata DC.) is known to be one of the best fruits rich in ascorbic acid and polyphenols. Acerola polyphenols (APs) were found to have radical scavenging activities and inhibitory effects on both alpha-glucosidase and advanced glycation endproducts (AGEs) production. While polyphenols from several foodstuffs have been shown to be safe, APs, which differ from those of other foodstuffs, have not been evaluated for their toxicological properties. Here, we report preliminary toxicological and safety evaluations of crude APs (C-AP), which were obtained by eluting an XAD7HP column-adsorbed fraction of APs with 70% ethanol containing malic acid. The total polyphenol content of C-AP was 57.7% with the main polyphenols being proanthocyanidin and cyanidin-3-alpha-O-rhamnoside. For toxicological evaluations, C-AP was administered orally to rats at doses of 2000 mg/kg body weight (acute) or 100, 300, and 1000 mg/kg body weight/d for 28 (subacute) and 90 (subchronic) d. In the acute oral toxicological test, no deaths or abnormalities at necropsy on day 14 were observed, confirming that the minimum fatal dose of C-AP is greater than 2000 mg/kg body weight. In both subacute and subchronic toxicological tests, no death was recorded and the body weights and food intakes of the rats did not differ significantly from the control groups. Besides, there were no abnormal clinical signs related to administration of C-AP in any of the experimental animals. These results provide an important reference for the safety of APs as a food supplement for human consumption.

  15. Preliminary Toxicological Analysis of the Effect of Coal Slurry Impoundment Water on Human Liver Cells

    USGS Publications Warehouse

    Bunnell, Joseph E.

    2008-01-01

    Coal is usually 'washed' with water and a variety of chemicals to reduce its content of sulfur and mineral matter. The 'washings' or 'coal slurry' derived from this process is a viscous black liquid containing fine particles of coal, mineral matter, and other dissolved and particulate substances. Coal slurry may be stored in impoundments or in abandoned underground mines. Human health and environmental effects potentially resulting from leakage of chemical substances from coal slurry into drinking water supplies or aquatic ecosystems have not been systematically examined. Impoundments are semipermeable, presenting the possibility that inorganic and organic substances, some of which may be toxic, may contaminate ground or surface water. The Agency for Toxic Substances and Disease Registry, part of the Centers for Disease Control and Prevention, has concluded that well water in Mingo County, West Virginia, constitutes a public health hazard.

  16. Toxicology: Mechanisms of deuterium oxide action, part 2. [deuterium oxide effect on growth of winter rye

    NASA Technical Reports Server (NTRS)

    Siegel, S. M.

    1973-01-01

    The metabolism of winter rye seedlings (Secale cereale, L. cv. Winter) cultured in 99.6% D2O was investigated. Compared with water grown seedlings, the protein content was much lower in the D2O cultured seedlings and the incorporation of H(3)-leucine and H(3)-phenylalanine into medium to high molecular weight proteins was partially blocked. The synthesis of the enzyme peroxidase was also reduced in the D2O plants. Seedlings cultured in D2O incorporate H(3)-thymidine into DNA, but do not take up H(3)-uridine. These results suggest that some of the toxic effects of D2O culture on higher plants can be attributed to a partial block of protein synthesis.

  17. [Toxicological effects of weapons of mass destruction and noxious agents in modern warfare and terrorism].

    PubMed

    Vucemilović, Ante

    2010-06-01

    Weapons of mass destruction (WMD) best portray the twisted use of technological achievements against the human species. Despite arm control efforts, WMD threat continues to exist and even proliferate. This in turn calls for improvement in defensive measures against this threat. The modern soldier is exposed to a number of chemical, biological, and radiological agents in military and peace operations, while civilians are mainly exposed to terrorist attacks. Regardless of origin or mode of action, WMDs and other noxious agents aim for the same - to make an organism dysfunctional. Because their effects are often delayed, these agents are hard to spot on time and treat. This review presents a biomedical aspect of agents used in warfare and terrorism, including polonium-210, depleted uranium, salmonella, anthrax, genetically modified bacteria, cobweb-like polymer fibre, sarin, and mustard gas.

  18. National Toxicology Program

    MedlinePlus

    ... improved search is live. Try it now! NTP Cell Phone Radiofrequency Radiation Studies The National Toxicology Program (NTP) ... rats and mice on potential health hazards from cell phone radiofrequency radiation. The NTP released a report on ...

  19. Computational Toxicology (S)

    EPA Science Inventory

    The emerging field of computational toxicology applies mathematical and computer models and molecular biological and chemical approaches to explore both qualitative and quantitative relationships between sources of environmental pollutant exposure and adverse health outcomes. Th...

  20. Chemical constituents and toxicological studies of leaves from Mimosa caesalpiniifolia Benth., a Brazilian honey plant

    PubMed Central

    Monção, Nayana Bruna Nery; Costa, Luciana Muratori; Arcanjo, Daniel Dias Rufino; Araújo, Bruno Quirino; Lustosa, Maria do Carmo Gomes; Rodrigues, Klinger Antônio da França; Carvalho, Fernando Aécio de Amorim; Costa, Amilton Paulo Raposo; Lopes Citó, Antônia Maria das Graças

    2014-01-01

    Background: Mimosa caesalpiniifolia Benth. (Leguminosae) is widely found in the Brazilian Northeast region and markedly contributes to production of pollen and honey, being considered an important honey plant in this region. Objective: To investigate the chemical composition of the ethanol extract of leaves from M. caesalpiniifolia by GC-MS after derivatization (silylation), as well as to evaluate the in vitro and in vivo toxicological effects and androgenic activity in rats. Materials and Methods: The ethanol extract of leaves from Mimosa caesalpiniifolia was submitted to derivatization by silylation and analyzed by gas chromatography-mass spectrometry (GC-MS) to identification of chemical constituents. In vitro toxicological evaluation was performed by MTT assay in murine macrophages and by Artemia salina lethality assay, and the in vivo acute oral toxicity and androgenic evaluation in rats. Results: Totally, 32 components were detected: Phytol-TMS (11.66%), lactic acid-2TMS (9.16%), α-tocopherol-TMS (7.34%) and β-sitosterol-TMS (6.80%) were the major constituents. At the concentrations analyzed, the ethanol extract showed low cytotoxicity against brine shrimp (Artemia salina) and murine macrophages. In addition, the extract did not exhibit any toxicological effect or androgenic activity in rats. Conclusions: The derivatization by silylation allowed a rapid identification of chemical compounds from the M. caesalpiniifolia leaves extract. Besides, this species presents a good safety profile as observed in toxicological studies, and possess a great potential in the production of herbal medicines or as for food consumption. PMID:25298660

  1. Effects of developmental stage, salts, and food presence on aquatic toxicological endpoints using Caenorhabditis elegans

    SciTech Connect

    Donkin, S.G.; Williams, P.L.

    1995-12-31

    The objective of this study was to standardize the testing protocol for aquatic toxicity tests with the nematode Caenorhabditis elegans. Several variables which may be important in determining the test outcome were investigated in a randomized block design. Concentration-response data were obtained on nematodes of various developmental stages exposed to four metals (Cd, Pb, Cu, and Hg) and a water-soluble organic toxicant, sodium Pentachlorophenate (PCP), under conditions of varied solvent medium (with or without salts and with or without a bacterial food source). The endpoints measured were 24 and 96-h mortality, as well as development of larval stages to adulthood and evidence of reproduction. The results suggest that nematodes of various ages respond similarly to a given toxicant for all endpoints measured, although adults cultured from eggs appeared more sensitive than adults cultured from dauer larvae. The most important environmental variable in determining toxicity was the medium in which the tests were conducted. The presence of potassium and sodium salts in the medium significantly (p<0.05) reduced the toxicity of many test samples. The presence of bacteria had little effect on 24-h tests with salts, but was important in 96-h survival and development. Based on sensitivity and ease of handling, adults cultured from eggs are recommended in both 24-h and 96-h mortality (LC50 value) tests, as well as 96-h reproduction tests.

  2. Toxicological benchmarks for screening potential contaminants of concern for effects on terrestrial plants: 1994 revision

    SciTech Connect

    Will, M.E.; Suter, G.W. II

    1994-09-01

    One of the initial stages in ecological risk assessment for hazardous waste sites is screening contaminants to determine which of them are worthy of further consideration as contaminants of potential concern. This process is termed contaminant screening. It is performed by comparing measured ambient concentrations of chemicals to benchmark concentrations. Currently, no standard benchmark concentrations exist for assessing contaminants in soil with respect to their toxicity to plants. This report presents a standard method for deriving benchmarks for this purpose (phytotoxicity benchmarks), a set of data concerning effects of chemicals in soil or soil solution on plants, and a set of phytotoxicity benchmarks for 38 chemicals potentially associated with United States Department of Energy (DOE) sites. In addition, background information on the phytotoxicity and occurrence of the chemicals in soils is presented, and literature describing the experiments from which data were drawn for benchmark derivation is reviewed. Chemicals that are found in soil at concentrations exceeding both the phytotoxicity benchmark and the background concentration for the soil type should be considered contaminants of potential concern.

  3. Toxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Terrestrial Plants

    SciTech Connect

    Suter, G.W. II

    1993-01-01

    One of the initial stages in ecological risk assessment for hazardous waste sites is screening contaminants to determine which of them are worthy of further consideration as contaminants of potential concern. This process is termed contaminant screening. It is performed by comparing measured ambient concentrations of chemicals to benchmark concentrations. Currently, no standard benchmark concentrations exist for assessing contaminants in soil with respect to their toxicity to plants. This report presents a standard method for deriving benchmarks for this purpose (phytotoxicity benchmarks), a set of data concerning effects of chemicals in soil or soil solution on plants, and a set of phytotoxicity benchmarks for 38 chemicals potentially associated with United States Department of Energy (DOE) sites. In addition, background information on the phytotoxicity and occurrence of the chemicals in soils is presented, and literature describing the experiments from which data were drawn for benchmark derivation is reviewed. Chemicals that are found in soil at concentrations exceeding both the phytotoxicity benchmark and the background concentration for the soil type should be considered contaminants of potential concern.

  4. Toxicological benchmarks for screening potential contaminants of concern for effects on terrestrial plants. Environmental Restoration Program

    SciTech Connect

    Suter, G.W. II; Will, M.E.; Evans, C.

    1993-09-01

    One of the initial stages in ecological risk assessment for hazardous waste sites is the screening of contaminants to determine which of them are worthy of further consideration as ``contaminants of potential concern.`` This process is termed ``contaminant screening.`` It is performed by comparing measured ambient concentrations of chemicals to benchmark concentrations. Currently, no standard benchmark concentrations exist for assessing contaminants in soil with respect to their toxicity to plants. This report presents a standard method for deriving benchmarks for this purpose (phytotoxicity benchmarks), a set of data concerning effects of chemicals in soil or soil solution on plants, and a set of phytotoxicity benchmarks for 34 chemicals potentially associated with US Department of Energy (DOE) sites. Chemicals that are found in soil at concentrations exceeding both the phytotoxicity benchmark and the background concentration for the soil type should be considered contaminants of potential concern. The purpose of this report is to present plant toxicity data and discuss their utility as benchmarks for determining the hazard to terrestrial plants caused by contaminants in soil. Benchmarks are provided for soils and solutions.

  5. Toxicological and phytoprotective effect of Keayodendron bridelioides and Monodora myristica extracts in Wister rats

    PubMed Central

    Owumi, Solomon E.; Oloidi, Abiodun C.; Oloye, Cinzia O.; Oladeji, Oludare O.; Obadare, Moses O.; Odunola, Oyeronke A.

    2015-01-01

    Objectives: The potential toxicity of Keayodendron bridelioides (KB), Monodora myristica (MM) were examined, and phytoprotection of MM and KB stemming from their phytochemical contents against sodium arsenite (SA) induced clastogenicity in Wister's rat. Materials and Methods: Dose range studies of KB in rats, genotoxicity of MM and KB by SOS-inductive respomse were investigated using E. coli PQ37. Male rats were exposed to varying concentrations of MM, KB over a five week period to evaluate MM and KB phytoprotectives properties were also evaluated against sodium arsenite induced micronucleated erythrocytes, hepatotoxicity and sperm quality and morphology. Results: In contrast to KB, MM induced micronuclei formation in rat erythrocytes, MM and KB were however not genotoxic. MM, SA alone and in combination were hepatotoxic, characterized by elevated hepatic transaminases. Hepatoxicity were ameliorated by co-administration of KB (P < 0.05). MM and KB did not induce changes in semen morphology (P > 0.05); but decreased sperm count and motility (P < 0.05). Extracts exhibited anti-clastogenic (KB > MM), hepatoprotective (KB > MM) activities and maintained semen viability against SA treatment. Conclusion: Finding applications as herbal medicinal and food components KB and MM may be useful in mitigating the effect of toxicants in biological systems susceptible to oxidative damage. PMID:26109784

  6. Tissue Distribution and Associated Toxicological Effects of Decabrominated Diphenyl Ether in Subchronically Exposed Male Rats

    PubMed Central

    Wang, Fuxin; Wang, Jianshe; Hu, Guocheng; Luo, Xiaojun; Mai, Bixian; Dai, Jiayin

    2011-01-01

    Concerns about decabrominated diphenyl ether (BDE-209) have arisen recently due to its increasing concentrations in the environment. We investigated the tissue concentration, distribution, and the debromination of BDE-209 after oral exposure, using rats as a model. Three groups of male rats were administrated by oral gavage with corn oil containing 0, 10, or 50 mg/kg bw/day of BDE-209 over 90 days. After exposure, BDE-209 and its metabolites levels in the liver, kidney, and adipose of the rats were measured. The mRNA expression levels of cytochrome P450 (CYP) enzymes in liver, serum thyroid hormone levels, and open-field tests were also measured. BDE-209 and several octa- and nona-BDE congeners were detected in the tissues of the dosed rats, indicating that BDE-209 was bioavailable and biotransformative in male rats. BDE-209 and its debrominated congeners had no mRNA level effect on selective genes from the CYP family in the liver or on the spontaneous behavior of adult male rats. Conversely, the level of thyroid hormone, total triiodothyronine (T3) in rats from the dosed treatments increased significantly compared to the control group. PMID:23724291

  7. The effects of orchidectomy on toxicological responses to dietary ochratoxin A in Wistar rats.

    PubMed

    Mor, Firdevs; Kilic, Mehmet A; Ozmen, Ozlem; Yilmaz, Mesut; Eker, Ilknur; Uran, Kemal

    2014-08-01

    Ochratoxin A (OTA) causes pathological lesions in the organs of animals. Males are more sensitive to OTA exposure than females but the reasons for this are unknown. The objective of this study was to explore the role of testosterone in male rats with OTA-related pathogenesis. To test the effect of testosterone on OTA toxicity, the testes of a group of rats were surgically removed. Male and female rats (approximately 300 and 200 g) were fed with OTA-contaminated feed (initially approximately 300 μg kg(-1) b.w. per day) for 24 weeks. The organs of all the animals were collected and their organ lesion pathology, caspase-3 expression, OTA plasma and organ concentrations and total plasma testosterone concentrations were evaluated. OTA treatment created serious lesions in the kidney, liver and testes of rats. The major histopathological changes in the kidney and liver were karyomegaly, hemorrhages and vacuolization. In the testes, there was a marked decrease in the amount of spermatozoon. The degrees of organ lesion were evaluated and the castrated males had the lowest kidney and liver lesion scores, indicating that testosterone reduction in males dramatically reduces OTA-related organ damage. The plasma OTA levels for the intact males, the castrated and the females were 6.34, 8.42 and 12.5 μg ml(-1), respectively. In conclusion, despite the similar plasma OTA levels of the intact and castrated males, OTA is less toxic in the castrated males. Therefore, the well-known gender specific toxicity of OTA seems to be related to the testosterone levels of rats.

  8. Toxicological effects of short-term resuspension of metal-contaminated freshwater and marine sediments.

    PubMed

    Fetters, Kyle J; Costello, David M; Hammerschmidt, Chad R; Burton, G Allen

    2016-03-01

    Sediments in navigation-dominated waterways frequently are contaminated with a variety of particle-associated pollutants and are subject to frequent short-term resuspension events. There is little information documenting whether resuspension of metal-contaminated sediments has adverse ecological effects on resident aquatic organisms. Using a novel laboratory approach, the authors examined the mobilization of Zn, Cu, Cd, Pb, Ni, and Cr during resuspension of 1 freshwater and 2 coastal marine sediments and whether resuspension and redeposition resulted in toxicity to model organisms. Sediment flux exposure chambers were used to resuspend metal-contaminated sediments from 1 site in Lake DePue, Illinois (USA), and 2 sites in Portsmouth Naval Shipyard, Maine (USA). Short-term (4-h) resuspension of sediment at environmentally relevant suspended particulate matter concentrations (<1 g/L) resulted in metal mobilization to water that was sediment and metal specific. Overall, the net release of metals from suspended particles was limited, likely because of scavenging by organic matter and Fe oxides that formed during sediment interaction with oxic water. Minimal toxicity to organisms (survival of Hyalella azteca and Daphnia magna; survival, growth, and tissue metal concentration of Neanthes arenaceodentata; bioluminescence of Pyrocystis lunula) was observed during 4-h exposure to resuspended sediments and during 4-d to 10-d post-exposure recovery periods in uncontaminated water. Redeposited suspended particles exhibited increased metal bioavailability and toxicity to H. azteca, highlighting the potential for adverse ecological impacts because of changes in metal speciation. It is important to consider interactions between organisms' life histories and sediment disturbance regimes when assessing risks to ecosystems.

  9. Chemical and toxicological evaluation of underground coal gasification (UCG) effluents. The coal rank effect.

    PubMed

    Kapusta, Krzysztof; Stańczyk, Krzysztof

    2015-02-01

    The effect of coal rank on the composition and toxicity of water effluents resulting from two underground coal gasification experiments with distinct coal samples (lignite and hard coal) was investigated. A broad range of organic and inorganic parameters was determined in the sampled condensates. The physicochemical tests were supplemented by toxicity bioassays based on the luminescent bacteria Vibrio fischeri as the test organism. The principal component analysis and Pearson correlation analysis were adopted to assist in the interpretation of the raw experimental data, and the multiple regression statistical method was subsequently employed to enable predictions of the toxicity based on the values of the selected parameters. Significant differences in the qualitative and quantitative description of the contamination profiles were identified for both types of coal under study. Independent of the coal rank, the most characteristic organic components of the studied condensates were phenols, naphthalene and benzene. In the inorganic array, ammonia, sulphates and selected heavy metals and metalloids were identified as the dominant constituents. Except for benzene with its alkyl homologues (BTEX), selected polycyclic aromatic hydrocarbons (PAHs), zinc and selenium, the values of the remaining parameters were considerably greater for the hard coal condensates. The studies revealed that all of the tested UCG condensates were extremely toxic to V. fischeri; however, the average toxicity level for the hard coal condensates was approximately 56% higher than that obtained for the lignite. The statistical analysis provided results supporting that the toxicity of the condensates was most positively correlated with the concentrations of free ammonia, phenols and certain heavy metals.

  10. Chemical and toxicological effects of medicinal Baccharis trimera extract from coal burning area.

    PubMed

    Menezes, Ana Paula S; da Silva, Juliana; Fisher, Camila; da Silva, Fernanda R; Reyes, Juliana M; Picada, Jaqueline N; Ferraz, Alice G; Corrêa, Dione S; Premoli, Suziane M; Dias, Johnny F; de Souza, Claudia T; Ferraz, Alexandre de B F

    2016-03-01

    The entire process of power generation, extraction, processing and use of coal strongly impact water resources, soil, air quality and biota leads to changes in the fauna and flora. Pollutants generated by coal burning have been contaminating plants that grow in area impacted by airborne pollution with high metal contents. Baccharis trimera is popularly consumed as tea, and is widely developed in Candiota (Brazil), one of the most important coal burning regions of the Brazil. This study aims to investigate the phytochemical profile, in vivo genotoxic and mutagenic potential of extracts of B. trimera collected from an exposed region to pollutants generated by coal burning (Candiota City) and other unexposed region (Bagé City), using the Comet assay and micronucleus test in mice and the Salmonella/microsome short-term assay. The HPLC analyses indicated higher levels of flavonoids and phenolic acids for B. trimera aqueous extract from Bagé and absence of polycyclic aromatic hydrocarbons for both extracts. The presence of toxic elements such as cobalt, nickel and manganese was statistically superior in the extract from Candiota. For the Comet assay and micronucleus test, the mice were treated with Candiota and Bagé B. trimera aqueous extracts (500-2000 mg/kg). Significant genotoxicity was observed at higher doses treated with B. trimera aqueous extract from Candiota in liver and peripheral blood cells. Micronuclei were not observed but the results of the Salmonella/microsome short-term assay showed a significant increase in TA98 revertants for B. trimera aqueous extract from Candiota. The extract of B. trimera from Candiota bioacumulated higher levels of trace elements which were associated with the genotoxic effects detected in liver and peripheral blood cells.

  11. Chemical and toxicological effects of medicinal Baccharis trimera extract from coal burning area.

    PubMed

    Menezes, Ana Paula S; da Silva, Juliana; Fisher, Camila; da Silva, Fernanda R; Reyes, Juliana M; Picada, Jaqueline N; Ferraz, Alice G; Corrêa, Dione S; Premoli, Suziane M; Dias, Johnny F; de Souza, Claudia T; Ferraz, Alexandre de B F

    2016-03-01

    The entire process of power generation, extraction, processing and use of coal strongly impact water resources, soil, air quality and biota leads to changes in the fauna and flora. Pollutants generated by coal burning have been contaminating plants that grow in area impacted by airborne pollution with high metal contents. Baccharis trimera is popularly consumed as tea, and is widely developed in Candiota (Brazil), one of the most important coal burning regions of the Brazil. This study aims to investigate the phytochemical profile, in vivo genotoxic and mutagenic potential of extracts of B. trimera collected from an exposed region to pollutants generated by coal burning (Candiota City) and other unexposed region (Bagé City), using the Comet assay and micronucleus test in mice and the Salmonella/microsome short-term assay. The HPLC analyses indicated higher levels of flavonoids and phenolic acids for B. trimera aqueous extract from Bagé and absence of polycyclic aromatic hydrocarbons for both extracts. The presence of toxic elements such as cobalt, nickel and manganese was statistically superior in the extract from Candiota. For the Comet assay and micronucleus test, the mice were treated with Candiota and Bagé B. trimera aqueous extracts (500-2000 mg/kg). Significant genotoxicity was observed at higher doses treated with B. trimera aqueous extract from Candiota in liver and peripheral blood cells. Micronuclei were not observed but the results of the Salmonella/microsome short-term assay showed a significant increase in TA98 revertants for B. trimera aqueous extract from Candiota. The extract of B. trimera from Candiota bioacumulated higher levels of trace elements which were associated with the genotoxic effects detected in liver and peripheral blood cells. PMID:26741544

  12. Toxicological effects of copper oxide nanoparticles on the growth rate, photosynthetic pigment content, and cell morphology of the duckweed Landoltia punctata.

    PubMed

    Lalau, Cristina Moreira; Mohedano, Rodrigo de Almeida; Schmidt, Éder C; Bouzon, Zenilda L; Ouriques, Luciane C; dos Santos, Rodrigo W; da Costa, Cristina H; Vicentini, Denice S; Matias, William Gerson

    2015-01-01

    Recently, the application of copper oxide nanoparticles (CuO-NPs) has increased considerably, primarily in scientific and industrial fields. However, studies to assess their health risks and environmental impacts are scarce. Therefore, the present study aims to evaluate the toxicological effects of CuO-NPs on the duckweed species Landoltia punctata, which was used as a test organism. To accomplish this, duckweed was grown under standard procedures according to ISO DIS 20079 and exposed to three different concentrations of CuO-NPs (0.1, 1.0, and 10.0 g L(-1)), with one control group (without CuO-NPs). The toxicological effects were measured based on growth rate inhibition, changes in the plant's morphology, effects on ultrastructure, and alterations in photosynthetic pigments. The morphological and ultrastructural effects were evaluated by electronic, scanning and light microscopic analysis, and CuO-NPs were characterized using transmission electron microscopy (TEM), zeta potential, and superficial area methods of analysis. This analysis was performed to evaluate nanoparticle size and form in solution and sample stability. The results showed that CuO-NPs affected morphology more significantly than growth rate. L. punctata also showed the ability to remove copper ions. However, for this plant to be representative within the trophic chain, the biomagnification of effects must be assessed.

  13. Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

    PubMed

    Bauer, S; Wolff, I; Werner, N; Hoffmann, P; Herzschuh, R; Oemus, K; Rath, F W; Voigt, R

    1992-01-01

    In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased. PMID:1386950

  14. Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process

    SciTech Connect

    Bauer, S.; Wolff, I.; Werner, N.; Hoffmann, P.; Herzschuh, R.; Oemus, K.; Rath, F.W.; Voigt, R. )

    1992-05-01

    In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.

  15. Toxicological review of inorganic phosphates.

    PubMed

    Weiner, M L; Salminen, W F; Larson, P R; Barter, R A; Kranetz, J L; Simon, G S

    2001-08-01

    Inorganic phosphate salts are widely used as food ingredients and in a variety of commercial applications. The United States Food and Drug Administration (FDA) considers inorganic phosphates "Generally Recognized As Safe" (GRAS) (FDA, 1973a, 1979) [FDA: Food and Drug Administration 1973a. GRAS (Generally Recognized as Safe) food ingredients-phosphates. NTIS PB-221-224, FDA, Food and Drug Administration, 1979. Phosphates; Proposed Affirmation of and Deletion From GRAS Status as Direct and Human Food Ingredients. Federal Register 44 (244). 74845-74857, 18 December (1979)] and the European Union (EU) allows inorganic phosphates to be added directly to food (EU Directive 95/2/EC as amended by 98/72/EC). In this review, data on the acute, subchronic and chronic toxicity, genotoxicity, teratogenicity and reproductive toxicity from the published literature and from unpublished studies by the manufacturers are reviewed. Based on the toxicity data and similar chemistry, the inorganic phosphates can be separated into four major classes, consisting of monovalent salts, divalent salts, ammonium salts and aluminum salts. The proposed classification scheme supports the use of toxicity data from one compound to assess the toxicity of another compound in the same class. However, in the case of eye and skin irritation, the proposed classification scheme cannot be used because a wide range of responses exists within each class. Therefore, the eye and skin hazards associated with an individual inorganic phosphate should be assessed on a chemical-by-chemical basis. A large amount of toxicity data exists for all four classes of inorganic phosphates. The large and comprehensive database allows an accurate assessment of the toxicity of each class of inorganic phosphate. Overall, all four classes of inorganic phosphates exhibit low oral, inhalation and dermal toxicities. Based on these data, humans are unlikely to experience adverse effects when the daily phosphorus consumption remains

  16. Effects of an acute seizure on associative learning and memory.

    PubMed

    Holley, Andrew J; Lugo, Joaquin N

    2016-01-01

    Past studies have demonstrated that inducing several seizures or continuous seizures in neonatal or adult rats results in impairments in learning and memory. The impact of a single acute seizure on learning and memory has not been investigated in mice. In this study, we exposed adult 129SvEvTac mice to the inhalant flurothyl until a behavioral seizure was induced. Our study consisted of 4 experiments where we examined the effect of one seizure before or after delay fear conditioning. We also included a separate cohort of animals that was tested in the open field after a seizure to rule out changes in locomotor activity influencing the results of memory tests. Mice that had experienced a single seizure 1h, but not 6h, prior to training showed a significant impairment in associative conditioning to the conditioned stimulus when compared with controls 24h later. There were no differences in freezing one day later for animals that experienced a single seizure 1h after associative learning. We also found that an acute seizure reduced activity levels in an open-field test 2h but not 24h later. These findings suggest that an acute seizure occurring immediately before learning can have an effect on the recall of events occurring shortly after that seizure. In contrast, an acute seizure occurring shortly after learning appears to have little or no effect on long-term memory. These findings have implications for understanding the acute effects of seizures on the acquisition of new knowledge.

  17. Toxicologic interactions between ozone and bacterial endotoxin

    SciTech Connect

    Peavy, D.L.; Fairchild, E.J. II

    1987-02-01

    The effects of acute exposure of mice to bacterial lipopolysaccharide (LPS), the endotoxin of gram negative microorganisms, and ozone (O3) have been investigated. Intraperitoneal (ip) administration of 5 mg/kg LPS to CD-1 mice followed by exposure to 15 ppm O3 for 1.5 hr produced synergistic effects as measured by pulmonary edemagenesis and lethality assays. In contrast, ip administration of 0.1-1.6 mg/kg LPS to CD-1 mice over 5 consecutive days, a dose regimen resulting in LPS tolerance, protected against a lethal challenge of 20 ppm O3 for 3 hr. A statistically significant increase in catalase and glutathione peroxidase activity was measured in homogenates of lungs obtained from CD-1 mice receiving a tolerance-inducing regimen of LPS. These results demonstrate that two, distinct toxicologic interactions can occur between O3 and bacterial LPS. Synergism between these agents could explain, in part, the increased susceptibility of O3-exposed animals to respiratory infection with gram negative microorganisms. Protection resulting from LPS-induced increases in pulmonary antioxidant activity provides additional evidence that O3 and, possibly, LPS mediate their toxicity through oxidative mechanisms.

  18. Role of toxicological interactions in lung injury

    SciTech Connect

    Witschi, H.P.; Hakkinen, P.J.

    1984-04-01

    Interactions between two or more toxic agents can produce lung damage by chemical-chemical interactions, chemical-receptor interactions or by modification, by a first agent, of the cell and tissue response to a second agent. Interactions may occur by simultaneous exposure and if exposure to two agents is separated in time. Chemical-chemical interactions have been mostly studied in the toxicology of air pollutants, where it was shown that the untoward effect of certain oxidants may be enhanced in the presence of other aerosols. Interactions at the receptor site have been found in isolated perfused lung experiments. Oxygen tolerance may be an example, when pre-exposure to one concentration of oxygen mitigates later exposure to 100% oxygen by modifying cellular and enzymatic composition of the lung. Damage of the alveolar zone by the antioxidant butylated hydroxytoluene (BHT) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents. 121 references.

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

    PubMed Central

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

    2013-01-01

    The aim of the current study is to evaluate the effect of andrographolide on hyperlipidemia induced by Porphyromonas gingivalis in rats. Thirty male Sprague Dawley (SD) rats were divided into five groups as follows: group 1 (vehicle) and four experimental groups (groups 2, 3, 4, and 5) were challenged orally with P. gingivalis ATCC 33277 (0.2 mL of 1.5 ×1012 bacterial cells/mL in 2% carboxymethylcellulose (CMC) with phosphate-buffered saline (PBS)) five times a week for one month to induce hyperlipidemia. Then, group 3 received a standard oral treatment with simvastatin 100 mg/kg, and groups 4 and 5 received oral treatment with andrographolide 20 mg/kg and 10 mg/kg, respectively, for another month. The results showed that total cholesterol (TC), low-density lipoprotein (LDL-C), and triglycerides (TG) were reduced significantly in groups treated with andrographolide. The malondialdehyde (MDA) level was low in treated groups, while antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly increased in these groups (P < 0.05). Liver tissues of the groups treated with andrographolide reduce the accumulation of lipid droplets in hepatic tissue cells. An acute toxicity test did not show any toxicological symptoms in rats. PMID:23844365

  20. Cord Blood Cells for Developmental Toxicology and Environmental Health

    PubMed Central

    Il’yasova, Dora; Kloc, Noreen; Kinev, Alexander

    2015-01-01

    The Tox21 program initiated a shift in toxicology toward in vitro testing with a focus on the biological mechanisms responsible for toxicological response. We discuss the applications of these initiatives to developmental toxicology. Specifically, we briefly review current approaches that are widely used in developmental toxicology to demonstrate the gap in relevance to human populations. An important aspect of human relevance is the wide variability of cellular responses to toxicants. We discuss how this gap can be addressed by using cells isolated from umbilical cord blood, an entirely non-invasive source of fetal/newborn cells. Extension of toxicological testing to collections of human fetal/newborn cells would be useful for better understanding the effect of toxicants on fetal development in human populations. By presenting this perspective, we aim to initiate a discussion about the use of cord blood donor-specific cells to capture the variability of cellular toxicological responses during this vulnerable stage of human development. PMID:26697419

  1. Advancing Risk Assessment through the Application of Systems Toxicology.

    PubMed

    Sauer, John Michael; Kleensang, André; Peitsch, Manuel C; Hayes, A Wallace

    2016-01-01

    Risk assessment is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. Mechanistic approaches to risk assessment have been generally referred to as systems toxicology. Systems toxicology makes use of advanced analytical and computational tools to integrate classical toxicology and quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Three presentations including two case studies involving both in vitro and in vivo approaches described the current state of systems toxicology and the potential for its future application in chemical risk assessment. PMID:26977253

  2. Advancing Risk Assessment through the Application of Systems Toxicology

    PubMed Central

    Sauer, John Michael; Kleensang, André; Peitsch, Manuel C.; Hayes, A. Wallace

    2016-01-01

    Risk assessment is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. Mechanistic approaches to risk assessment have been generally referred to as systems toxicology. Systems toxicology makes use of advanced analytical and computational tools to integrate classical toxicology and quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Three presentations including two case studies involving both in vitro and in vivo approaches described the current state of systems toxicology and the potential for its future application in chemical risk assessment. PMID:26977253

  3. Review, discussion, and summary: toxicology.

    PubMed

    Graham, J A

    1989-02-01

    The research presented in the toxicology session of the Symposium on the Health Effects of Acid Aerosols significantly advances our understanding of the health effects of acid aerosols and clearly illustrates the importance of animal inhalation toxicology to risk assessment. The description of the effects of acid on airway mucus buffering capacity and viscosity helps explain some of the mechanisms responsible for the effects of sulfuric acid on mucociliary clearance and pulmonary function observed in man and animals. Several of the papers illustrate that other pollutants interact with sulfuric acid (H2SO4), causing concern about exposure risks and helping in elucidating the effects observed in epidemiology studies that have not yet been duplicated in a laboratory. For example, H2SO4 absorbed in zinc oxide (ZnO) particles appears to be about a log more potent than H2SO4 alone in causing pulmonary function decrements. Low levels of H2SO4 and O3 were found to be synergistic in increasing collagen synthesis, implying a risk in development of lung fibrosis. More complex mixtures containing H2SO4 cause a variety of interactions, depending upon the end points examined and the chemistry of the mixture. Other reports indicate that dose rate and length of exposure issues are critical to toxicological outcomes. Animal data on mucociliary clearance, which parallels that of human data, was extended to show that concentration of exposure was more important than time of exposure in eliciting a response, although time played a significant role. A recent chronic study showed that H2SO4 caused effects that also can occur in the development of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Toxicological and biochemical studies on Schinus terebinthifolius concerning its curative and hepatoprotective effects against carbon tetrachloride-induced liver injury

    PubMed Central

    Abdou, Rania H.; Saleh, Sherif Y.; Khalil, Waleed F.

    2015-01-01

    Background: Recently, many efforts have been made to discover new products of natural origin which can limit the xenobiotic-induced hepatic injury. Carbon tetrachloride (CCl4) is a highly toxic chemical that is widely used to study hepatotoxicity in animal models. Objective: The present study was conducted to investigate the curative and protective effects of Schinus terbenthifolius ethanolic extract against CCl4 -induced acute hepatotoxicity in rats. Materials and Methods: S. terbenthifolius extract was orally administered in a dose of 350 mg dried extract/kg b.wt. before and after intoxication with CCl4 for curative and protective experiments, respectively. A group of hepatotoxicity indicative enzymes, oxidant-antioxidant capacity, DNA oxidation, and apoptosis markers were measured. Results: CCl4 increased liver enzyme leakage, oxidative stress, hepatic apoptosis, DNA oxidation, and inflammatory markers. Administration of S. terebinthifolius, either before or after CCl4 intoxication, significantly decreased elevated serum liver enzymes and reinstated the antioxidant capacity. Interestingly, S. terebinthifolius extract inhibited hepatocyte apoptosis as revealed by approximately 20 times down-regulation in caspase-3 expression when compared to CCl4 untreated group. On the other hand, there was neither protective nor curative effect of S. terebinthifolius against DNA damage caused by CCl4. Conclusion: The present study suggests that S. terebinthifolius extract could be a substantially promising hepatoprotective agent against CCl4 toxic effects and may be against other hepatotoxic chemical or drugs. PMID:26109780

  5. 40 CFR 158.230 - Experimental use permit data requirements for toxicology.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Experimental use permit data requirements for toxicology. All toxicology data, as described in paragraph (c) of.... CR=Conditionally required; NR=Not required; R=Required; EP=End-use product; MP=Manufacturing-use... neurotoxicity (acute) - hen CR CR TGAI TGAI 5 Subchronic Testing 870.3100 90-day Oral - rodent R NR TGAI...

  6. A medical-toxicological view of tattooing.

    PubMed

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta; Blume, Annegret; Al Dahouk, Sascha; Bäumler, Wolfgang; Bernstein, Eric; Bocca, Beatrice; Alimonti, Alessandro; Colebrook, Helen; de Cuyper, Christa; Dähne, Lars; Hauri, Urs; Howard, Paul C; Janssen, Paul; Katz, Linda; Klitzman, Bruce; Kluger, Nicolas; Krutak, Lars; Platzek, Thomas; Scott-Lang, Victoria; Serup, Jørgen; Teubner, Wera; Schreiver, Ines; Wilkniß, Elena; Luch, Andreas

    2016-01-23

    Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing.

  7. A medical-toxicological view of tattooing.

    PubMed

    Laux, Peter; Tralau, Tewes; Tentschert, Jutta; Blume, Annegret; Al Dahouk, Sascha; Bäumler, Wolfgang; Bernstein, Eric; Bocca, Beatrice; Alimonti, Alessandro; Colebrook, Helen; de Cuyper, Christa; Dähne, Lars; Hauri, Urs; Howard, Paul C; Janssen, Paul; Katz, Linda; Klitzman, Bruce; Kluger, Nicolas; Krutak, Lars; Platzek, Thomas; Scott-Lang, Victoria; Serup, Jørgen; Teubner, Wera; Schreiver, Ines; Wilkniß, Elena; Luch, Andreas

    2016-01-23

    Long perceived as a form of exotic self-expression in some social fringe groups, tattoos have left their maverick image behind and become mainstream, particularly for young people. Historically, tattoo-related health and safety regulations have focused on rules of hygiene and prevention of infections. Meanwhile, the increasing popularity of tattooing has led to the development of many new colours, allowing tattoos to be more spectacular than ever before. However, little is known about the toxicological risks of the ingredients used. For risk assessment, safe intradermal application of these pigments needs data for toxicity and biokinetics and increased knowledge about the removal of tattoos. Other concerns are the potential for phototoxicity, substance migration, and the possible metabolic conversion of tattoo ink ingredients into toxic substances. Similar considerations apply to cleavage products that are formed during laser-assisted tattoo removal. In this Review, we summarise the issues of concern, putting them into context, and provide perspectives for the assessment of the acute and chronic health effects associated with tattooing. PMID:26211826

  8. Occupational toxicology of nickel and nickel compounds.

    PubMed

    Zhao, Jinshun; Shi, Xianglin; Castranova, Vincent; Ding, Min

    2009-01-01

    Nickel and nickel compounds are widely used in industry. The high consumption of nickel products inevitably leads to occupational and environmental pollution. In occupational settings, exposure to nickel and nickel compounds occurs primarily during nickel refining, electroplating, and welding. The most common airborne exposures to nickel in the workplace are to insoluble nickel species, such as metallic nickel, nickel sulfide, and nickel oxides from dusts and fumes. The chemical and physical properties of nickel and nickel compounds strongly influence their bioavailability and toxicity. The lung and the skin are the principal target organs upon occupational exposure. inhalation exposure is a primary route for nickel-induced toxicity in the workplace. The most important adverse health effects due to occupational exposure to nickel and its compounds are skin allergies, lung fibrosis, and lung cancer. The exact mechanisms of nickel-induced carcinogenesis are not clear. This review summarizes the current knowledge on occupational toxicology of nickel and its compounds. The subtopics include: chemical and physical properties, uses, occupational exposures, occupational exposure limits, toxicokinetics, biological monitoring, acute toxicity, chronic toxicity, genotoxicity, reproductive toxicity, carcinogenicity, molecular mechanisms of carcinogenesis, and gaps in knowledge. PMID:19888907

  9. Water quality criteria/toxicological benchmarks for nitroaromatic munitions compounds

    SciTech Connect

    Talmage, S.S.; Opresko, D.M.; Hovatter, P.S.; Daniel, F.B.

    1995-12-31

    There is a need to develop screening level and cleanup criteria for nitroaromatic compounds at US Army Superfund sites. Using available methodologies, Water Quality Criteria (WQC) for aquatic organisms and toxicological benchmarks for terrestrial plants and wildlife were developed for eight nitroaromatic munitions compounds and/or their degradation products: 2,4,6-trinitroluene, 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, 3,5-dinitroaniline, 2-amino-4, 6-dinitrotoluene, RDX, HMX, and tetryl. Depending on available data, acute and chronic WQC for aquatic species were developed based on US EPA Tier 1 or Tier 2 guidelines. Criteria for sediment-associated organisms were derived based on Equilibrium Partitioning. In the absence of criteria or guidance for effects on terrestrial wildlife, plants and soil processes, ecotoxicological benchmarks, i.e., NOAELs and LOECs for effects on these organisms were identified. Benchmarks for terrestrial wildlife species were derived from experimental data identifying toxicological endpoints for wildlife or laboratory species. NOAELs were based on endpoints of population growth and survival following oral exposures. These values were used as the basis for calculation of NOAELs or screening benchmarks for food and water intake for seven selected mammalian wildlife species: the short-tailed shrew, white footed mouse, meadow vole, cottontail rabbit, mink, red fox, and whitetail deer. Equivalent NOAELs were calculated by scaling the test data on the basis of differences in body weight. Benchmarks for terrestrial plants and soil invertebrates and heterotrophic processes were based on LOECs.

  10. American College of Medical Toxicology

    MedlinePlus

    ... NACCT Board Review Course Chemical Agents of Opportunity: TICs and TIMs Seminars in Forensic Toxicology Clandestine Meth ... City Center Reservations 2016 Chemical Agents of Opportunity: TICs and TIMs Syllabus Seminars in Forensic Toxicology 2013 ...

  11. Acute pulmonary effects of ultrafine particles in rats and mice.

    PubMed

    Oberdörster, G; Finkelstein, J N; Johnston, C; Gelein, R; Cox, C; Baggs, R; Elder, A C

    2000-08-01

    Ambient fine particles consist of ultrafine particles (< 100 nm) and accumulation-mode particles (approximately 100 to 1,000 nm). Our hypothesis that ultrafine particles can have adverse effects in humans is based on results of our earlier studies with particles of both sizes and on the finding that urban ultrafine particles can reach mass concentrations of 40 to 50 micrograms/m3, equivalent to number concentrations of 3 to 4 x 10(5) particles/cm3. The objectives of the exploratory studies reported here were to (1) evaluate pulmonary effects induced in rats and mice by ultrafine particles of known high toxicity (although not occurring in the ambient atmosphere) in order to obtain information on principles of ultrafine particle toxicology; (2) characterize the generation and coagulation behavior of ultrafine particles that are relevant for urban air; (3) study the influence of animals' age and disease status; and (4) evaluate copollutants as modifying factors. We used ultrafine Teflon (polytetrafluoroethylene [PTFE]*) fumes (count median diameter [CMD] approximately 18 nm) generated by heating Teflon in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity that might be helpful in understanding potential effects of ambient ultrafine particles. Teflon fumes at ultrafine particle concentrations of approximately 50 micrograms/m3 are extremely toxic to rats when inhaled for only 15 minutes. We found that neither the ultrafine Teflon particles alone when generated in argon nor the Teflon fume gas-phase constituents when generated in air were toxic after 25 minutes of exposure. Only the combination of both phases when generated in air caused high toxicity, suggesting the existence of either radicals on the particle surface or a carrier mechanism of the ultrafine particles for adsorbed gas-phase compounds. We also found rapid translocation of the ultrafine Teflon particles across the epithelium after their deposition, which appears to be an

  12. Oral-toxicology

    PubMed Central

    Gowda, B. K. Charan; Sundharam, B. Sivapatha; Mahadesh, Jyothi; Mukund

    2014-01-01

    Forensic toxicology deals with the investigation of toxic substances, poisonous products or with the environmental chemicals. This field of science helps to identify poison substance and hazardous chemicals. Forensic toxicology deals with the way that substances are absorbed, distributed or eliminated in the body – the metabolism of substances. This paper reviews the manifestations that each poisonous substance presents concentrating toward the commonly used poisonous substance especially in India. It also explains the Indian Penal Code, which is main criminal code intended to cover all substantive aspects of criminal law regarding poison. PMID:24696586

  13. Shuttle Lesson Learned - Toxicology

    NASA Technical Reports Server (NTRS)

    James, John T.

    2010-01-01

    This is a script for a video about toxicology and the space shuttle. The first segment is deals with dust in the space vehicle. The next segment will be about archival samples. Then we'll look at real time on-board analyzers that give us a lot of capability in terms of monitoring for combustion products and the ability to monitor volatile organics on the station. Finally we will look at other issues that are about setting limits and dealing with ground based lessons that pertain to toxicology.

  14. National Particle Component Toxicity (NPACT) Initiative: integrated epidemiologic and toxicologic studies of the health effects of particulate matter components.

    PubMed

    Lippmann, Morton; Chen, Lung-Chi; Gordon, Terry; Ito, Kazuhiko; Thurston, George D

    2013-10-01

    identify their sources and their roles in eliciting both short- and long-term health-related responses. In addition, from the same five air-sheds we collected samples of coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles. Aliquots of these samples were administered to cells in vitro and to mouse lungs in vivo (by aspiration) in order to determine their comparative acute effects (Gordon Study). The results of these four complementary studies, and the overall integrative analyses, provide a basis for guiding future research and for helping to determine more targeted emission controls for the PM components most hazardous to acute and chronic health. Application of the knowledge gained in this work may therefore contribute to an optimization of the public health benefits of future PM emission controls. The design of each NPACT study conducted at NYU was guided by our scientific hypotheses, which were based on our reviews of the background literature and our experience in conducting studies of associations between ambient PM and health-related responses. These hypotheses guided the development and conduct of the four studies. Hypothesis 1. Coarse, fine, and ultrafine PM are each capable of producing acute health effects of public health concern, but the effects may differ according to particle size and composition. (Applies to all studies.) Hypothesis 2. Long-term PM2.5 exposures are closely associated with chronic health effects. (Applies to studies 1 and 4.) Hypothesis 3. The source-apportionment techniques that we have developed and refined in recent years provide a useful basis for identifying major categories of sources of PM in ambient air and specific chemical components that have the greatest impacts on a variety of acute and chronic health effects. (Applies to all studies.) Hypothesis 4. The health effects due to ambient PM exposures can best be seen in sensitive subgroups within overall human populations and in animal models of such populations

  15. Acute and subchronic toxic effects of atrazine and chlorpyrifos on common carp (Cyprinus carpio L.): Immunotoxicity assessments.

    PubMed

    Xing, Houjuan; Liu, Tao; Zhang, Ziwei; Wang, Xiaolong; Xu, Shiwen

    2015-08-01

    Atrazine (ATR) and chlorpyrifos (CPF) are widely used pesticides in agricultural practices throughout world. It has resulted in a series of toxicological and environmental problems, such as impacts on many non-target aquatic species, including fish. The spleen and head kidney in the bony fish are the major hematopoietic organs, and play a crucial part in immune responses. This study evaluated the subchronic effects of ATR and CPF on the mRNA and protein levels of HSP60, HSP70 and HSP90 in the immune organs of common carp and compared the acute and subchronic effects of ATR and CPF on the swimming speed (SS) of common carp. The results of acute toxicity tests showed that the 96 h-LC50 of ATR and CPF for common carp was determined to be 2.142 and 0.582 mg/L, respectively. Meanwhile, acute and subacute toxicity of ATR and CPF in common carp resulted in hypoactivity. We also found that the mRNA and protein levels of HSP60, HSP70 and HSP90 genes were induced in the spleen and head kidney of common carp exposed to ATR and CPF in the subchronic toxicity test. Our results indicate that ATR and CPF are highly toxic to common carp, and hypoactivity in common carp by acute and subchronic toxicity of ATR and CPF may provide a useful tool for assessing the toxicity of triazine herbicide and organophosphorous pesticides to aquatic organisms. In addition, the results from the subchronic toxicity test exhibited that increasing concentration of ATR and CPF in the environment causes considerable stress for common carp, suggesting that ATR and CPF exposure cause immunotoxicity to common carp.

  16. Toxicology of chlorofluorocarbon replacements.

    PubMed Central

    Dekant, W

    1996-01-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements. PMID:8722112

  17. Toxicology of chlorofluorocarbon replacements.

    PubMed

    Dekant, W

    1996-03-01

    Chlorofluorocarbons (CFCs) are stable in the atmosphere and may reach the stratosphere. They are cleaved by UV-radiation in the stratosphere to yield chlorine radicals, which are thought to interfere with the catalytic cycle of ozone formation and destruction and deplete stratospheric ozone concentrations. Due to potential adverse health effects of ozone depletion, chlorofluorocarbon replacements with much lower or absent ozone depleting potential are developed. The toxicology of these compounds that represent chlorofluorohydrocarbons (HCFCs) or fluorohydrocarbons (HFCs) has been intensively studied. All compounds investigated (1, 1-dichloro-1-fluoroethane [HCFC-141b], 1,1,1,2-tetrafluoroethane [HFC-134a], pentafluoroethane [HFC-125], 1-chloro- 1,2,2,2-tetrafluoroethane [HCFC-124], and 1,1-dichloro-2,2,2-trifluoroethane [HCFC-123]) show only a low potential for skin and eye irritation. Chronic adverse effects on the liver (HCFC-123) and the testes (HCFC-141b and HCFC-134a), including tumor formation, were observed in long-term inhalation studies in rodents using very high concentrations of these CFC replacements. All CFC replacements are, to varying extents, biotransformed in the organism, mainly by cytochrome P450-catalyzed oxidation of C-H bonds. The formed acyl halides are hydrolyzed to give excretable carboxylic acids; halogenated aldehydes that are formed may be further oxidized to halogenated carboxylic acids or reduced to halogenated alcohols, which are excretory metabolites in urine from rodents exposed experimentally to CFC replacements. The chronic toxicity of the CFC replacements studied is unlikely to be of relevance for humans exposed during production and application of CFC replacements.

  18. Effects of Acute Exercise on Long-Term Memory

    ERIC Educational Resources Information Center

    Labban, Jeffrey D.; Etnier, Jennifer L.

    2011-01-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of…

  19. Acute Stressor Effects on Goal-Directed Action in Rats

    ERIC Educational Resources Information Center

    Braun, Stephanie; Hauber, Wolfgang

    2013-01-01

    Here we examined effects of acute stressors that involve either systemic coadministration of corticosterone/yohimbine (3 mg/kg each) to increase glucocorticoid/noradrenaline activity (denoted as "pharmacological" stressor) or one or several distinct restraint stressors (denoted as "single" vs. "multiple" stressor) on…

  20. Is racecadotril effective for acute diarrhea in children? -First update.

    PubMed

    Sáez, Josefina; Cifuentes, Lorena

    2016-05-06

    This article updates the December 2015 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos), based on the detection of two systematic reviews not identified in the previous version. Gastroenteritis or acute watery diarrhea is usually a self-limited disease, but it is still associated to substantial healthcare costs and remains a frequent demand for medical care. Racecadotril, an intestinal enkephalinase inhibitor, has been used as treatment because it would decrease the duration of acute diarrhea and fluid loss. However there is still no evidence supporting its routine use. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including nine randomized trials relevant for our question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded racecadotril probably reduces the duration of acute diarrhea in pediatric patients, without increasing adverse effects.

  1. Is racecadotril effective for acute diarrhea in children? -First update.

    PubMed

    Sáez, Josefina; Cifuentes, Lorena

    2016-01-01

    This article updates the December 2015 Living FRISBEE (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos), based on the detection of two systematic reviews not identified in the previous version. Gastroenteritis or acute watery diarrhea is usually a self-limited disease, but it is still associated to substantial healthcare costs and remains a frequent demand for medical care. Racecadotril, an intestinal enkephalinase inhibitor, has been used as treatment because it would decrease the duration of acute diarrhea and fluid loss. However there is still no evidence supporting its routine use. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including nine randomized trials relevant for our question. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded racecadotril probably reduces the duration of acute diarrhea in pediatric patients, without increasing adverse effects. PMID:26731112

  2. Nanosilver: application and novel aspects of toxicology.

    PubMed

    Schluesener, Jan K; Schluesener, Hermann J

    2013-04-01

    Nanomaterials are a challenge to toxicology. The high diversity of novel materials and products will require extensive expertize for evaluation and regulatory efforts. Nanomaterials are of substantial scientific and economic potential. Here, we will focus on nanosilver, a material not only with medical applications, but a rapidly increasing use in surprisingly many products. Consequently, toxicological evaluation has to cover an increasing range of complex topics. The toxicology of nanosilver is advancing rapidly; regulatory efforts by Federal Drug Agency and European Environment Protection Agencies are substantial. Current toxicological data, ranging from in vitro studies with cell lines to rodent experiments and ecological evaluation, are numerous, and many groups are providing continuously new data. However, standard classification based on nanosize only is neglecting nanoshape, which adds another level of complexity to the analysis of biological effects. A surprising neglect in nanosilver toxicology so far is the analysis of effects of nanosilver on amyloidosis. Amyloid diseases are widespread in humans and a severe health hazard. The known potential of silver to stimulate amyloidosis in rodents will require a timely and balanced evaluation of nanosilvers.

  3. Evaluation of potential health effects of 10 kHz magnetic fields: A short-term mouse toxicology study

    SciTech Connect

    Robertson, I.G.C.; Wilson, W.R.; Dawson, B.V.; Zwi, L.J.; Green, A.W.; Boys, J.T.

    1996-05-01

    A high-frequency inductive power distribution (HID) technology has been developed that generates sinusoidal magnetic fields at a frequency of 10 kHz. In typical industrial applications, field intensities in the order of 0.2 mT can be expected between the current-carrying coils. Because the possible health effects of 10 kHz sinusoidal magnetic fields of this type had never been investigated, a broad evaluation of possible effects on animal health was made in a preliminary 14 day acute study and in a 90 day subchromic study using male and female B6C3F1 mice. Exposures were at 0.08, 0.28, and 1.0 mT vs a background exposure of 3.7 {micro}T and were essentially continuous. These studies failed to demonstrate any health effects that can be clearly related to the magnetic field exposure. No changes in animal behavior or indications of morbidity were detected during the initial exposure to the fields. There were no significant differences in body weight between exposed and unexposed (control) mice at any time int h study, and the clinical chemistry and hematology parameters were essentially unchanged. Although minor differences in some clinical chemistry and hematology parameters were seen between control and exposure groups, the lack of exposure dependence, the lack of consistency between sexes, and the lack of correspondence with the results of the two studies all suggest that these were chance associations. Even if the changes were real, the magnitude of the changes was very small and does not indicate serious biological effects. Finally, all organs were macroscopically and microscopically normal except for isolated, generally mild, histological lesions and lesions that were ascribed to fighting among males. There was no obvious association with field intensity.

  4. Toxicology, an STS Approach.

    ERIC Educational Resources Information Center

    Wagner, Richard

    1990-01-01

    Presented are activities suggested through Project L.A.B.S. that involve the topic of toxicology. Activities include suggested research, the risk benefit seesaw, human-made compounds, legislation, a historical perspective, and health. A suggested readings list is provided. (KR)

  5. Acute Achilles tendinopathy: effect of pain control on leg stiffness.

    PubMed

    Maquirriain, J; Kokalj, A

    2014-03-01

    Tendinopathies are a major cause of disability in the athletic population; the main purpose of the treatment of these injuries is to reduce pain and improve function. The aim of this study was to evaluate the effect of NSAIDs on leg stiffness of patients suffering acute unilateral Achilles tendinopathy. Twenty-eight eligible male athletes (aged 39.1 ± 10.3 y) suffering acute Achilles tendinopathy were treated with etoricoxib (120 mg oral once daily) during 7 days. Pain (100-mm visual analogue scale-VAS), analgesic effect (percentage of 100-mm VAS reduction), and leg stiffness were evaluated pre- and post- anti-inflammatory treatment. Results of this study showed that over the 7-day treatment period, etoricoxib provided significant relief of Achilles tendon pain (VAS) compared to that experienced at baseline: 54.5 ± 21.6 and 24.5 ± 24.8, respectively (p<0.001). Leg stiffness showed a significant improvement after one-week NSAID therapy: LSR 0.89 ± 0.1 vs. 0.97 ± 0.1; (p=0.02). In conclusion, findings of this study demonstrated that patients suffering acute unilateral Achilles tendinopathy increased their leg stiffness of the affected side after oral anti-inflammatory therapy. Effective control of tendon pain in the acute phase of such sports-related injuries may contribute to improve capabilities associated with high performance like leg stiffness. PMID:24583548

  6. Toxicological benchmarks for wildlife: 1996 Revision

    SciTech Connect

    Sample, B.E.; Opresko, D.M.; Suter, G.W., II

    1996-06-01

    The purpose of this report is to present toxicological benchmarks for assessment of effects of certain chemicals on mammalian and avian wildlife species. Publication of this document meets a milestone for the Environmental Restoration (ER) Risk Assessment Program. This document provides the ER Program with toxicological benchmarks that may be used as comparative tools in screening assessments as well as lines of evidence to support or refute the presence of ecological effects in ecological risk assessments. The chemicals considered in this report are some that occur at US DOE waste sites, and the wildlife species evaluated herein were chosen because they represent a range of body sizes and diets.

  7. The influence of salinity on toxicological effects of arsenic in digestive gland of clam Ruditapes philippinarum using metabolomics

    NASA Astrophysics Data System (ADS)

    Ji, Chenglong; Wu, Huifeng; Liu, Xiaoli; Zhao, Jianmin; Yu, Junbao; Yin, Xiuli

    2013-03-01

    Ruditapes philippinarum, a clam that thrives in intertidal zones of various salinities, is a useful biomonitor to marine contaminants. We investigated the influence of dilution to 75% and 50% of normal seawater salinity (31.1) on the responses of the digestive gland of R. philippinarum to arsenic exposure (20 μg/L), using nuclear magnetic resonance (NMR)-based metabolomics. After acute arsenic exposure for 48 h, salinity-dependent differential metabolic responses were detected. In normal seawater, arsenic exposure increased the concentrations of branched-chain amino acids, and of threonine, proline, phosphocholine and adenosine, and it decreased the levels of alanine, hypotaurine, glucose, glycogen and ATP in the digestive glands. Differential changes in metabolic biomarkers observed at lower salinity (˜23.3) included elevation of succinate, taurine and ATP, and depletion of branched-chain amino acids, threonine and glutamine. Unique effects of arsenic at the lowest salinity (˜15.6) included down-regulation of glutamate, succinate and ADP, and up-regulation of phosphocholine. We conclude that salinity influences the metabolic responses of this clam to arsenic.

  8. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 2-HEXANONE

    EPA Science Inventory

    EPA will conduct an assessment of the noncancer health effects of 2-hexanone. The IRIS program will prepare an IRIS assessment for 2-hexanone. The IRIS assessment for 2-hexanone will consist of a Toxicological Review and an IRIS Summary. The Toxicological Review is a critical ...

  9. Acute effects of tea consumption on attention and mood.

    PubMed

    Einöther, Suzanne J; Martens, Vanessa E

    2013-12-01

    Tea has historically been associated with mood and performance benefits, such as relaxation and concentration. This review summarizes the research on the acute effects of tea, and its ingredients theanine and caffeine, on attention and mood. Consistent with abundant research on the benefits of caffeine, the performance benefits of tea were identified in a number of studies, with particularly consistent evidence for improved attention. Tea consumption also consistently improved self-reported alertness and arousal, whereas effects on pleasure or relaxation were less consistent. In addition to the research on caffeine in real-life performance, 2 recent studies have provided a broader perspective on tea's effects on psychological function in that they showed beneficial effects in related areas such as work performance and creativity. These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.

  10. Toxicological profile for polycyclic aromatic hydrocarbons. Final report

    SciTech Connect

    Not Available

    1990-12-01

    The ATSDR Toxicological Profile for Polycyclic Aromatic Hydrocarbons (PAHs): Acenaphthene, Acenaphthylene, Anthracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,h,i)perylene, Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene, Indeno(1,2,3-cd)pyrene, Phenanthrene, Pyrene is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information.

  11. Toxicological benchmarks for potential contaminants of concern for effects on soil and litter invertebrates and heterotrophic process

    SciTech Connect

    Will, M.E.; Suter, G.W. II

    1995-09-01

    An important step in ecological risk assessments is screening the chemicals occur-ring on a site for contaminants of potential concern. Screening may be accomplished by comparing reported ambient concentrations to a set of toxicological benchmarks. Multiple endpoints for assessing risks posed by soil-borne contaminants to organisms directly impacted by them have been established. This report presents benchmarks for soil invertebrates and microbial processes and addresses only chemicals found at United States Department of Energy (DOE) sites. No benchmarks for pesticides are presented. After discussing methods, this report presents the results of the literature review and benchmark derivation for toxicity to earthworms (Sect. 3), heterotrophic microbes and their processes (Sect. 4), and other invertebrates (Sect. 5). The final sections compare the benchmarks to other criteria and background and draw conclusions concerning the utility of the benchmarks.

  12. Emerging Approaches in Predictive Toxicology

    PubMed Central

    Zhang, Luoping; McHale, Cliona M.; Greene, Nigel; Snyder, Ronald D.; Rich, Ivan N.; Aardema, Marilyn J.; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

    2016-01-01

    Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. PMID:25044351

  13. Teaching Toxicology as a Basic Medical Science

    ERIC Educational Resources Information Center

    Gralla, Edward J.

    1976-01-01

    A 4-year effort at Yale University School of Medicine to teach toxicology as an elective basic science from the standpoint of organ-specific toxic effects is described. The objective of the successful multidisciplinary program is to prepare physicians to understand, recognize, and manage adverse effects from drugs and other environmental…

  14. Toxicologic methods: controlled human exposures.

    PubMed Central

    Utell, M J; Frampton, M W

    2000-01-01

    The assessment of risk from exposure to environmental air pollutants is complex, and involves the disciplines of epidemiology, animal toxicology, and human inhalation studies. Controlled, quantitative studies of exposed humans help determine health-related effects that result from breathing the atmosphere. The major unique feature of the clinical study is the ability to select, control, and quantify pollutant exposures of subjects of known clinical status, and determine their effects under ideal experimental conditions. The choice of outcomes to be assessed in human clinical studies can be guided by both scientific and practical considerations, but the diversity of human responses and responsiveness must be considered. Subjects considered to be among the most susceptible include those with asthma, chronic obstructive lung disease, and cardiovascular disease. New experimental approaches include exposures to concentrated ambient air particles, diesel engine exhaust, combustion products from smoking machines, and experimental model particles. Future investigations of the health effects of air pollution will benefit from collaborative efforts among the disciplines of epidemiology, animal toxicology, and human clinical studies. PMID:10931779

  15. Reviews of environmental contamination and toxicology

    SciTech Connect

    Ware, G.

    2007-07-01

    Review of Environmental Contamination and Toxicology attempts to provide concise, critical reviews of timely advances, philosophy and significant areas of accomplished or needed endeavour in the total field of xenobiotics, in any segment of the environment, as well as toxicological implications. This edition contains a paper 'Health effects of arsenic, fluorine and selenium from indoor burning of Chinese coal, by Liu Guijian, Zheng Liugen, Nurdan S. Duzgoren-Aydin, Gao Lianfen, Liu Junhua, and Peng Zicheng. Other papers are: Chemistry and fate of simazine; Ethanol production: energy, economic, and environmental losses; Arsenic behaviour from groundwater and soil to crops: impacts on agriculture and food safety; Mercury content of hair in different populations relative to fish consumption; and Toxicology of 1,3-butadiene, chloroprene, and isoprene. 15 ills.

  16. The effects of acute and chronic stress on diabetes control.

    PubMed

    Marcovecchio, M Loredana; Chiarelli, Francesco

    2012-10-23

    Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood glucose concentrations in patients with type 1 and type 2 diabetes. The effect of stress on glycemic control in people with diabetes may be related to a direct effect of stress hormones on blood glucose levels and an indirect effect of stress on patient behaviors related to diabetes treatment and monitoring and meal and exercise plans. In contrast, there is no clear evidence that stressful life events promote the development of diabetes in children or in adults. Stress hyperglycemia, the development of hyperglycemia during acute illness, represents another interesting connection between the stress system and glucose homeostasis. A large body of evidence supports an association between stress hyperglycemia and increased morbidity and mortality in critically ill patients. Interestingly, there is some evidence supporting a beneficial effect of insulin in reducing morbidity and mortality in patients admitted to intensive care units. Finally, stress can influence the development of type 2 diabetes indirectly by promoting obesity and metabolic syndrome. PMID:23092890

  17. Effect of acute and fractionated irradiation on hippocampal neurogenesis.

    PubMed

    Park, Min-Kyoung; Kim, Seolhwa; Jung, Uhee; Kim, Insub; Kim, Jin Kyu; Roh, Changhyun

    2012-08-08

    Ionizing radiation has become an inevitable health concern emanating from natural sources like space travel and from artificial sources like medical therapies. In general, exposure to ionizing radiation such as γ-rays is one of the methods currently used to stress specific model systems. In this study, we elucidated the long-term effect of acute and fractionated irradiation on DCX-positive cells in hippocampal neurogenesis. Groups of two-month-old C57BL/6 female mice were exposed to whole-body irradiation at acute dose (5 Gy) or fractional doses (1 Gy × 5 times and 0.5 Gy × 10 times). Six months after exposure to γ-irradiation, the hippocampus was analyzed. Doublecortin (DCX) immunohistochemistry was used to measure changes of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). The number of DCX-positive cells was significantly decreased in all acute and fractionally irradiation groups. The long-term changes in DCX-positive cells triggered by radiation exposure showed a very different pattern to the short-term changes which tended to return to the control level in previous studies. Furthermore, the number of DCX-positive cells was relatively lower in the acute irradiation group than the fractional irradiation groups (approximately 3.6-fold), suggesting the biological change on hippocampal neurogenesis was more susceptible to being damaged by acute than fractional irradiation. These results suggest that the exposure to γ-irradiation as a long-term effect can trigger biological responses resulting in the inhibition of hippocampal neurogenesis.

  18. Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics.

    PubMed Central

    Harris, A; Joos, K; Kay, M; Evans, D; Shetty, R; Sponsel, W E; Martin, B

    1996-01-01

    AIMS/BACKGROUND: Mechanical and vascular factors may both contribute to glaucoma. This study investigated the relation of mechanical to vascular factors by examining how acute IOP elevation altered flow velocities in the central retinal and ophthalmic arteries. METHODS: IOP was elevated from a baseline near 14 to approximately 45 mm Hg using suction ophthalmodynamometry. During recovery from scleral suction, IOP fell to near 8 mm Hg. At each IOP, peak systolic and end diastolic velocities (PSV and EDV) were measured in the central retinal and ophthalmic arteries using colour Doppler imaging (Siemens Quantum 2000). Eleven healthy people served as subjects. RESULTS: Acute elevation in IOP had no effect upon PSV, EDV, or the derived resistance index in the ophthalmic artery: flow velocities in this vessel were identical at IOP of 8 mm Hg or 45 mm Hg. In contrast, in the central retinal artery, PSV and EDV fell, and the resistance index rose, in steady progression as IOP was acutely elevated (each p < 0.01). At IOP of 45 mm Hg, EDV was virtually absent and the resistance index was very nearly 1.0. CONCLUSION: Ophthalmic arterial haemodynamics are unrelated to acute fluctuations of the IOP over a wide range, suggesting that ocular hypertension itself cannot induce vascular dysfunction in this artery. In contrast, flow velocities in the central retinal artery were highly IOP dependent, implying that haemodynamic and mechanical factors are closely linked in this vascular bed. PMID:9059269

  19. Acute effects of cannabis on breath-holding duration.

    PubMed

    Farris, Samantha G; Metrik, Jane

    2016-08-01

    Distress intolerance (an individual's perceived or actual inability to tolerate distressing psychological or physiological states) is associated with cannabis use. It is unknown whether a biobehavioral index of distress intolerance, breath-holding duration, is acutely influenced (increased or decreased) by cannabis. Such information may further inform understanding of the expression of psychological or physiological distress postcannabis use. This within-subjects study examined whether smoked marijuana with 2.7%-3.0% delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed duration of breath holding. Participants (n = 88; 65.9% male) were nontreatment-seeking frequent cannabis users who smoked placebo or active THC cigarette on two separate study days and completed a breath-holding task postsmoking. Controlling for baseline breath-holding duration and participant sex, THC produced significantly shorter breath-holding durations relative to placebo. There was a significant interaction of drug administration × frequency of cannabis use, such that THC decreased breath-holding time among less frequent but not among more frequent users. Findings indicate that cannabis may exacerbate distress intolerance (via shorter breath-holding durations). As compared to less frequent cannabis users, frequent users display tolerance to cannabis' acute effects including increased ability to tolerate respiratory distress when holding breath. Objective measures of distress intolerance are sensitive to contextual factors such as acute drug intoxication, and may inform the link between cannabis use and the expression of psychological distress. (PsycINFO Database Record PMID:27454678

  20. Formaldehyde exposure and acute health effects study

    SciTech Connect

    Quackenboss, J.J.; Lebowitz, M.D.; Michaud, J.P.; Bronnimann, D. )

    1989-01-01

    To assess the effects of formaldehyde exposures on health, exposure groups were defined using baseline exposure and health questionnaires. Formaldehyde concentrations were poorly correlated with these exposure classifications, perhaps due to the time delay between classification and monitoring. The 151 households reported here had a mean HCHO concentration of 35 (S.E. 1.5 and median 30) {mu}g/m{sup 3}. Passive samplers prepared in our lab were calibrated in a chamber to derive an estimated sampling rate of 0.311 {mu}g/(mg {center dot} m{sup {minus}3} {center dot} hr). They were also compared to commercially available samplers inside of the homes, with a correlation coefficient of 0.896 and mean difference of 2.6 {mu}g/m{sup 3}. In this report of initial findings from an ongoing study, daily symptoms and peak expiratory flow measurements were compared with an HCHO exposure classification based on the median measured concentrations. None of the symptoms groups were related to HCHO exposure when controlling for age and sex. There was a significant relationship between HCHO exposure and variability in peak expiratory flows that was dependent on age group. It may be especially important to assess the variability in reactive individuals and children to determine the short-term effects of HCHO exposures and possible long-term consequences.

  1. Acute effects of aerobic exercise promote learning

    PubMed Central

    Perini, Renza; Bortoletto, Marta; Capogrosso, Michela; Fertonani, Anna; Miniussi, Carlo

    2016-01-01

    The benefits that physical exercise confers on cardiovascular health are well known, whereas the notion that physical exercise can also improve cognitive performance has only recently begun to be explored and has thus far yielded only controversial results. In the present study, we used a sample of young male subjects to test the effects that a single bout of aerobic exercise has on learning. Two tasks were run: the first was an orientation discrimination task involving the primary visual cortex, and the second was a simple thumb abduction motor task that relies on the primary motor cortex. Forty-four and forty volunteers participated in the first and second experiments, respectively. We found that a single bout of aerobic exercise can significantly facilitate learning mechanisms within visual and motor domains and that these positive effects can persist for at least 30 minutes following exercise. This finding suggests that physical activity, at least of moderate intensity, might promote brain plasticity. By combining physical activity–induced plasticity with specific cognitive training–induced plasticity, we favour a gradual up-regulation of a functional network due to a steady increase in synaptic strength, promoting associative Hebbian-like plasticity. PMID:27146330

  2. Veterinary Forensic Toxicology.

    PubMed

    Gwaltney-Brant, S M

    2016-09-01

    Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. PMID:27090769

  3. Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

    PubMed Central

    Pirela, Sandra V.; Lu, Xiaoyan; Miousse, Isabelle; Sisler, Jennifer D.; Qian, Yong; Guo, Nancy; Koturbash, Igor; Castranova, Vincent; Thomas, Treye; Godleski, John; Demokritou, Philip

    2016-01-01

    Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects. PMID:26989787

  4. The Protective Effects of Buzui on Acute Alcoholism in Mice

    PubMed Central

    Wen, Da-Chao; Gao, Shu-di; Hu, Xiao-yu; Yi, Cheng

    2016-01-01

    This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID:26884793

  5. Effects of acute exercise on long-term memory.

    PubMed

    Labban, Jeffrey D; Etnier, Jennifer L

    2011-12-01

    In this study, we tested the effect of acute exercise on long-term memory, specifically the timing of exercise relative to the memory challenge. We assessed memory via paragraph recall, in which participants listened to two paragraphs (exposure) and recounted them following a 35-min delay. Participants (n = 48) were randomly assigned to one of three groups: exercise prior to exposure, exercise after exposure, or no-exercise. Exercise consisted of 30 min on a cycle ergometer including 20 min at moderate intensity. Only the exercise prior group recalled significantly more than the control group (p < .05). Differences among the exercise groups failed to reach significance (p = .09). Results indicated that acute exercise positively influenced recall and that exercise timing relative to memory task may have an impact on this effect.

  6. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  7. Toxicology of haloacetonitriles

    SciTech Connect

    Hayes, J.R.; Condie, L.W. Jr.; Borzelleca, J.F.

    1986-11-01

    Haloacetonitriles are by-products of water chlorination and may form in vivo from the reaction of residual chlorine with endogenous compounds such as amino acids. Dibromoacetonitrile (DBAN) was negative in selected mutagenic assays; dichloroacetonitrile (DCAN) was mutagenic in S. typhimurium, but not in S. cerevisiae. Both DBAN and DCAN may be carcinogenic. The studies described were conducted to determined the acute, subacute, and subchronic toxicity of DBAN and DCAN. The acute oral LD/sub 50/ values (mg/kg) in mice and rats are: DBAN, mice: 289 (M), 303 (F); DBAN, rats: 245 (M), 361 (F); DCAN, mice: 270 (M), 279 (F); DCAN, rats: 339 (M), 330 (F). Death was preceded by slowed respiration, depressed activity, prostration, and coma. There were no apparent compound-related gross pathological effects. DBAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 23, 45, 90, and 180 mg/kg/day or 6, 23, and 45 mg/kg/day, respectively. No consistent, significant, adverse compound-related effects on any of the parameters evaluated were evident. Possible target organs might be spleen, thymus, and liver. The no-observed adverse-effect level (NOAEL) for 14 days was 45 mg/kg/day and for 90 days was 23 mg/kg/day. DCAN (in corn oil) was administered by gavage to male and female CD rats for 14 or 90 days at levels of 12, 23, 45, and 90 mg/kg/day or 8, 33, and 65 mg/kg/day, respectively. There were not deaths during the 14 day study. No consistent, significant adverse compound-related effects on any of the parameters evaluated were evident. The NOAEL for 14 days was 45 mg/kg/day and for 90 days was 9 mg/kg/day.

  8. Musk xylene: analysis, occurrence, kinetics, and toxicology.

    PubMed

    Käfferlein, H U; Göen, T; Angerer, J

    1998-09-01

    1,3-Dimethyl-2,4,6-trinitro-5-tert.-butylbenzene (musk xylene, MX), a synthetic musk, is often used in fragrances and soaps to substitute the natural musk. MX belongs to the common group of nitromusk compounds. The main environmental intake of MX occurs after sewage introduction. The consumption of fish and drinking water as well as the use of body care and perfumed household products could lead to an ingestion of this substance in humans. Although the acute oral and dermal toxicity of MX is low, some hint for the carcinogenic potential of MX was found in one animal experiment. These findings and the high potential of MX as environmental contaminant, it is stable against biological and chemical degradation and it is highly lipophil, raised considerable attention in the field of environmental medicine. Biological monitoring and the toxicology of MX, which previously has been described to occur in human milk, human fat tissue, as well as human blood samples, are of central interest. The aim of this article is to summarize the data on the analysis, occurrence, kinetics, and toxicology of MX. As there is a lack of knowledge on human toxicity and human carcinogenicity of MX, a final evaluation of the toxicological data with regard to public health is still impossible. Nevertheless, in view of the published data about MX, there is no evidence for any substantial human risk at the moment.

  9. Computational toxicology at the European Commission's Joint Research Centre.

    PubMed

    Mostrag-Szlichtyng, Aleksandra; Zaldívar Comenges, José-Manuel; Worth, Andrew P

    2010-07-01

    The methods and tools of computational toxicology form an essential and integrating pillar in the new paradigm of predictive toxicology, which seeks to develop more efficient and effective means of assessing chemical toxicity, while also reducing animal testing. The increasingly prominent role of computational toxicology in the implementation of European chemicals' legislation is described, along with initiatives by the European Commission's Joint Research Centre to promote the acceptance and use of computational methods. Outstanding needs and scientific challenges are also outlined. In recent years, there have been impressive scientific and technological advances in computational toxicology. However, considerable progress is still needed to increase the acceptance of computational methods, and in particular to develop a deeper and common understanding of how to apply computational toxicology in regulatory decision making.

  10. Toxicological Assessment of Noxious Inhalants

    PubMed Central

    Kleinsasser, N. H.; Sassen, A. W.; Wallner, B. W.; Staudenmaier, R.; Harréus, U. A.; Richter, E.

    2004-01-01

    In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects. The following essay describes the main features of toxicological assessment of inhalative environmental and workplace xenobiotics. The essay also explains relevant characteristics and limit values of noxious compounds and gases and depicts modern testing methods. To this end, emphasis is given on methods characterizing the different stages of tumorigenic processes. Various test systems have been developed which can be used in vivo, ex vivo or in vitro. They are to a great part based on the evidence of changes in DNA or particular genes of cells. Among others they have highlighted the impact of interindividual variability on enzymatic activation of xenobiotics and on susceptibility of the host to tumor diseases. Unfortunately, for many inhalative environmental noxious agents no sufficient risk profiles have been developed. The completion of these profiles should be the goal of toxicological assessment in order to allow reasonable socioeconomic or individual-based risk reduction. PMID:22073045

  11. Toxicological benchmarks for screening contaminants of potential concern for effects on sediment-associated biota: 1996 revision

    SciTech Connect

    Jones, D.S.; Suter, G.W. II; Hull, R.N.

    1996-06-01

    A hazardous waste site may contain hundred of chemicals; therefore, it is important to screen contaminants of potential concern of the ecological risk assessment. Often this screening is done as part of a Screening Assessment, the purpose of which is to evaluate the available data, identify data gaps, and screen contaminants of potential concern. |Screening may be accomplished by using a set of toxicological benchmarks. These benchmarks are helpful in determining whether contaminants warrant further assessment or are at a level that requires no further attention. If a chemical concentration or the reported detection limit exceeds a proposed lower benchmark, more analysis is needed to determine the hazards posed by that chemical. If, however, the chemical concentration falls below the lower benchmark value, the chemical may be eliminated from further study. This report briefly describes three categories of approaches to the development of sediment quality benchmarks. These approaches are based on analytical chemistry, toxicity test results, and field survey data. A fourth integrative approach incorporates all three types of data.

  12. REINFORCEMENT ENHANCING EFFECTS OF ACUTE NICOTINE VIA ELECTRONIC CIGARETTES

    PubMed Central

    Perkins, Kenneth A.; Karelitz, Joshua L.; Michael, Valerie C.

    2015-01-01

    Background Recent human studies confirm animal research showing that nicotine enhances reinforcement from rewards unrelated to nicotine. These effects of acute nicotine via tobacco smoking may also occur when consumed from non-tobacco products. Methods We assessed acute effects of nicotine via electronic cigarettes (“e-cigarettes”) on responding reinforced by music, video, or monetary rewards, or for no reward (control). In a fully within-subjects design, adult dependent smokers (N=28) participated in three similar experimental sessions, each following overnight abstinence (verified by CO≤10 ppm). Varying only in e-cigarette condition, sessions involved controlled exposure to a nicotine (labeled “36 mg/ml”) or placebo (“0”) e-cigarette, or no e-cigarette use. A fourth session involved smoking one’s own tobacco cigarette brand after no abstinence, specifically to compare responses under typical nicotine satiation with these acute e-cigarette conditions after abstinence. Results Reinforced responding for video reward, but not the other rewards, was greater due to use of the nicotine versus placebo e-cigarette (i.e., nicotine per se), while no differences were found between the placebo e-cigarette and no e-cigarette conditions (i.e., e-cigarette use per se). For nicotine via tobacco smoking, responding compared to the nicotine e-cigarette was similar for video but greater for music, while both video and music reward were enhanced relative to the non-nicotine conditions (placebo and no e-cigarette). Conclusions Acute nicotine from a non-tobacco product has some reinforcement enhancing effects in humans, in a manner partly consistent with nicotine via tobacco smoking and perhaps contributing to the rising popularity of nicotine e-cigarette use. PMID:26070455

  13. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    PubMed Central

    Islambulchilar, Mina; Asvadi, Iraj; Sanaat, Zohreh; Esfahani, Ali; Sattari, Mohammadreza

    2015-01-01

    Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally). Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that the levels of white blood cells are significantly (P<0.05) increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05) lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes. PMID:25789226

  14. Historical perspectives on cadmium toxicology

    SciTech Connect

    Nordberg, Gunnar F.

    2009-08-01

    The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects were studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.

  15. Aquatic toxicology: fact or fiction?

    PubMed Central

    Macek, K J

    1980-01-01

    A brief history of the development of the field of aquatic toxicology is provided. In order to provide a perspective on the state-of-the-art in aquatic toxicology relative to classical toxicology, the two fields are compared from the standpoint of the type of scientist practicing each field, the respective objectives of each, the forces which drive the activity in each field, and the major advantages and disadvantages accruing to the practitioner of aquatic toxicology as a result of the differences in objectives and driving forces. PMID:6993200

  16. Translational toxicology: a developmental focus for integrated research strategies

    PubMed Central

    2013-01-01

    Background Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Discussion Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures. The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan 2) Defining modes of action and relevance of data from animal models 3) Use of mathematical models to develop plausible predictions as the basis for 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Summary Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics. PMID:24079609

  17. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  18. Toxicological benchmarks for screening contaminants of potential concern for effects on sediment-associated biota: 1994 Revision. Environmental Restoration Program

    SciTech Connect

    Hull, R.N. |; Suter, G.W. II

    1994-06-01

    Because a hazardous waste site may contain hundreds of chemicals, it is important to screen contaminants of potential concern for the ecological risk assessment. Often this screening is done as part of a Screening Assessment, the purpose of which is to evaluate the available data, identify data gaps, and screen contaminants of potential concern. Screening may be accomplished by using a set of toxicological benchmarks. These benchmarks are helpful in determining whether contaminants warrant further assessment or are at a level that requires no further attention. If a chemical concentration or the reported detection limit exceeds a proposed lower benchmark, more analysis is needed to determine the hazards posed by that chemical. If, however, the chemical concentration falls below the lower benchmark value, the chemical may be eliminated from further study. This report briefly describes three categories of approaches to the development of sediment quality benchmarks. These approaches are based on analytical chemistry, toxicity test and field survey data. A fourth integrative approach incorporates all three types of data. The equilibrium partitioning approach is recommended for screening nonpolar organic contaminants of concern in sediments. For inorganics, the National Oceanic and Atmospheric Administration has developed benchmarks that may be used for screening. There are supplemental benchmarks from the province of Ontario, the state of Wisconsin, and US Environmental Protection Agency Region V. Pore water analysis is recommended for polar organic compounds; comparisons are then made against water quality benchmarks. This report is an update of a prior report. It contains revised ER-L and ER-M values, the five EPA proposed sediment quality criteria, and benchmarks calculated for several nonionic organic chemicals using equilibrium partitioning.

  19. Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

    NASA Technical Reports Server (NTRS)

    Scully, R. R.; Alexander, D. J.; Ryder, V. E.; Lam, C. W.; Statish, U.; Basner, M.

    2016-01-01

    controlled at levels that are well below current spacecraft limits. Our study will extend the earlier study to determine if crew-like subjects are similarly effected by CO2. In addition to employing the Strategic Management Simulation tool, we will use the Cognition battery of psychometric measures that are being utilized aboard the ISS. It will be important to learn, by using Cognition, if additional cognitive domains are sensitive to concentrations of CO2 at or below limits currently controlled by flight rules. While spaceflight Cognition data will greatly enhance the knowledge base related to inflight behavioral health and performance, some of the measures may be influenced by fatigue (related to sleep deprivation and or workload) and changes in circadian rhythms. Therefore our use of this battery of tests in a well-controlled, ground-based study that is free of these potential confounding influences will establish a baseline terrestrial data set against which Cognition data collected in flight may be assessed. The findings from this study will be useful to the NASA Toxicology Office and the National Research Council Committee on Toxicology, which assists NASA in setting environmental standards, for revision of the SMAC for CO2, and for designing further studies on effects of CO2 upon cognitive functions.

  20. Synthetic toxicology: where engineering meets biology and toxicology.

    PubMed

    Schmidt, Markus; Pei, Lei

    2011-03-01

    This article examines the implications of synthetic biology (SB) for toxicological sciences. Starting with a working definition of SB, we describe its current subfields, namely, DNA synthesis, the engineering of DNA-based biological circuits, minimal genome research, attempts to construct protocells and synthetic cells, and efforts to diversify the biochemistry of life through xenobiology. Based on the most important techniques, tools, and expected applications in SB, we describe the ramifications of SB for toxicology under the label of synthetic toxicology. We differentiate between cases where SB offers opportunities for toxicology and where SB poses challenges for toxicology. Among the opportunities, we identified the assistance of SB to construct novel toxicity testing platforms, define new toxicity-pathway assays, explore the potential of SB to improve in vivo biotransformation of toxins, present novel biosensors developed by SB for environmental toxicology, discuss cell-free protein synthesis of toxins, reflect on the contribution to toxic use reduction, and the democratization of toxicology through do-it-yourself biology. Among the identified challenges for toxicology, we identify synthetic toxins and novel xenobiotics, biosecurity and dual-use considerations, the potential bridging of toxic substances and infectious agents, and do-it-yourself toxin production. PMID:21068213

  1. Acute effects of ethanol on renal folate clearance in rats

    SciTech Connect

    Eisenga, B.H.; McMartin, K.E.

    1986-03-05

    Studies of the renal clearance of folic acid in primates demonstrate net reabsorption of folate by a saturable system. The acute administration of ethanol to rats causes a significant increase in urinary folate excretion. The mechanism for this effect is unknown and thus the effect of acute administration of ethanol on the renal absorption and urinary clearance of folate was studied in rats. Folic acid was administered to male Sprague-Dawley rats via continuous intravenous infusion in doses ranging from 3-75 micromoles/kg and renal clearance relative to inulin was determined. The effects of various dose levels of ethanol on these parameters were then determined. At a dose of 15 micromoles/kg, the renal clearance of folate relative to that of inulin was about 0.65 mg/min. At a plasma ethanol level about 100 mg/dl, the renal clearance of folate was not markedly altered. These results suggests that there is net reabsorption of folate in the rat kidney and that moderate doses of ethanol have little effect on renal effect on renal folate reabsorption.

  2. Effects of acute exposure to aluminum on cognition in humans.

    PubMed

    Molloy, D W; Standish, T I; Nieboer, E; Turnbull, J D; Smith, S D; Dubois, S

    2007-12-01

    There is epidemiological evidence suggesting an association between aluminum in drinking water and Alzheimer's disease (AD), and between aluminum in dialysate and dialysis dementia. The exact role of aluminum in the pathogenesis of these and other dementias is not clear. This study examined the acute effects of aluminum on cognitive function in patients with AD and related dementias and in age-matched and younger volunteers with normal cognitive function. Whether individuals with AD and/or the APOE epsilon4 genotype had enhanced gastrointestinal absorption of aluminum was tested, and whether individuals with elevated blood aluminum concentrations exhibited acute cognitive effects was determined. Subjects were randomized to receive a single dose of aluminum orally (Amphojel plus citrate) for 3 d followed by a 3-wk washout, and then 3 d of matched placebo administration, or vice versa. Serum aluminum levels were measured and the daily dose of Amphojel was adjusted to a target aluminum level between 50 and 150 microg/L. Neuropsychological tests were administered at baseline and 90 min after the third dose of Amphojel or placebo. There was a large interindividual variation in aluminum serum levels in all study groups after the same initial dose of Amphojel. There were no significant differences in neuropsychological test scores after aluminum ingestion in normal volunteers or in patients with cognitive impairment. There was no association between APOE epsilon4 genotype and aluminum absorption. The results did not support the hypothesis that aluminum ingested at these doses produces acute effects on cognition or adverse effects, nor did they reveal that AD patients are more vulnerable to such outcomes. Further inquiry is required to explore any possible association between aluminum and cognition, but controlled trials may be limited by safety concerns.

  3. [Research advances in eco-toxicological diagnosis of soil pollution].

    PubMed

    Liu, Feng; Teng, Hong-Hui; Ren, Bai-Xiang; Shi, Shu-Yun

    2014-09-01

    Soil eco-toxicology provides a theoretical basis for ecological risk assessment of contaminated soils and soil pollution control. Research on eco-toxicological effects and molecular mechanisms of toxic substances in soil environment is the central content of the soil eco-toxicology. Eco-toxicological diagnosis not only gathers all the information of soil pollution, but also provides the overall toxic effects of soil. Therefore, research on the eco-toxicological diagnosis of soil pollution has important theoretical and practical significance. Based on the research of eco-toxicological diagnosis of soil pollution, this paper introduced some common toxicological methods and indicators, with the advantages and disadvantages of various methods discussed. However, conventional biomarkers can only indicate the class of stress, but fail to explain the molecular mechanism of damage or response happened. Biomarkers and molecular diagnostic techniques, which are used to evaluate toxicity of contaminated soil, can explore deeply detoxification mechanisms of organisms under exogenous stress. In this paper, these biomarkers and techniques were introduced systematically, and the future research trends were prospected.

  4. Reprint Library for Toxicology Data Bank

    ERIC Educational Resources Information Center

    Agarwal, S. N.; Khan, R. R.

    1975-01-01

    The Industrial Toxicology Research Center, Lucknow, India, maintains a register of toxicology and provides its research workers with current information mainly through its collection of reprints. (Author)

  5. Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos

    EPA Science Inventory

    Summary sentence: Comparative toxicology of Libby amphibole (LA) and site-specific naturally occurring asbestos (NOA) provides new insights on physical properties influencing health effects and mechanisms of asbestos-induced inflammation, fibrosis, and tumorigenesis.Introduction/...

  6. 75 FR 52535 - Availability of Draft Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ..., ATSDR, in cooperation with the National Toxicology Program (NTP), may plan a program of research designed to determine these health effects. Although a number of key studies for this substance...

  7. Defining the Toxicology of Aging

    PubMed Central

    Sorrentino, Jessica A.; Sanoff, Hanna K.; Sharpless, Norman E.

    2014-01-01

    Mammalian aging is complex and incompletely understood. While significant effort has been spent addressing the genetics or, more recently, the pharmacology of aging, the toxicology of aging has been relatively understudied. Just as an understanding of `carcinogens' has proven critical to modern cancer biology, an understanding of environmental toxicants that accelerate aging (`gerontogens') will inform gerontology. In this review, we discuss the evidence for the existence of mammalian gerontogens, as well as describe biomarkers needed to measure the age-promoting activity of a given toxicant. We focus on the effects of putative gerontogens on the in vivo accumulation of senescent cells, a characteristic feature of aging that plays a causal role in some age-associated phenotypes. PMID:24880613

  8. The toxicology of inhaled woodsmoke.

    PubMed

    Zelikoff, Judith T; Chen, Lung Chi; Cohen, Mitchell D; Schlesinger, Richard B

    2002-01-01

    In addition to developing nations relying almost exclusively upon biomass fuels, such as wood for cooking and home heating, North Americans, particularly in Canada and the northwestern and northeastern sections of the United States, have increasingly turned to woodburning as an alternate method for domestic heating because of increasing energy costs. As a result, the number of households using woodburning devices has increased dramatically. This has resulted in an increase in public exposure to indoor and outdoor woodsmoke-associated pollutants, which has prompted widespread concern about the adverse human health consequences that may be associated with prolonged woodsmoke exposure. This mini-review article brings together many of the human and animal studies performed over the last three decades in an attempt to better define the toxicological impact of inhaled woodsmoke on exposed children and adults; particular attention is given to effects upon the immune system. General information regarding occurrence and woodsmoke chemistry is provided so as to set the stage for a better understanding of the toxicological impact. It can be concluded from this review that exposure to woodsmoke, particularly for children, represents a potential health hazard. However, despite its widespread occurrence and apparent human health risks, relatively few studies have focused upon this particular area of research. More laboratory studies aimed at understanding the effects and underlying mechanisms of woodsmoke exposure, particularly on those individuals deemed to be at greatest risk, are badly needed, so that precise human health risks can be defined, appropriate regulatory standards can be set, and accurate decisions can be made concerning the use of current and new woodburning devices.

  9. Toxicological evaluation of u-hEGF.

    PubMed

    Maraschin, R; Bussi, R; Conz, A; Orlando, L; Pirovano, R; Nyska, A

    1995-01-01

    The toxicological evaluation of urinary human epidermal growth factor (u-hEGF) included mutagenicity, single and repeated dose general toxicity, and teratogenicity studies in various animal species. The mutagenic potential of u-hEGF was tested in vitro (Ames test, chromosome aberration in human lymphocytes, unscheduled DNA synthesis in HeLa cells) and in vivo (chromosome aberration in Chinese hamster bone marrow and micronucleus test in rat bone marrow). No mutagenic or clastogenic effects were found. The acute toxicity of u-hEGF was evaluated in mice and rats, using single subcutaneous (sc) or intravenous (i.v.) injection of 15 mg/kg. No toxic effects were observed Four-week i.v. daily administration of u-hEGF at the doses of 0.3, o.9, and 3 mg/kg in the SD rat followed by 2 wk of compound withdrawal induced pronounced and generally dose-related effects (i.e., epithelial hyperplasia) in a wide range of tissues and organs, at all doses. However, these effects were not apparently detrimental to the general health of the rats. The repeated sc administration of u-hEGF to cynomolgus monkeys for 4 wk at the same doses as used in the rat study resulted in lethality after about 7 days of treatment in the 2 higher dose groups or after 14 days at the lowest dose. The main clinical signs observed were gastrointestinal effects, respiratory distress, sedation, marked loss of body weight, and cutaneous desquamation. At histology, hyperplasia of most epithelia was seen in all groups. In addition, atrophy of the ovarian follicles and necrosis of the uterine endometrium were noted. Changes considered secondary to physical distress were atrophy of the hemopoietic and lymphatic system and hepatic steatosis. The embryofetal toxicity and teratogenicity of u-hEGF was tested, using the i.v. route in the SD rat and the i.v. and sc routes in the New Zealand White rabbit. In both species, the compound was administered at the doses of 0, 0.3, 0.9, and 3 mg/kg/day, from day 6 to 15 of

  10. Acute effects of routine firefighting on lung function.

    PubMed

    Sheppard, D; Distefano, S; Morse, L; Becker, C

    1986-01-01

    We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The effects of acute nicotine on contextual safety discrimination.

    PubMed

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients.

  12. The effects of acute nicotine on contextual safety discrimination.

    PubMed

    Kutlu, Munir G; Oliver, Chicora; Gould, Thomas J

    2014-11-01

    Anxiety disorders, such as post-traumatic stress disorder (PTSD), may be related to an inability to distinguish safe versus threatening environments and to extinguish fear memories. Given the high rate of cigarette smoking in patients with PTSD, as well as the recent finding that an acute dose of nicotine impairs extinction of contextual fear memory, we conducted a series of experiments to investigate the effect of acute nicotine in an animal model of contextual safety discrimination. Following saline or nicotine (at 0.0275, 0.045, 0.09 and 0.18 mg/kg) administration, C57BL/6J mice were trained in a contextual discrimination paradigm, in which the subjects received presentations of conditioned stimuli (CS) that co-terminated with a foot-shock in one context (context A (CXA)) and only CS presentations without foot-shock in a different context (context B (CXB)). Therefore, CXA was designated as the 'dangerous context', whereas CXB was designated as the 'safe context'. Our results suggested that saline-treated animals showed a strong discrimination between dangerous and safe contexts, while acute nicotine dose-dependently impaired contextual safety discrimination (Experiment 1). Furthermore, our results demonstrate that nicotine-induced impairment of contextual safety discrimination learning was not a result of increased generalized freezing (Experiment 2) or contingent on the common CS presentations in both contexts (Experiment 3). Finally, our results show that increasing the temporal gap between CXA and CXB during training abolished the impairing effects of nicotine (Experiment 4). The findings of this study may help link nicotine exposure to the safety learning deficits seen in anxiety disorder and PTSD patients. PMID:25271215

  13. The effect of benzo(a)pyrene on porcine urinary bladder epithelial cells analyzed for the expression of selected genes and cellular toxicological endpoints.

    PubMed

    Wolf, Alexander; Kutz, Alexandra; Plöttner, Sabine; Behm, Claudia; Bolt, Herrmann M; Föllmann, Wolfram; Kuhlmann, Jürgen

    2005-02-14

    Consumption of tobacco products is the most relevant risk factor for the development of bladder cancer beside occupational contributions. In order to investigate mechanisms of tobacco smoke components in bladder carcinogenesis we have introduced a primary epithelial cell culture system derived from porcine urinary bladder as a suitable representative for the corresponding human tissue under physiological conditions. Two independent readouts were selected as markers for genotoxic events. Changes in the expression level of several toxicologically relevant genes should serve as indicators for early response, while classical genotoxic endpoints monitored manifested damages. Here, we present the first results of our study with benzo(a)pyrene (BaP) as a member of polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. Cells treated with BaP show a dramatic increase in the expression of CYP1A1 that appears to be both indicator of and contributor for BaP toxicity. Genes coding for other proteins relevant in xenobiotic metabolism, signal transduction or tumor suppression show moderate effects or no enhancement of their expression levels. Comet assay and micronucleus test did show a significant, dose-dependent increase in DNA damages or aberrations after cell division. While these effects are conforming to the response at the mRNA expression level, they are less pronounced and require rather higher dosages of the chemical.

  14. Toxicological effects of a mixture used in weight loss products: p-synephrine associated with ephedrine, salicin, and caffeine.

    PubMed

    Schmitt, Gabriela C; Arbo, Marcelo D; Lorensi, Andréia L; Maciel, Erica S; Krahn, Carolina L; Mariotti, Kristiane C; Dallegrave, Eliane; Leal, Mirna B; Limberger, Renata P

    2012-03-01

    p-Synephrine is an adrenergic amine found in Citrus aurantium L. fruits and has been used for weight loss in dietary supplements. There are commercial products containing this substance associated to caffeine, salicin, and ephedrine. The aim of this study was to evaluate the acute toxicity of this mixture in mice of both sexes. The significative results observed after acute oral administration to male and female mice of 300, 350, and 400 mg/kg total of p-synephrine, ephedrine, salicin, plus caffeine in a 10:4:6:80 w/w ratio included a reduction in locomotor activity and ptosis in all treated groups for both sexes. Seizures were also observed in male (400 mg/kg) and female groups (350 and 400 mg/kg). Gasping and tearing were observed in males. Salivation (400 mg/kg), agitation (350 and 400 mg/kg), and piloerection (all treated groups) were significantly observed only in females. Deaths occurred in males at 350 and 400 mg/kg treated groups and the necropsy showed cardiopulmonary hemorrhage. A reduction in locomotor activity was confirmed through the spontaneous locomotor activity test, in which the number of crossings considerably decreased (P < .01) in all treated groups. The rotarod test showed a decrease in motor coordination at 400 mg/kg. Body temperature decreased significantly (P < .01) in all treated groups compared to controls. The results suggested clear signs of toxicity of p-synephrine, ephedrine, salicin, and caffeine association; this toxicity augments the attentiveness on commercial products containing this mixture, given the expressive number of adverse events related to its utilization.

  15. [Toxicology screening in paediatrics].

    PubMed

    Garcia-Algar, Óscar; Cuadrado González, Ainoha; Falcon, María

    2016-09-01

    The prevalence of acute or chronic exposure to substances of abuse in paediatric patients, from the neonatal period to adolescence, is not well established as most cases go unnoticed. Regardless of clinical cases of acute poisoning leading to visits to emergency room, the exposure is usually detected by a questionnaire to the parents or children. In the last few years, new validated analytical methodologies have been developed in order to detect parent drugs and their metabolites in different biological matrices. These biological matrices have different time windows for detection of the exposure: acute (i.e., urine, blood, oral fluid), and chronic (i.e., hair, meconium or teeth). The aim of this paper was to review the scenarios where the use of biological matrices is indicated for the detection of acute or chronic exposure to substances of abuse. PMID:26458521

  16. [Toxicology screening in paediatrics].

    PubMed

    Garcia-Algar, Óscar; Cuadrado González, Ainoha; Falcon, María

    2016-09-01

    The prevalence of acute or chronic exposure to substances of abuse in paediatric patients, from the neonatal period to adolescence, is not well established as most cases go unnoticed. Regardless of clinical cases of acute poisoning leading to visits to emergency room, the exposure is usually detected by a questionnaire to the parents or children. In the last few years, new validated analytical methodologies have been developed in order to detect parent drugs and their metabolites in different biological matrices. These biological matrices have different time windows for detection of the exposure: acute (i.e., urine, blood, oral fluid), and chronic (i.e., hair, meconium or teeth). The aim of this paper was to review the scenarios where the use of biological matrices is indicated for the detection of acute or chronic exposure to substances of abuse.

  17. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

    PubMed

    Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools. PMID:27119030

  18. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    PubMed Central

    Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools. PMID:27119030

  19. Effectiveness of chelation therapy with time after acute uranium intoxication

    SciTech Connect

    Domingo, J.L.; Ortega, A.; Llobet, J.M.; Corbella, J. )

    1990-01-01

    The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

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

    PubMed

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

    2010-10-01

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

  1. Acute effects of carbon monoxide on cardiac electrical stability

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A. )

    1990-10-01

    The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state.

  2. Toxicological evaluation of myristicin.

    PubMed

    Hallström, H; Thuvander, A

    1997-01-01

    Myristicin, or methoxysafrole, is the principal aromatic constituent of the volatile oil of nutmeg, the dried ripe seed of Myristica fragrans. Myristicin is also found in several members of the carrot family (Umbelliferae). Several intoxications have been reported after an ingestion of approximately 5 g of nutmeg, corresponding to 1-2 mg myristicin/kg body weight (b.w.). Although these intoxications may be ascribed to the actions of myristicin, it is likely that other components of nutmeg may also be involved. The metabolism of myristicin resembles that of safrole. No information is available, however, concerning the quantitative importance of the different metabolic pathways. The acute toxicity of myristicin appears to be low. No toxic effects were observed in rats administered myristicin perorally at a dose of 10 mg/kg b.w., while 6-7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. A weak DNA-binding capacity has been demonstrated, but there are no indications that myristicin exerts carcinogenic activity in short-term assays using mice. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated to a few mg per person and day in this report, would cause adverse effects in humans. It is, however, at present not possible to make a complete risk assessment, as studies regarding genotoxicity and chronic toxicity, including reproductive toxicity and carcinogenicity, are still lacking. PMID:9496377

  3. Toxicology of chemical mixtures: experimental approaches, underlying concepts, and some results.

    PubMed

    Yang, R S; Hong, H L; Boorman, G A

    1989-12-01

    The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, there is yet no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the city of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last 2 years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology. PMID:2690403

  4. Toxicology of chemical mixtures: Experimental approaches, underlying concepts, and some results

    SciTech Connect

    Yang, R.S.; Long, H.L.; Boorman, G.A.

    1990-07-01

    The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, as yet there is no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the city of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last two years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology.

  5. Honey bee toxicology.

    PubMed

    Johnson, Reed M

    2015-01-01

    Insecticides are chemicals used to kill insects, so it is unsurprising that many insecticides have the potential to harm honey bees (Apis mellifera). However, bees are exposed to a great variety of other potentially toxic chemicals, including flavonoids and alkaloids that are produced by plants; mycotoxins produced by fungi; antimicrobials and acaricides that are introduced by beekeepers; and fungicides, herbicides, and other environmental contaminants. Although often regarded as uniquely sensitive to toxic compounds, honey bees are adapted to tolerate and even thrive in the presence of toxic compounds that occur naturally in their environment. The harm caused by exposure to a particular concentration of a toxic compound may depend on the level of simultaneous exposure to other compounds, pathogen levels, nutritional status, and a host of other factors. This review takes a holistic view of bee toxicology by taking into account the spectrum of xenobiotics to which bees are exposed. PMID:25341092

  6. Honey bee toxicology.

    PubMed

    Johnson, Reed M

    2015-01-01

    Insecticides are chemicals used to kill insects, so it is unsurprising that many insecticides have the potential to harm honey bees (Apis mellifera). However, bees are exposed to a great variety of other potentially toxic chemicals, including flavonoids and alkaloids that are produced by plants; mycotoxins produced by fungi; antimicrobials and acaricides that are introduced by beekeepers; and fungicides, herbicides, and other environmental contaminants. Although often regarded as uniquely sensitive to toxic compounds, honey bees are adapted to tolerate and even thrive in the presence of toxic compounds that occur naturally in their environment. The harm caused by exposure to a particular concentration of a toxic compound may depend on the level of simultaneous exposure to other compounds, pathogen levels, nutritional status, and a host of other factors. This review takes a holistic view of bee toxicology by taking into account the spectrum of xenobiotics to which bees are exposed.

  7. Diagnostic and forensic toxicology.

    PubMed

    Galey, F D

    1995-12-01

    In most competent veterinary diagnostic laboratories, analytical findings are interpreted by the veterinary toxicologist to determine the significance of the finding in view of historic, clinical, and pathologic findings. A veterinary toxicologist also will provide consultation about possible toxic rule-outs for a case, treatment of affected animals, and prevention of additional cases. Once all of the information is available, a complete summary of the findings can be provided to the client. When the procedures outlined are followed, including a systematic approach to collecting all the evidence (historic, clinical, pathologic, and analytic), proper sampling techniques, and good communication between the clinician and the client and laboratory, the usefulness of the toxicology investigation will be maximized.

  8. Overview of inhalation toxicology.

    PubMed Central

    Dorato, M A

    1990-01-01

    The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres of a wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals. Images FIGURE 1. FIGURE 3. FIGURE 7. FIGURE 8. PMID:2200660

  9. Toxicology in business decision making.

    PubMed

    Deisler, P F

    1982-12-01

    More than ever before, toxicology and its sister health sciences and technologies are needed as members of the business team to ensure sound business decision making for both new and existing businesses. Yet the marriage of toxicology and business is an uneasy one since toxicology is both the bringer of bad news and a major resource for the solution of problems. Both business and toxicology have much to learn about each other to make the marriage work and to make full use of toxicology's scientific advice in reaching sound decisions on the safe production, distribution, and handling of a company's products. Toxicology also has a central and difficult role in helping business navigate the turbulent waters of regulation or of potential or actual litigation. From his own experience in organizing a corporate health, safety, and environmental department, the author describes the concepts that must be understood and the marshaling of resources needed to ensure that toxicology can play its full role in business decision making.

  10. Seasonal pattern of the acute mortality effects of air pollution.

    PubMed

    Qian, Zhengmin; Lin, Hung-Mo; Stewart, Walter F; Kong, Linli; Xu, Fen; Zhou, Denjin; Zhu, Zhicao; Liang, Shengwen; Chen, Weiqing; Shah, Nirav; Stetter, Christy; He, Qingci

    2010-04-01

    Evidence of seasonal variation of acute mortality effects of air pollution is inconsistent. The seasonal patterns of associations between daily mortality and daily mean concentrations of particulate matter 10 microm or less in aerodynamic diameter (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2) were examined using 4 yr of data (2001-2004) in Wuhan, China. Four distinct seasons occur in Wuhan, where approximately 4.5 million residents live in the city core area of 201 km2. Air pollution levels are higher and pollution ranges are wider in Wuhan than in most cities. Quasi-likelihood estimation within the context of the generalized additive models (natural spline [NS] models in R) was used to model the natural logarithm of the expected daily death counts as a function of the predictor variables. The estimates of the interaction between seasons and pollution were obtained from the main effects and pollutant season interaction models. It was found that the interactions between three pollutants and cause-specific mortality were statistically significant (P < 0.05). The strongest effects occurred consistently in winter for all-natural, cardiovascular, stroke, and respiratory mortality. Every 10-microg/m3 increase in PM10 daily concentration at lag 0-1 days was associated with an increase in all-natural mortality of 0.69% (95% confidence interval [CI]: 0.44-0.94%) for winter, 0.34% (95% CI: 0.00-0.69%) for spring, 0.45% (95% CI: -0.13 to 1.04%) for summer, and -0.21% (95% CI: -0.54 to 0.12%) for fall. The results show a clear seasonal pattern of acute mortality effects of ambient air pollution and the strongest effects occurred during winter in the study city.

  11. Gender-Specific Toxicological Effects of Chronic Exposure to Pure Microcystin-LR or Complex Microcystis aeruginosa Extracts on Adult Medaka Fish.

    PubMed

    Le Manach, Séverine; Khenfech, Nour; Huet, Hélène; Qiao, Qin; Duval, Charlotte; Marie, Arul; Bolbach, Gérard; Clodic, Gilles; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-08-01

    Cyanobacterial blooms often occur in freshwater lakes and constitute a potential health risk to human populations, as well as to other organisms. However, their overall and specific implications for the health of aquatic organisms that are chronically and environmentally exposed to cyanobacteria producing hepatotoxins, such as microcystins (MCs), together with other bioactive compounds have still not been clearly established and remain difficult to assess. The medaka fish was chosen as the experimental aquatic model for studying the cellular and molecular toxicological effects on the liver after chronic exposures (28 days) to environmentally relevant concentrations of pure MC-LR, complex extracts of MC producing or nonproducing cyanobacterial biomasses, and of a Microcystis aeruginosa natural bloom. Our results showed a higher susceptibility of females to the different treatments compared to males at both the cellular and the molecular levels. Although hepatocyte lysis increased with MC-containing treatments, lysis always appeared more severe in the liver of females compare to males, and the glycogen cellular reserves also appeared to decrease more in the liver of females compared to those in the males. Proteomic investigations reveal divergent responses between males and females exposed to all treatments, especially for proteins involved in metabolic and homeostasis processes. Our observations also highlighted the dysregulation of proteins involved in oogenesis in female livers. These results suggest that fish populations exposed to cyanobacteria blooms may potentially face several ecotoxicological issues.

  12. Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. II. Ninety-day study.

    PubMed

    Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

    2015-02-01

    Carbon monoxide (CO), carbon dioxide (CO2) and low-level oxygen (O2) (hypoxia) are submarine atmosphere components of highest concern because of a lack of toxicological data available to address the potential effects from long-duration, combined exposures on female reproductive and developmental health. In this study, subchronic toxicity of mixed atmospheres of these three submarine air components was evaluated in rats. Male and female rats were exposed via inhalation to clean air (0.4 ppm CO; 0.13% CO2; 20.6% O2) (control), a low-dose (5.0 ppm CO; 0.41% CO2; 17.1% O2), a mid-dose (13.9 ppm CO; 1.19 or 1.20% CO2; 16.1% O2) and a high-dose (89.9 ppm CO; 2.5% CO2; 15.0% O2) gas mixture for 23 h per day for 70 d premating and a 14-d mating period. Impregnated dams continued exposure to gestation day 19. Adverse reproductive effects were not identified in exposed parents (P0) or first (F1) and second generation (F2) offspring during mating, gestation or parturition. No adverse changes to the estrous cycle or in reproductive hormone concentrations were identified. The exposure-related effects were reduced weight gains and adaptive up-regulation of erythropoiesis in male rats from the high-dose group. No adverse, dose-related health effects on clinical data or physiological data were observed. Neurobehavioral tests identified no apparent developmental deficits at the tested levels of exposure. In summary, subchronic exposures to the submarine atmosphere gases did not affect the ability of the exposed rats or their offspring to reproduce and did not appear to have any significant adverse health effects.

  13. Therapeutic effect of hyperbaric oxygenation in acute acoustic trauma.

    PubMed

    Vavrina, J; Müller, W

    1995-01-01

    Retrospectively 78 patients with uni- or bilateral acute acoustic trauma (AAT) were evaluated to assess the therapeutic effect of hyperbaric oxygenation (HBO). All subjects received saline or dextran (Rheomacodrex) infusions with Ginkgo extracts (Tebonin) and prednisone. Thirty six patients underwent additional hyperbaric oxygenation at a pressure of 2 atmospheres absolute for 60 minutes once daily. Both treatment groups were comparable as far as age, gender, initial hearing loss and prednisone dose are concerned. The delay of therapy onset was 15 hours in both groups and treatment was started within 72 hours in all cases. Control audiometry was performed after 6.5 days, when the HBO group had had 5 exposures to hyperbaric oxygenation. The average hearing gain in the group without HBO was 74.3 dB and in the group treated additionally with HBO 121.3 dB (P < 0.004). It is concluded, that hyperbaric oxygenation significantly improves hearing recovery after AAT. Therefore acute acoustic trauma with significant hearing threshold depression remains an otological emergency. Minimal therapy involving waiting for spontaneous recovery, which is mostly incomplete leaving a residual C5 or C6 and handicapping tinnitus, is not the treatment of choice. Randomized prospective clinical trials with a larger patient series are needed and further experimental studies are required to understand the physiological mechanisms of HBO responsible for the clinical success in AAT.

  14. Acute and chronic respiratory effects of sodium borate particulate exposures.

    PubMed Central

    Wegman, D H; Eisen, E A; Hu, X; Woskie, S R; Smith, R G; Garabrant, D H

    1994-01-01

    This study examined work-related chronic abnormality in pulmonary function and work-related acute irritant symptoms associated with exposure to borate dust in mining and processing operations. Chronic effects were examined by pulmonary function at the beginning and end of a 7-year interval. Time-specific estimates of sodium borate particulate exposures were used to estimate cumulative exposure during the study interval. Change in pulmonary function over the 7 years was found unrelated to the estimate of cumulative exposure during that interval. Exposure-response associations also were examined with respect to short-term peak exposures and incidence of five symptoms of acute respiratory irritation. Hourly measures of health outcome and continuous measures of particulate exposure were made on each subject throughout the day. Whenever a subject reported one of the irritant symptoms, a symptom intensity score was also recorded along with the approximate time of onset. The findings indicated that exposure-response relationships were present for each of the specific symptoms at several symptom intensity levels. The associations were present when exposure was estimated by both day-long and short-term (15-min) time-weighted average exposures. Associations persisted after taking account of smoking, age, and the presence of a common cold. No significant difference in response rate was found between workers exposed to different types of sodium borate dusts. PMID:7889871

  15. The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis.

    PubMed

    Li, Renyan; Luo, Xue; Li, Lianbing; Peng, Qiang; Yang, Yuyou; Zhao, Letian; Ma, Mingfu; Hou, Zhiwei

    2016-03-01

    Cadmium (Cd) is widely used in daily life and was recently recognized as a possible source of human toxicity due to its ability to accumulate in organs. Previous studies have shown that Cd exposure may cause testicular toxicity through oxidative stress and an inflammatory effect. Melatonin has been demonstrated to be an effective anti-oxidant and has an anti-inflammatory effect. The aim of the present study was to investigate the toxicological effects of Cd on reproduction in male mice and the potential protective action of melatonin against these adverse effects. Adult male mice were injected intraperitoneally with Cd at a dose of 2 mg/kg body weight per day for seven consecutive days with or without melatonin pretreatment. Sex organ weight, sperm parameters including sperm quality, apoptosis, acrosome integrity, mitochondrial membrane potential, testicular morphology, serum sex hormone, inflammatory status, and oxidative stress were evaluated. The results showed that significant adverse effects were observed in the male reproductive system after Cd exposure, including alterations in sperm parameters, increased DNA damage, and sex hormone disturbance. Acute Cd exposure also significantly increased malondialdehyde (MDA) contents, decreased glutathione (GSH) and superoxide dismutase (SOD) activities, and upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β), in the testis. In contrast, melatonin pretreatment significantly alleviated these toxic effects, and its mechanism may involve inhibiting MDA level, restoring GSH and SOD activities, and reducing the upregulation of TNF-α and IL-1β. Our data suggest that oxidative stress and inflammation are involved in Cd-induced toxicity in the male reproductive system and that co-administration of melatonin exerts a protective effect against Cd-induced male reproductive toxicity. PMID:26224376

  16. Nano-technology and nano-toxicology

    PubMed Central

    Maynard, Robert L.

    2012-01-01

    Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology. PMID:22662021

  17. Ethical Considerations for Perinatal Toxicology Screening.

    PubMed

    Kohsman, Mindy G

    2016-01-01

    Neonatal nurses frequently care for babies who have been exposed in utero to potentially harmful substances, both licit and illicit. The risks to the fetus from nicotine, marijuana, alcohol, and opiates are significant. Adverse effects from environmental factors may confound pharmacologic effects of substances. Nurses are called to shift the perception of substance use disorder from that of willful harm to the fetus to that of an opportunity to provide treatment assistance that can positively affect child health and development. Concerns for unethical practices in the toxicology screening of pregnant women and their babies by risk factors that are unproven or disproven are discussed, and three goals of toxicology screening based on the ethical principles of justice and beneficence are proposed. This article will help equip neonatal nurses to fulfill their professional responsibility to advocate for just screening and referral practices in their institutions and communities. PMID:27636690

  18. Detection of the effects of repeated dose combined propoxur and heavy metal exposure by measurement of certain toxicological, haematological and immune function parameters in rats.

    PubMed

    Institóris, L; Siroki, O; Undeger, U; Basaran, N; Banerjee, B D; Dési, I

    2001-06-21

    In the present study, an immunotoxicity test system, containing general toxicological (body weight gain, organ weights), haematological (WBC,RBC, Ht, mean cell volume of the RBCs, cell content of the femoral bone marrow), and immune function (PFC assay, DTH reaction) investigations, was used for detection the effects of a 4 weeks repeated low dose combined oral exposure of male Wistar rats with propoxur and the heavy metals arsenic or mercury. Two doses of the compounds were used: a higher one (the lowest dose which resulted in significant change of at least one parameter examined in previous dose-effect experiments), and a lower one (the highest dose which proved to be non-effective). The applied doses were: 8.51 and 0.851 mg kg(-1) of propoxur, 13.3 and 3.33 mg kg(-1) of NaAsO(2), and 3.20 and 0.40 mg kg(-1) of HgCl(2). In the combination treatment, the high dose of propoxur was combined with the low dose of arsenic or mercury, and the high doses of each heavy metals were combined with the low dose of propoxur. The main finding of this study was that some of the combinations significantly altered the relative weight of liver, adrenals and kidneys, related to both the untreated and the high dose internal control. Among the immune functions examined, only the PFC content of the spleen showed a trend of changes in certain combinations versus the corresponding high dose control. According to the present results, combined exposure with propoxur and the heavy metals examined can modify the detection limit of the single compounds and/or may alter their toxic effects.

  19. Toxicological benchmarks for screening of potential contaminants of concern for effects on aquatic biota on the Oak Ridge Reservation, Oak Ridge, Tennessee

    SciTech Connect

    Sutter, G.A. II ); Futrell, M.A. ); Kerchner, G.A. )

    1992-09-01

    This report presents potential screening benchmarks for protection of aquatic life from contaminants in water. Because there is no guidance for screening benchmarks, a set of alternative benchmarks is presented here. The alternative benchmarks are based on different conceptual approaches to estimating concentrations causing significant effects. For the upper screening benchmark, they are the acute National Ambient Water Quality Criterion (NAWQC) and the acute pesticide advisory value (a concentration that is estimated with 95% confidence not to exceed the unknown acute NAWQC for those chemicals with no NAWQC). The alternative chronic benchmarks are the chronic NAWQC, the chronic pesticide screening value, the lowest chronic values for fish and daphnids, the lowest concentration that produces a response in 20% of fish and daphnids [effective concentration 20 (EC[sub 20])] as established through chronic toxicity tests, the estimated EC[sub 20] for a sensitive species, and the concentration estimated to cause a 20% reduction in the recruit abundance of largemouth bass. It is recommended that ambient chemical concentrations be compared to all of these benchmarks. To the extent that toxicity data are available, this report presents the alternative benchmarks for chemicals that have been detected on the Oak Ridge Reservation. It also presents the data used to calculate the benchmarks, and the sources of the data. It compares the benchmarks and discusses their relative conservatism and utility.

  20. Efficacy and toxicological evaluation of Coccinia grandis (Cucurbitaceae) extract in male Wistar rats

    PubMed Central

    Attanayake, Anoja Priyadarshani; Jayatilaka, Kamani Ayoma Perera Wijewardena; Pathirana, Chitra; Mudduwa, Lakmini Kumari Boralugoda

    2013-01-01

    Objective To investigate the oral antihyperglycemic effect of aqueous leaf extract of Coccinia grandis (L.) (Cucurbitaceae) along with toxicological effects in alloxan induced diabetic and healthy Wistar rats. Methods A single graded dose of aqueous leaf extract of Coccinia grandis (0.25-2.00 g/kg) was administered orally to alloxan induced (150 mg/kg, i.p.) diabetic Wistar rats (n=6). In acute toxicity assessment, Wistar rats were administered the extract at the same dose range and observed for three days. Sub-chronic toxicity was evaluated by daily administration of the extract for 30 d at the dose which showed the optimum antihyperglycemic effect. Signs of toxicity, body weight of animals, consumption of food and water were monitored during the study period. The effects of the extract on biochemical (lipid parameters and activities of liver enzymes), hematological parameters (full blood count) and histopathological effects in organs were assessed at the end of the study. Results The optimum effective dose on glucose tolerance for Coccinia grandis leaf extract was found to be 0.75 g/kg in diabetic rats. The extract neither produced significant changes in consumption of food, intake of water, relative weight of organs nor affected biochemical, hematological and histopathological parameters (P<0.05). Conclusions The extract at a dose of 0.75 g/kg was found to be toxicologically safe as a potential antihyperglycemic agent in Wistar rats.

  1. Predictive Models and Computational Toxicology

    EPA Science Inventory

    Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The ToxCast computational toxicology research program was l...

  2. CHEMINFORMATIC APPROACHES IN PREDICTIVE TOXICOLOGY.

    EPA Science Inventory

    Cheminformatics and data models, are providing the underpinning for the large public HTS efforts of the NIH Molecular Libraries Initiative, as well as new toxicity-targeted HTS programs within the EPA and the NIEHS National Toxicology Program.

  3. Acute Effects of Marijuana Smoking on Negative and Positive Affect.

    PubMed

    Metrik, Jane; Kahler, Christopher W; McGeary, John E; Monti, Peter M; Rohsenow, Damaris J

    2011-02-01

    Human studies and animal experiments present a complex and often contradictory picture of the acute impact of marijuana on emotions. The few human studies specifically examining changes in negative affect find either increases or reductions following delta-9-tetrahydrocannabinol (THC) administration. In a 2 × 2, instructional set (told THC vs. told no THC) by drug administration (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, we examined the pharmacologic effect of marijuana on physiological and subjective stimulation, subjective intoxication, and self-reported negative and positive affect with 114 weekly marijuana smokers. Individuals were first tested under a baseline/no smoking condition and again under experimental condition. Relative to placebo, THC significantly increased arousal and confusion/bewilderment. However, the direction of effect on anxiety varied depending on instructional set: Anxiety increased after THC for those told placebo but decreased among other participants. Furthermore, marijuana users who expected more impairment from marijuana displayed more anxiety after smoking active marijuana, whereas those who did not expect the impairment became less anxious after marijuana. Both pharmacologic and stimulus expectancy main effects significantly increased positive affect. Frequent marijuana users were less anxious after smoking as compared to less frequent smokers. These findings show that expectancy instructions and pharmacology play independent roles in effects of marijuana on negative affect. Further studies examining how other individual difference factors impact marijuana's effects on mood are needed.

  4. Acute Effects of Marijuana Smoking on Negative and Positive Affect

    PubMed Central

    Metrik, Jane; Kahler, Christopher W.; McGeary, John E.; Monti, Peter M.; Rohsenow, Damaris J.

    2013-01-01

    Human studies and animal experiments present a complex and often contradictory picture of the acute impact of marijuana on emotions. The few human studies specifically examining changes in negative affect find either increases or reductions following delta-9-tetrahydrocannabinol (THC) administration. In a 2 × 2, instructional set (told THC vs. told no THC) by drug administration (smoked marijuana with 2.8% THC vs. placebo) between-subjects design, we examined the pharmacologic effect of marijuana on physiological and subjective stimulation, subjective intoxication, and self-reported negative and positive affect with 114 weekly marijuana smokers. Individuals were first tested under a baseline/no smoking condition and again under experimental condition. Relative to placebo, THC significantly increased arousal and confusion/bewilderment. However, the direction of effect on anxiety varied depending on instructional set: Anxiety increased after THC for those told placebo but decreased among other participants. Furthermore, marijuana users who expected more impairment from marijuana displayed more anxiety after smoking active marijuana, whereas those who did not expect the impairment became less anxious after marijuana. Both pharmacologic and stimulus expectancy main effects significantly increased positive affect. Frequent marijuana users were less anxious after smoking as compared to less frequent smokers. These findings show that expectancy instructions and pharmacology play independent roles in effects of marijuana on negative affect. Further studies examining how other individual difference factors impact marijuana's effects on mood are needed. PMID:24319318

  5. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

    PubMed

    Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

    2015-07-01

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

  6. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance.

    PubMed

    Baker, Lindsay B; Rollo, Ian; Stein, Kimberly W; Jeukendrup, Asker E

    2015-07-14

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1-2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30-60 g/h in the form of a 6%-7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a game

  7. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance

    PubMed Central

    Baker, Lindsay B.; Rollo, Ian; Stein, Kimberly W.; Jeukendrup, Asker E.

    2015-01-01

    Intermittent sports (e.g., team sports) are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1–2 h). Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1) potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2) the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3) what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports). Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30–60 g/h in the form of a 6%–7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before and during a

  8. 78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-26

    ... HUMAN SERVICES National Institutes of Health National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods; Announcement of Meeting; Request for Comments SUMMARY: This notice announces a meeting of the Scientific Advisory Committee on Alternative Toxicological...

  9. Current developments in toxicological research on arsenic

    PubMed Central

    Bolt, Hermann M.

    2013-01-01

    There is a plethora of recent publications on all aspects relevant to the toxicology of arsenic (As). Over centuries exposures to arsenic continue to be a major public health problem in many countries. In particular, the occurrence of high As concentrations in groundwater of Southeast Asia receives now much attention. Therefore, arsenic is a high-priority matter for toxicological research. Key exposure to As are (traditional) medicines, combustion of As-rich coal, presence of As in groundwater, and pollution due to mining activities. As-induced cardiovascular disorders and carcinogenesis present themselves as a major research focus. The high priority of this issue is now recognized politically in a number of countries, research funds have been made available. Also experimental research on toxicokinetics and toxicodynamics and on modes of toxic action is moving very rapidly. The matter is of high regulatory concern, and effective preventive measures are required in a number of countries. PMID:27092031

  10. Current developments in toxicological research on arsenic.

    PubMed

    Bolt, Hermann M

    2013-01-01

    There is a plethora of recent publications on all aspects relevant to the toxicology of arsenic (As). Over centuries exposures to arsenic continue to be a major public health problem in many countries. In particular, the occurrence of high As concentrations in groundwater of Southeast Asia receives now much attention. Therefore, arsenic is a high-priority matter for toxicological research. Key exposure to As are (traditional) medicines, combustion of As-rich coal, presence of As in groundwater, and pollution due to mining activities. As-induced cardiovascular disorders and carcinogenesis present themselves as a major research focus. The high priority of this issue is now recognized politically in a number of countries, research funds have been made available. Also experimental research on toxicokinetics and toxicodynamics and on modes of toxic action is moving very rapidly. The matter is of high regulatory concern, and effective preventive measures are required in a number of countries.

  11. Role of toxicological interactions in chemical carcinogenesis

    SciTech Connect

    Witschi, H.

    1984-01-01

    Toxicological interactions may occur not only when exposure to two or more chemicals is simultaneous, but also when exposures are separated in time. Often the sequence of exposure determines the nature of the toxicological response. This is illustrated with the two hindered phenolic antioxidants, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). Evidence available suggests that in certain tissues exposure to BHT first and then to a carcinogen is without significant consequences, whereas exposure to BHT after a carcinogen may enhance tumor formation. On the other hand, exposure to BHA before carcinogen administration often has a protective effect, whereas exposure to BHA after a carcinogen sometimes protects and sometimes is without any influence. Mechanisms underlying these interactions may be induction of mixed function oxidase, production of cell hyperplasia or other, as yet ill-defined, events such as modification of biological reactivity. 15 references, 5 figures, 1 table.

  12. Role of toxicological interactions in chemical carcinogenesis

    SciTech Connect

    Witschi, H.

    1983-01-01

    Toxicological interactions may occur not only when exposure to two or more chemicals is simultaneous, but also when exposures are separated in time. Often the sequence of exposure determines the nature of the toxicological response. This is illustrated with the two hindered phenolic antioxidants, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA). Evidence available suggests that in certain tissues exposure to BHT first and then to a carcinogen is without significant consequences, whereas exposure to BHT after a carcinogen may enhance tumor formation. On the other hand, exposure to BHA before carcinogen administration often has a protective effect, whereas exposure to BHA after a carcinogen sometimes protects and sometimes is without any influence. Mechanisms underlying these interactions may be induction of mixed function oxidases, production of cell hyperplasia or other, as yet ill-defined, events such as modification of biological reactivity.

  13. Avian Models in Teratology and Developmental Toxicology

    PubMed Central

    Smith, Susan M.; Flentke, George R.; Garic, Ana

    2015-01-01

    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high throughput. The chick genome is sequenced and significant molecular resources are available for study including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent’s embryotoxic effects. Here we present protocols for using avian embryos in toxicology research including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function. PMID:22669661

  14. Avian models in teratology and developmental toxicology.

    PubMed

    Smith, Susan M; Flentke, George R; Garic, Ana

    2012-01-01

    The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function.

  15. Toxicology of tetramethyltin and other organometals used in photovoltaic cell manufacture

    NASA Astrophysics Data System (ADS)

    Hamilton, L. D.; Medeiros, W. H.; Moskowitz, P. D.; Rybicka, K.

    1988-07-01

    In photovoltaic cell fabrication, organometals (alkyl metals) may be used in such processes as metalorganic chemical vapor deposition, transparent contact oxide deposition, doping, and ion implantation. Although these compounds offer potential performance advantages over earth metals and possibly greater safety in handling than metal hydrides, they are not without risk to health and property. Most organometals can ignite spontaneously in air. Some also react violently with water. Oxidation by-products from these reactions are hazardous to health. Of the organometals used in photovoltaic cell fabrication, only the toxicology of organotins (triethyl-, trimethyl- and tetramethyltin) was studied extensively. In mammalian systems, tetramethyltin is rapidly dealkylated to trimethyltin. Although tin was classified by some investigators as an essential trace element, the effects of organotin compounds on humans are poorly known. Animal studies show that the most prominent effects of trimethyltin are on the central nervous system. Several observations of poisoning were reported; effects ranged from reversible neurologic disorders to death. Limited available data suggest that humans respond to single acute doses and more alarmingly to repeated sub-toxic doses, suggesting a cumulative effect. Toxicologic properties of diethyltelluride also were evaluated in animal experiments. The compound had toxic effects on the blood, liver, kidney, heart, and skin. Based on these studies and others of related compounds (e.g., methylmercury, tributyltin) extreme caution should be exercised in using organometal compounds in photovoltaic cell manufacturing.

  16. Sudden unexpected death under acute influence of cannabis.

    PubMed

    Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

    2014-04-01

    The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. PMID:24598271

  17. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions

    SciTech Connect

    Wincent, Emma; Stegeman, John J.; Jönsson, Maria E.

    2015-04-15

    Wnt/β-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between β-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the β-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with β-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of β-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a β-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of β-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of β-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating β-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes.

  18. Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: implications for physiological and toxicological AHR functions

    PubMed Central

    Wincent, Emma; Stegeman, John J.; Jönsson, Maria E.

    2016-01-01

    Wnt/β-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between β-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the β-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB126). This led us to investigate AHR interaction with β-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of β-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a β-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholine-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of β-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of β-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating β-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes. PMID:25711857

  19. Biological markers of male reproductive toxicology

    SciTech Connect

    Ewing, L.L.; Mattison, D.R.

    1987-10-01

    Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

  20. Toxicological benchmarks for wildlife: 1994 Revision

    SciTech Connect

    Opresko, D.M.; Sample, B.E.; Suter, G.W. II

    1994-09-01

    The process by which ecological risks of environmental contaminants are evaluated is two-tiered. The first tier is a screening assessment where concentrations of contaminants in the environment are compared to toxicological benchmarks which represent concentrations of chemicals in environmental media (water, sediment, soil, food, etc.) that are presumed to be nonhazardous to the surrounding biota. The second tier is a baseline ecological risk assessment where toxicological benchmarks are one of several lines of evidence used to support or refute the presence of ecological effects. The report presents toxicological benchmarks for assessment of effects of 76 chemicals on 8 representative mammalian wildlife species and 31 chemicals on 9 avian wildlife species. The chemicals are some of those that occur at United States Department of Energy waste sites; the wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. Further descriptions of the chosen wildlife species and chemicals are provided in the report. The benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species. These benchmarks only consider contaminant exposure through oral ingestion of contaminated media; exposure through inhalation or direct dermal exposure are not considered in this report.

  1. Aflatoxin: A 50-Year Odyssey of Mechanistic and Translational Toxicology

    PubMed Central

    Kensler, Thomas W.; Roebuck, Bill D.; Wogan, Gerald N.; Groopman, John D.

    2011-01-01

    Since their discovery 50 years ago, the aflatoxins have become recognized as ubiquitous contaminants of the human food supply throughout the economically developing world. The adverse toxicological consequences of these compounds in populations are quite varied because of a wide range of exposures leading to acute effects, including rapid death, and chronic outcomes such as hepatocellular carcinoma. Furthermore, emerging studies describe a variety of general adverse health effects associated with aflatoxin, such as impaired growth in children. Aflatoxin exposures have also been demonstrated to multiplicatively increase the risk of liver cancer in people chronically infected with hepatitis B virus (HBV) illustrating the deleterious impact that even low toxin levels in the diet can pose for human health. The public health impact of aflatoxin exposure is pervasive. Aflatoxin biomarkers of internal and biologically effective doses have been integral to the establishment of the etiologic role of this toxin in human disease through better estimates of exposure, expanded knowledge of the mechanisms of disease pathogenesis, and as tools for implementing and evaluating preventive interventions. PMID:20881231

  2. Avian toxicologic diagnosis

    USGS Publications Warehouse

    Sigurdson, C.J.; Franson, J.C.; Fudge, A.M.

    2000-01-01

    This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

  3. WHY DO THE ACUTE BEHAVIORAL EFFECTS OT TOLUENE IN RATS DEPEND ON THE ROUTE OF EXPOSURE?

    EPA Science Inventory

    Despite evidence suggesting that the acute effects of organic solvents are related to their concentration in the brain, we have observed route-dependent differences in the acute behavioral effects of toluene. Whereas inhaled toluene disrupts the performance of rats on a visual si...

  4. Acute and Chronic Effects of Cocaine on the Spontaneous Behavior of Pigeons

    ERIC Educational Resources Information Center

    Pinkston, Jonathan W.; Branch, Marc N.

    2010-01-01

    The present experiment examined the effects of acute and daily cocaine on spontaneous behavior patterns of pigeons. After determining the acute effects of a range of doses, 9 pigeons were divided into three groups that received one of three doses of cocaine daily, either 1.0, 3.0, or 10.0 mg/kg cocaine. Measures were taken of spontaneous…

  5. Potential for genotoxic and reprotoxic effects of vanadium compounds due to occupational and environmental exposures: an article based on a presentation at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology, Washington DC, August 15-18, 2012.

    PubMed

    Altamirano-Lozano, M A; Álvarez-Barrera, L; Mateos-Nava, R A; Fortoul, T I; Rodríguez-Mercado, J J

    2014-01-01

    Research on the biological effects of vanadium in humans has shown that acute poisoning in workers can manifest itself in a number of symptoms. There are no reports in humans about reproductive and developmental effects induced by vanadium compounds in humans; however, some studies with rats and mice indicate that vanadium can cross the placental barrier and accumulate in fetal membranes rather than the fetus itself. In this case, probably most consequences of administration of vanadium to pregnant females like reabsorptions, fetal death and reduction in size can be the result of maternal toxicity. Concerning genetic and related effects in humans exposed to different vanadium compounds, data are controversial. Data on genotoxic effects in workers exposed to vanadium indicate that they can have an increased risk to develop cancer, and DNA instability can give rise to an onset of genetic syndromes, fetal malformations, and cancer. This paper presents materials presented at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology in a session titled 'Relationship between occupational and environmental exposure to vanadium compounds and the reprotoxic and genotoxic effects'.

  6. Effects of acute restraint stress on set-shifting and reversal learning in male rats.

    PubMed

    Thai, Chester A; Zhang, Ying; Howland, John G

    2013-03-01

    Exposure to acute stress alters cognition; however, few studies have examined the effects of acute stress on executive functions such as behavioral flexibility. The goal of the present experiments was to determine the effects of acute periods of stress on two distinct forms of behavioral flexibility: set-shifting and reversal learning. Male Sprague-Dawley rats were trained and tested in an operant-chamber-based task. Some of the rats were exposed to acute restraint stress (30 min) immediately before either the set-shifting test day or the reversal learning test day. Acute stress had no effect on set-shifting, but it significantly facilitated reversal learning, as assessed by both trials to criterion and total errors. In a second experiment, the roles of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the acute-stress-induced facilitation of reversal learning were examined. Systemic administration of the GR-selective antagonist RU38486 (10 mg/kg) or the MR-selective antagonist spironolactone (50 mg/kg) 30 min prior to acute stress failed to block the facilitation on reversal learning. The present results demonstrate a dissociable effect of acute stress on set-shifting and reversal learning and suggest that the facilitation of reversal learning by acute stress may be mediated by factors other than corticosterone.

  7. Introduction: biomarkers in neurodevelopment toxicology

    SciTech Connect

    Needleman, H.L.

    1987-10-01

    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  8. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    PubMed Central

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases. PMID:24179466

  9. Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms

    PubMed Central

    Nie, Wenna; Lv, Yana; Yan, Leyu; Chen, Xi; Lv, Haitao

    2015-01-01

    Aristolochic acid (AA) is the major active component of medicinal plants from the Aristolochiaceae family of flowering plants widely utilized for medicinal purposes. However, the molecular mechanisms of AA systems effects remain poorly understood. Here, we employed a joint network analysis that combines network pharmacology, a protein–protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects. Firstly, we selected 15 protein targets (14 genes) in the PubChem database as the potential target genes and used PPI knowledge to incorporate these genes into an AA-specific gene network that contains 129 genes. Secondly, we performed biological processes analysis for these AA-related targets using ClueGO, some of new targeted genes were randomly selected and experimentally verified by employing the Quantitative Real-Time PCR assay for targeting the systems effects of AA in HK-2 cells with observed dependency of concentration. Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA. At last, we built an AA target pathway network of significant pathways to predict the system effects. Taken together, this joint network analysis revealed that the systematic regulatory effects of AA on multidimensional pathways involving both therapeutic action and toxicity. PMID:26620132

  10. Toxicology as a nanoscience? – Disciplinary identities reconsidered

    PubMed Central

    Kurath, Monika; Maasen, Sabine

    2006-01-01

    Toxicology is about to establish itself as a leading scientific discipline in addressing potential health effects of materials on the nanosize level. Entering into a cutting-edge field, has an impact on identity-building processes within the involved academic fields. In our study, we analyzed the ways in which the entry into the field of nanosciences impacts on the formation of disciplinary identities. Using the methods of qualitative interviews with particle toxicologists in Germany, Holland, Switzerland and the USA, we could demonstrate that currently, toxicology finds itself in a transitional phase. The development of its disciplinary identity is not yet clear. Nearly all of our interview partners stressed the necessity of repositioning toxicology. However, they each suggested different approaches. While one part is already propagandizing the establishment of a new discipline – 'nanotoxicology'- others are more reserved and are demanding a clear separation of traditional and new research areas. In phases of disciplinary new-orientation, research communities do not act consistently. Rather, they establish diverse options. By expanding its disciplinary boundaries, participating in new research fields, while continuing its previous research, and only vaguely defining its topics, toxicology is feeling its way into the new fields without giving up its present self-conception. However, the toxicological research community is also discussing a new disciplinary identity. Within this, toxicology could develop from an auxiliary into a constitutive position, and take over a basic role in the cognitive, institutional and social framing of the nanosciences. PMID:16646961

  11. Toxicology of sulfur in ruminants: review

    SciTech Connect

    Kandylis, K.

    1984-10-01

    This review deals with the toxicology of sulfur in ruminants including toxicity, neurotoxic effects, and mechanism of toxic action of hydrogen sulfide, clinical signs, and treatment. It will report effects of excessive intake of sulfur by ruminants on feed intake, animal performance, ruminal digestion and motility, rumination, and other physiological functions. Poisoning of animals with sulfur from industrial emissions (sulfur dioxide) also is discussed. Excessive quantities of dietary sulfur (above .3 to .4%) as sulfate or elemental sulfur may cause toxic effects and in extreme cases can be fatal. The means is discussed whereby consumption of excessive amounts of sulfur leads to toxic effects. 53 references, 1 table.

  12. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights.

    PubMed

    Denkins, P; Badhwar, G; Obot, V; Wilson, B; Jejelewo, O

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  13. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

    NASA Technical Reports Server (NTRS)

    Denkins, P.; Badhwar, G.; Obot, V.; Wilson, B.; Jejelewo, O.

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  14. Toxicological effects, mechanisms, and implied toxicity thresholds in the roots of Vicia faba L. seedlings grown in copper-contaminated soil.

    PubMed

    Xu, Xianghua; Huang, Zhicheng; Wang, Chengrun; Zhong, Li; Tian, Yuan; Li, Dongdong; Zhang, Gaojian; Shi, Jian

    2015-09-01

    Copper (Cu) contamination has become a global concern because of industrial, agricultural, and other anthropogenic activities. In the present experiments, the toxicological effects, mechanisms, and potential toxicity thresholds were investigated in the roots of Vicia faba L. seedlings that were cultivated in Cu-amended soils (0, 6.25, 12.5, 25, 50, 100, 200, 400, and 600 mg kg(-1)) for 20 days, based on an analysis of the soil physicochemical properties, native Cu, available Cu, and root-enriched Cu contents. The superoxide dismutase (SOD), ascorbate peroxidase (APX), and guaiacol peroxidase (POD) isozymes and activities, as well as glutathione (GSH) and heat shock protein 70 (HSP70), changed like biphasic dose-response curves, cooperating to control the redox homeostasis. The APX and POD enzymes exhibited enhanced activities and became H2O2 scavengers primarily when the catalase (CAT) activities tended to decrease. Endoprotease (EP) isozymes and activities might be enhanced to degrade carbonylated proteins and alleviate metabolic disturbance in the roots. Additionally, HSP70 may not be suitable as a biomarker for relatively higher soil Cu concentrations and relatively longer exposure times for the roots. As a result, the isozymes and activities of SOD, CAT, and EP, as well as GSH, can be adopted as the most sensitive biomarkers. The toxicity threshold is estimated as 0.76-1.21 mg kg(-1) of available Cu in the soils or 25.04-36.65 μg Cu g(-1) dry weights (DW) in the roots.

  15. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights.

    PubMed

    Denkins, P; Badhwar, G; Obot, V; Wilson, B; Jejelewo, O

    2001-01-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  16. Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

    NASA Astrophysics Data System (ADS)

    Denkins, Pamela; Badhwar, Gautam; Obot, Victor; Wilson, Bobby; Jejelewo, Olufisayo

    2001-08-01

    NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far, the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space, exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation

  17. Antitumoral effect of Ocoxin on acute myeloid leukemia

    PubMed Central

    Díaz-Rodríguez, Elena; Hernández-García, Susana; Sanz, Eduardo; Pandiella, Atanasio

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy whose incidence is growing in developed countries. In the relapse setting, very limited therapeutic options are available and in most cases only palliative care can be offered to patients. The effect of a composite formulation that contains several antioxidants, Ocoxin Oral solution (OOS), was tested in this condition. When analyzed in vitro, OOS exhibited anti-AML action that was both time and dose dependent. In vivo OOS induced a ralentization of tumor growth that was due to a decrease in cell proliferation. Such effect could, at least partially, be due to an increase in the cell cycle inhibitor p27, although other cell cycle proteins seemed to be altered. Besides, OOS induced an immunomodulatory effect through the induction of IL6. When tested in combination with other therapeutic agents normally used in the treatment of AML patients, OOS demonstrated a higher antiproliferative action, suggesting that it may be used in combination with those standard of care treatments to potentiate their antiproliferative action in the AML clinic. PMID:26756220

  18. Antidepressant Effects of Mallotus oppositifolius in Acute Murine Models

    PubMed Central

    Kukuia, Kennedy K. E.; Mante, Priscilla K.; Ameyaw, Elvis O.; Adongo, Donatus W.

    2014-01-01

    Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a plant used for CNS conditions in Ghana, was investigated for acute antidepressant effects in the forced swimming (FST) and tail suspension tests (TST). Results. In both FST and TST, MOE (10, 30, and 100 mg kg−1) significantly decreased immobility periods and frequencies. A 3-day pretreatment with 200 mg kg−1, i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, reversed the decline in immobility and the increase of swimming score induced by MOE in the modified FST. Pretreatment with reserpine alone (1 mg kg−1), α-methyldopa alone (400 mg kg−1, i.p.), or a combination of both drugs failed to reverse the decline in immobility or the increase in swimming score caused by the extract in the modified FST. The extract potentiated the frequency of head twitch responses induced by 5-hydroxytryptamine. Pretreatment with d-serine (600 mg kg−1, i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while d-cycloserine (2.5 mg kg−1, i.p.), a glycine/NMDA partial agonist, potentiated it in both TST and modified FST. Conclusion. The extract exhibited antidepressant effects in mice which is mediated by enhancement of serotoninergic neurotransmission and inhibition of glycine/NMDA receptor activation. PMID:25045543

  19. Diversity and variability of the effects of nicotine on different cortical regions of the brain - therapeutic and toxicological implications.

    PubMed

    Toledano, Adolfo; Alvarez, María-Isabel; Toledano-Díaz, Adolfo

    2010-09-01

    Nicotine/nicotine agonists or allosteric modulators of nicotine receptors have been suggested as the most important therapeutic agents in the prevention and clinical control of cognitive impairment which characterize neuropsychiatric and neurodegenerative disorders such as schizophrenia, attention deficit/hyperactivity disorder and Alzheimer's disease. Both clinical studies and animal experiments support the important role of the nicotinic systems in learning, different kind of memory and cognition. For development of nicotinic treatments we have a well characterized lead compound, nicotine. However, the neural nicotinic mechanisms underlying cognitive functions are not well known because the side effects of nicotine overdose have hindered the development of this therapeutical line. The new development of non-toxic, brain specific nicotine drugs need a full knowledge of these mechanism and a reevaluation of the nicotine effects. This review aims to analyze the different kind of effects of nicotine on the Central Nervous System (CNS), especially on the cortex and hippocampus. Nicotine effects are, theoretically and/or practically, of variable character depending on daily dose and time of treatment; on the subtype and density of the different nicotinic receptors existing in the distinct brain regions; on the processes of desensitization and tolerance of nicotinic receptors and on other neuronal factors. Nicotine produces the above mentioned activation of the cognitive functions acting directly or indirectly on cortical neurons. In some experiments, high doses of nicotine can impair memory. This substance induces increases in the glycolytic pathway and Krebs cycle of neurons, as well as brain blood flow. Nicotine also produces an increase in NGF immunoreactivity in frontoparietal cortex. All these neuronal changes may cause different positive effects such as neuroprotection, neuroplasticity and better performance of synaptic circuits. The benefit of other neuronal

  20. A multi-analyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat

    EPA Science Inventory

    The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte pro...

  1. Love Canal: environmental and toxicological studies

    SciTech Connect

    Kim, C.S.

    1981-01-01

    The New York State Department of Health has been involved at the Love Canal since 1978. The State has carried out numerous environmental and toxicological studies. The major purposes for these studies were to define how Love Canal contaminants might be escaping into the environment at large, what paths contaminant migration might take, and what toxicological effects Love Canal chemicals might have individually and together. Although underground contaminant migration was hypothesized along swales and underground utility bedding, these mechanisms have been proven not to be operative except for some migration along the utility bedding under Frontier Avenue. In general no underground migration has occurred outside the confines of the three city blocks that contain the Love Canal referred to as the ''first ring''. Studies have been confused by apparent burial of waste materials in areas proximate but not directly connected to the Love Canal. Migration of Love Canal leachate has occurred through storm sewers. Love Canal contaminants have reached creeks to the north and the Niagara River to the south through storm sewer transport. In spite of finding 2, 3, 7, 8 tetrachlorodibenzoparadioxin (TCDD), toxicological studies in situ and through exposure to volatile components in Love Canal soils do not indicate unusual toxicity. Animal studies continue in an attempt to determine the teratogenic and fetotoxic potential of Love Canal chemicals under different routes of exposure.

  2. PPARα mediates acute effects of palmitoylethanolamide on sensory neurons

    PubMed Central

    Khasabova, Iryna A.; Xiong, Yee; Coicou, Lia G.; Piomelli, Daniele; Seybold, Virginia

    2012-01-01

    The amplitude of the depolarization-evoked Ca2+ transient is larger in dorsal root ganglion (DRG) neurons from tumor-bearing mice compared to that of neurons from naive mice, and the change is mimicked by co-culturing DRG neurons with the fibrosarcoma cells used to generate the tumors (Khasabova et al., 2007). The effect of palmitoylethanolamide (PEA), a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), was determined on the evoked-Ca2+ transient in the co-culture condition. The level of PEA was reduced in DRG cells from tumor-bearing mice as well as those co-cultured with fibrosarcoma cells. Pretreatment with PEA, a synthetic PPARα agonist (GW7647), or ARN077, an inhibitor of the enzyme that hydrolyses PEA, acutely decreased the amplitude of the evoked Ca2+ transient in small DRG neurons co-cultured with fibrosarcoma cells. The PPARα antagonist GW6471 blocked the effect of each. In contrast, the PPARα agonist was without effect in the control condition, but the antagonist increased the amplitude of the Ca2+ transient suggesting that PPARα receptors are saturated by endogenous ligand under basal conditions. Effects of drugs on mechanical sensitivity in vivo paralleled their effects on DRG neurons in vitro. Local injection of ARN077 decreased mechanical hyperalgesia in tumor-bearing mice, and the effect was blocked by GW6471. These data support the conclusion that the activity of DRG neurons is rapidly modulated by PEA through a PPARα-dependent mechanism. Moreover, agents that increase the activity of PPARα may provide a therapeutic strategy to reduce tumor-evoked pain. PMID:22972997

  3. [Acute Toxic Effects of Bromate on Aquatic Organisms].

    PubMed

    Wang, Zhi-wei; Liu, Dong-mei; Zhang, Wen-juan; Cui, Fu-yi

    2016-02-15

    Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID:27363170

  4. Toxicologic studies associated with the agricultural use of municipal sewage sludge and health effects among sewage treatment plant workers.

    PubMed

    Babish, J G; Stoewsand, G S; Kranz, J M; Boyd, J N; Ahrens, V D; Lisk, D J

    1984-09-01

    The proposed use of municipal sewage sludges as soil amendments on agricultural land involves potential health risks. Sludges may contain toxic heavy metals, synthetic organics, and pathogens. Studies of animals inhabiting sludge-amended soils, or foraging on crops grown on such soils, have shown an increased deposition of cadmium and polychlorinated biphenyls in animal tissues, hepatic microsomal enzyme induction, altered blood profiles, appearance of mutagens in blood and excreta, and lowered feed intake, feed efficiency, and milk production. Epidemiologic evidence of possible adverse health effects among sewage plant workers exposed to aerosolized pathogens or synthetic organic vapors during wastewater treatment or land spreading of sludge is still inconclusive. Other possible deleterious environmental effects include pollution of groundwater and toxicity to birds consuming worms or insects inhabiting sludge-treated soils.

  5. Toxicological effects of bisphenol A on growth and antioxidant defense system in Oryza sativa as revealed by ultrastructure analysis.

    PubMed

    Ali, Imran; Liu, Bohan; Farooq, Muhammad Ahsan; Islam, Faisal; Azizullah, Azizullah; Yu, Chunyan; Su, Wen; Gan, Yinbo

    2016-02-01

    The present study was conducted to evaluate the effect of bisphenol A (BPA) on rice seedlings grown in a hydroponic system. The obtained results demonstrated that at lower concentration (up to 10µM) BPA had some stimulatory effects on the growth of rice seedlings but at higher doses it significantly inhibited seedlings growth. The photosynthetic pigments were significantly decreased by high doses of BPA. Exposure to BPA caused increased membrane permeability in root cells and resulted in increased concentration of reactive oxygen species (ROS) and increased lipid peroxidation as revealed by thiobarbituric acid reactive substances (TBARS) assay. In leaves, superoxide dismutase (SOD) activity exhibited an increase at lower concentrations of BPA but was inhibited at the highest dose (200µM) of BPA. At 100µM of BPA, a significant increase in antioxidant activities in leaves was observed but at 200µM this activity was inhibited. In roots, a significant decrease in enzymes activity was recorded at the highest concentration of BPA (200µM); however, ascorbate peroxidase (APX) and catalase (CAT) activities were significantly increased at the concentrations of 10 and 50µM in comparison to the control. Moreover, the present results revealed that BPA severely affected cell organelles in rice seedlings. It can be concluded that the observed adverse effects in rice seedlings by BPA in the present study could be attributed to the oxidative stress caused by BPA. PMID:26547398

  6. Sensory and Cognitive Effects of Acute Exposure to Hydrogen Sulfide

    PubMed Central

    Fiedler, Nancy; Kipen, Howard; Ohman-Strickland, Pamela; Zhang, Junfeng; Weisel, Clifford; Laumbach, Robert; Kelly-McNeil, Kathie; Olejeme, Kelechi; Lioy, Paul

    2008-01-01

    Background Some epidemiologic studies have reported compromised cognitive and sensory performance among individuals exposed to low concentrations of hydrogen sulfide (H2S). Objectives We hypothesized a dose–response increase in symptom severity and reduction in sensory and cognitive performance in response to controlled H2S exposures. Methods In separate exposure sessions administered in random order over three consecutive weeks, 74 healthy subjects [35 females, 39 males; mean age (± SD) = 24.7 ± 4.2; mean years of education = 16.5 ± 2.4], were exposed to 0.05, 0.5, and 5 ppm H2S. During each exposure session, subjects completed ratings and tests before H2S exposure (baseline) and during the final hour of the 2-hr exposure period. Results Dose–response reduction in air quality and increases in ratings of odor intensity, irritation, and unpleasantness were observed. Total symptom severity was not significantly elevated across any exposure condition, but anxiety symptoms were significantly greater in the 5-ppm than in the 0.05-ppm condition. No dose–response effect was observed for sensory or cognitive measures. Verbal learning was compromised during each exposure condition. Conclusions Although some symptoms increased with exposure, the magnitude of these changes was relatively minor. Increased anxiety was significantly related to ratings of irritation due to odor. Whether the effect on verbal learning represents a threshold effect of H2S or an effect due to fatigue across exposure requires further investigation. These acute effects in a healthy sample cannot be directly generalized to communities where individuals have other health conditions and concomitant exposures. PMID:18197303

  7. Toxicology of the nasal passages

    SciTech Connect

    Barrow, C.S.

    1986-01-01

    Contents of this work include: Comparative Anatomy and Function of the Nasal Passages; Light Microscopic Examination of the Rat Nasal Passages: Preparation and Morphologic Features; Histopathology of Acute and Subacute Nasal Toxicity; Pathology of Chronic Nasal Toxic Responses Including Cancer; Responses of the Nasal Mucociliary Apparatus to Airborne Irritants; Effects of Chemical Exposure on Olfaction in Humans, Possible Consequences of Cytochrome P-450-Dependent Monooxygenases in Nasal Tissues.

  8. Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

    PubMed Central

    Valdes, J J; Cameron, J E; Cole, R J

    1985-01-01

    Tremorgenic mycotoxins induce neurologic symptoms ranging from mental confusion to tremors, seizures and death, and are apparently the only class of mycotoxins with significant central nervous system activity. Tremorgens have been implicated in a number of neurologic diseases of cattle collectively known as staggers syndromes, and pose significant agricultural and health problems for both cattle and humans. Although the effects of tremorgens are thought to result from transient perturbations of amino acid neurotransmitter release mechanisms, there is reason to believe that acute exposures to toxins with such synaptic effects may result in degeneration of neuronal fiber processes. To test this hypothesis, rats were given a single tremorgenic (3 mg/kg, IP) dose of aflatrem, and kinetics of amino acid neurotransmitter uptake was assessed in isolated hippocampal nerve terminals at 1 day, 1 week, and 2 weeks after injection. Results indicate a decrease in the capacity of the GABA and glutamate uptake systems, which was interpreted as a loss of nerve terminals. The affinity constants suggest a decrease in release of these transmitters as well. In addition to its transient influence on transmitter release, a single low dose of aflatrem is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems and therefore represents a long-term health threat. PMID:2867895

  9. Designed Synthesis of CeO2 Nanorods and Nanowires for Studying Toxicological Effects of High Aspect Ratio Nanomaterials

    PubMed Central

    Ji, Zhaoxia; Wang, Xiang; Zhang, Haiyuan; Lin, Sijie; Meng, Huan; Sun, Bingbing; George, Saji; Xia, Tian; Nel, André E.; Zink, Jeffrey I.

    2012-01-01

    While it has been shown that high aspect ratio nanomaterials like carbon nanotubes and TiO2 nanowires can induce toxicity by acting as fiber-like substances that damage the lysosome, it is not clear what the critical lengths and aspect ratios are that induce this type of toxicity. To answer this question, we synthesized a series of cerium oxide (CeO2) nanorods and nanowires with precisely controlled lengths and aspect ratios. Both phosphate and chloride ions were shown to play critical roles in obtaining these high aspect ratio nanostructures. High resolution TEM analysis shows that single crystalline CeO2 nanorods/nanowires were formed along the [211] direction by an “oriented attachment” mechanism, followed by Ostwald ripening. The successful creation of a comprehensive CeO2 nanorod/nanowire combinatorial library allows, for the first time, the systematic study of the effect of aspect ratio on lysosomal damage, cytoxicity and IL-1β production by the human myeloid cell line (THP-1). This in vitro toxicity study demonstrated that at lengths ≥200 nm and aspect ratios ≥ 22, CeO2 nanorods induced progressive cytotoxicity and pro-inflammatory effects. The relatively low “critical” length and aspect ratio were associated with small nanorod/nanowire diameters (6–10 nm), which facilitates the formation of stacking bundles due to strong van der Waals and dipole-dipole attractions. Our results suggest that both length and diameter components of aspect ratio should be considered when addressing the cytotoxic effects of long aspect ratio materials. PMID:22564147

  10. Toxicological effects of fumonisin B1 alone and in combination with other fusariotoxins on bovine granulosa cells.

    PubMed

    Albonico, Marco; Schütz, Luis F; Caloni, Francesca; Cortinovis, Cristina; Spicer, Leon J

    2016-08-01

    There is now overwhelming evidence of global contamination of commodities with Fusarium mycotoxins. Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON), α-zearalenol (α-ZEA) and β-zearalenol (β-ZEA). The aim of this study was to determine if FB1, alone and combined with DON or α-ZEA or β-ZEA, can affect cell proliferation and steroid production of bovine granulosa cells (GC). A species-specific model with bovine granulosa cells (GC) was used to study the potential endocrine disruptor effects of FB1 alone and in co-exposure. In the presence of β-ZEA (30 ng/mL), FB1 at 30 ng/mL showed a stimulatory effect on GC numbers. Insulin-like growth factor-1 (IGF1)-stimulated cell proliferation was decreased after exposure to β-ZEA alone at 5.0 μg/mL and FB1 with α-ZEA and β-ZEA at the same concentration. Regarding steroid production, FB1 at 30 ng/mL and 100 ng/mL amplified the inhibitory effect of β-ZEA (30 ng/mL) on estradiol (E2) production, while FB1 alone increased (P < 0.05) IGF1-induced E2 production. α-ZEA alone decreased (P < 0.05) E2 production, whereas β-ZEA alone and in combination with FB1 decreased (P < 0.05) E2 production. These studies indicate for the first time that the Fusarium mycotoxin FB1 along with other mycotoxins can affect GC proliferation and steroid production, which ultimately could influence reproductive function in cattle.

  11. Toxicological effects of the sunscreen UV filter, benzophenone-2, on planulae and in vitro cells of the coral, Stylophora pistillata.

    PubMed

    Downs, C A; Kramarsky-Winter, Esti; Fauth, John E; Segal, Roee; Bronstein, Omri; Jeger, Rina; Lichtenfeld, Yona; Woodley, Cheryl M; Pennington, Paul; Kushmaro, Ariel; Loya, Yossi

    2014-03-01

    Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an "emerging contaminant of concern" that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death.The LC50 of BP-2 in the light for an 8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion (ppb), respectively. The LC50s for BP-2 in darkness for the same time points were 144 parts per million and 548 parts per billion [corrected].

  12. Toxicological Effect of Manganese on NF-κB/iNOS-COX-2 Signaling Pathway in Chicken Testes.

    PubMed

    Du, Ye; Zhu, Yihao; Teng, Xiaojie; Zhang, Kun; Teng, Xiaohua; Li, Shu

    2015-11-01

    Manganese (Mn) pollution can cause tissue and organ dysfunction and structural damage. The toxicity of Mn in poultry was reported, but inflammatory damage that Mn induced in the testicular tissue has not been reported. The aim of this study was to investigate the effect of Mn poisoning on NF-κB/iNOS-COX-2 signaling pathway in chicken testes. One hundred eighty Hyline male chickens at 7 days of age were fed either commercial diet or MnCl2-added commercial diet containing 600, 900, and 1800 mg/kg Mn for 30, 60, and 90 days, respectively. The messenger RNA (mRNA) expression of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), nitric oxide (NO) content, iNOS activity, and histopathology were examined in chicken testes. The results showed that excess Mn upregulated mRNA expression of NF-κB, COX-2, TNF-α, and iNOS, NO content, and iNOS activity at 60th and 90th day. Mn had a time-dependent effect on NF-κB and TNF-α mRNA expression. Mn had a dose- and time-dependent effect on NO content and iNOS activity. Mn exposure induced chicken testis histological changes in dose- and time-dependent manner. It indicated that Mn exposure resulted in inflammatory injury of chicken testis tissue through NF-κB/iNOS-COX-2 signaling pathway.

  13. Toxicological effects of the sunscreen UV filter, benzophenone-2, on planulae and in vitro cells of the coral, Stylophora pistillata.

    PubMed

    Downs, C A; Kramarsky-Winter, Esti; Fauth, John E; Segal, Roee; Bronstein, Omri; Jeger, Rina; Lichtenfeld, Yona; Woodley, Cheryl M; Pennington, Paul; Kushmaro, Ariel; Loya, Yossi

    2014-03-01

    Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an "emerging contaminant of concern" that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death.The LC50 of BP-2 in the light for an 8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion (ppb), respectively. The LC50s for BP-2 in darkness for the same time points were 144 parts per million and 548 parts per billion [corrected]. PMID:24352829

  14. Toxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Soil and Litter Invertebrates and Heterotrophic Process

    SciTech Connect

    Will, M.E.

    1994-01-01

    This report presents a standard method for deriving benchmarks for the purpose of ''contaminant screening,'' performed by comparing measured ambient concentrations of chemicals. The work was performed under Work Breakdown Structure 1.4.12.2.3.04.07.02 (Activity Data Sheet 8304). In addition, this report presents sets of data concerning the effects of chemicals in soil on invertebrates and soil microbial processes, benchmarks for chemicals potentially associated with United States Department of Energy sites, and literature describing the experiments from which data were drawn for benchmark derivation.

  15. Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin®) and metallic silver.

    PubMed

    Whitehouse, Michael; Butters, Desley; Vernon-Roberts, Barrie

    2013-08-01

    This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag°) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag° were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin(®)) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag° or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995

  16. Reproductive toxicology of nickel - review.

    PubMed

    Forgacs, Zsolt; Massányi, Peter; Lukac, Norbert; Somosy, Zoltan

    2012-01-01

    The goal of this minireview is to summarize our current knowledge on the reproductive toxicity of soluble nickel salts. We made an attempt to present the most relevant data obtained from in vivo and in vitro experiments performed on mammals, mammalian primary cell cultures and cell lines. Nickel has been demonstrated to disturb the mammalian reproductive functions at several levels of regulation. The results of previous investigations indicate that the hormonal effects may play an important role in the reproductive toxicology of nickel both at the neuroendocrine and gonadal levels in the hypothalamic-pituitary-gonadal (HPG) axis. At the molecular level, it may be important that nickel may substitute certain other metals in metal dependent enzymes, leading to an altered protein function. It readily crosses the cell membrane via calcium channels and competes with calcium for specific receptors. Nickel can cross-link aminoacids to DNA, lead to formation of reactive oxygen species (ROS), moreover mimic hypoxia. These changes may lead to the activation of some signaling pathways, subsequent transcription factors and eventually to alterations in gene expression and cellular metabolism. These events are likely to be involved in the reproductive toxicity of nickel.

  17. Toxicological and biochemical analyses demonstrate no toxic effect of Cry1C and Cry2A to Folsomia candida

    PubMed Central

    Yang, Yan; Chen, Xiuping; Cheng, Lisheng; Cao, Fengqin; Romeis, Jörg; Li, Yunhe; Peng, Yufa

    2015-01-01

    Collembolans are common soil arthropods that may be exposed to insecticidal proteins produced in genetically engineered (GE) plants by ingestion of crop residues or root exudates. In the present study, a dietary exposure assay was validated and used to assess the lethal and sublethal effects of two Bacillus thuringiensis (Bt) insecticidal proteins, Cry1C and Cry2A, on Folsomia candida. Using the insecticidal compounds potassium arsenate (PA), protease inhibitor (E-64), and Galanthus nivalis agglutinin (GNA) mixed into Baker’s yeast, we show that the assay used can detect adverse effects on F. candida. Survival and development were significantly reduced when F. candida was fed a diet containing PA, E-64, and GNA at 9, 75, and 100 μg/g diet, respectively, but not when fed a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A. The activities of test antioxidant-, detoxification-, and digestion-related enzymes in F. candida were unaltered by a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A, but were significantly increased by a diet containing 75 μg/g E-64. The results confirm that Cry1C and Cry2A are not toxic to F. candida at concentrations that are much higher than those encountered under field conditions. PMID:26494315

  18. Toxicological and biochemical analyses demonstrate no toxic effect of Cry1C and Cry2A to Folsomia candida.

    PubMed

    Yang, Yan; Chen, Xiuping; Cheng, Lisheng; Cao, Fengqin; Romeis, Jörg; Li, Yunhe; Peng, Yufa

    2015-01-01

    Collembolans are common soil arthropods that may be exposed to insecticidal proteins produced in genetically engineered (GE) plants by ingestion of crop residues or root exudates. In the present study, a dietary exposure assay was validated and used to assess the lethal and sublethal effects of two Bacillus thuringiensis (Bt) insecticidal proteins, Cry1C and Cry2A, on Folsomia candida. Using the insecticidal compounds potassium arsenate (PA), protease inhibitor (E-64), and Galanthus nivalis agglutinin (GNA) mixed into Baker's yeast, we show that the assay used can detect adverse effects on F. candida. Survival and development were significantly reduced when F. candida was fed a diet containing PA, E-64, and GNA at 9, 75, and 100 μg/g diet, respectively, but not when fed a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A. The activities of test antioxidant-, detoxification-, and digestion-related enzymes in F. candida were unaltered by a diet containing 300 μg/g Cry1C or 600 μg/g Cry2A, but were significantly increased by a diet containing 75 μg/g E-64. The results confirm that Cry1C and Cry2A are not toxic to F. candida at concentrations that are much higher than those encountered under field conditions. PMID:26494315

  19. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-26

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy.

  20. Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?

    PubMed

    Moraga, Felipe; Ahumada, Vanessa; Crovari, Fernando

    2016-01-01

    Acute appendicitis is a common cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, growing evidence has been published about the use of antibiotics as the exclusive treatment for acute appendicitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded the use of antibiotics to treat acute uncomplicated appendicitis may be less effective than appendectomy and probably increases major complications compared with appendectomy. PMID:26817927

  1. Ship diesel emission aerosols: A comprehensive study on the chemical composition, the physical properties and the molecular biological and toxicological effects on human lung cells of aerosols from a ship diesel engine operated with heavy or light diesel fuel oil

    NASA Astrophysics Data System (ADS)

    Zimmermann, R.; Buters, J.; Öder, S.; Dietmar, G.; Kanashova, T.; Paur, H.; Dilger, M.; Mülhopt, S.; Harndorf, H.; Stengel, B.; Rabe, R.; Hirvonen, M.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Berube, K.; Sippula, O.; Streibel, T.; Karg, E.; Schnelle-Kreis, J.; Lintelmann, J.; Sklorz, M.; Arteaga Salas, M.; Orasche, J.; Müller, L.; Reda, A.; Passig, J.; Radischat, C.; Gröger, T.; Weiss, C.

    2013-12-01

    The Virtual Helmholtz Institute-HICE (www.hice-vi.eu) addresses chemical & physical properties, transformation processes and health effects of anthropogenic combustion emissions. This is performed by thorough comprehensive chemical and physical characterization of combustion aerosols (including application of advantageous on-line methods) and studying of biological effects on human lung cell-cultures. A new ALI air-liquid-interface (ALI) exposition system and a mobile S2-biological laboratory were developed for the HICE-measurements. Human alveolar basal epithelial cells (A549 etc.) are ALI-exposed to fresh, diluted (1:40-1:100) combustion aerosols and subsequently were toxicologically and molecular-biologically characterized (e.g. proteomics). By using stable isotope labeling technologies (13C-Glucose/metabolomics; 2H-Lysine/SILAC-proteomics), high sensitivity and accuracy for detection of molecular-biological effects is achievable even at sub-toxic effect dose levels. Aerosols from wood combustion and ship diesel engine (heavy/light fuel oil) have been investigated. The effect of wood combustion and ship diesel PM e.g. on the protein expression of ALI-exposed A549 cells was compared. Filtered aerosol is used as gas-reference for the isotope labeling based method (SILAC). Therefore the effects of wood combustion- and shipping diesel-PM can be directly compared. Ship diesel aerosol causes a broader distribution in the observed fold changes (log2), i.e. more proteins are significantly up-/down-regulated in case of shipping diesel PM-exposure. This corresponds to a stronger biological reaction if compared to wood combustion-PM exposure. The chemical analysis results on wood combustion- and ship diesel-PM depict more polycyclic aromatic hydrocarbons (PAH)/oxidized-PAH but less of some transition metals (V, Fe) in the wood combustion case. Interestingly, alkylated PAH are considerably more abundant in shipping PM, suggesting that PAH/Oxy-PAH may be less relevant for

  2. Toxicological evaluation of sediment samples spiked with human pharmaceutical products: Energy status and neuroendocrine effects in marine polychaetes Hediste diversicolor.

    PubMed

    Maranho, L A; André, C; DelValls, T A; Gagné, F; Martín-Díaz, M L

    2015-08-01

    There is a lack of studies about the ecotoxicology of pharmaceutical products on marine environment. To predict possible adverse effects of pharmaceutical products on benthic biota, polychaetes Hediste diversicolor were exposed for 14-days to pharmaceutical-spiked sediments under laboratory conditions. Carbamazepine (CBZ), ibuprofen (IBP) and propranolol (PRO) at concentrations of 500ngg(-1), 50ngg(-1), 5ngg(-1), 0.5ngg(-1) and 0.05ngg(-1), fluoxetine (FX) and 17α-ethynylestradiol (EE2) at concentrations of 100ngg(-1), 10ngg(-1), 1ngg(-1), 0.1ngg(-1) and 0.01ngg(-1), including environmental concentrations (underlined), were spiked in marine sediment samples. After the exposure, cellular energy status (total lipids content - TLP; and mitochondrial electron transport activity - MET), metabolism of monoamines (monoamine oxidase activity - MAO) and inflammation properties (cyclooxygenase activity - COX) were observed in polychaetes. CBZ increased TLP content and MET activity, and decreased MAO activity in polychaetes. IBP did not interfere on the TLP level, but on the MET and MAO activities (environmental concentrations). FX did not cause changes in the energy status. Therefore, environmental concentration diminished MAO activity. EE2 did not affect the energy status, however, MAO activity was significantly lower in polychaetes exposed to environmental concentration. PRO increased TLP level in polychaetes, but not MET activity. MAO activity was significantly lower for polychaetes exposed to environmental concentration. Except FX, all pharmaceuticals showed anti-inflammatory properties confirmed by the decrease of COX activity. Pharmaceutical products affected H. diversicolor physiology and health. As a benthic top predator, adverse effects on sea-worms can potentially culminate in ecosystem perturbations.

  3. In silico toxicology for the pharmaceutical sciences.

    PubMed

    Valerio, Luis G

    2009-12-15

    The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

  4. In silico toxicology for the pharmaceutical sciences

    SciTech Connect

    Valerio, Luis G.

    2009-12-15

    The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy of in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical

  5. Acute effects of acrolein in human volunteers during controlled exposure

    PubMed Central

    Dwivedi, Aishwarya M.; Johanson, Gunnar; Lorentzen, Johnny C.; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Abstract Context: Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. Objective: The aim of the study was to determine thresholds for acute irritation for acrolein. Methods: Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. Results: The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p < 0.001, Friedman test) with a median rating of 8 mm (corresponding to “hardly at all”) at the 0.1 ppm condition and with no influence from EA. No significant exposure-related effects were found for pulmonary function, or nasal swelling, nor for markers of inflammation and coagulation in blood (IL-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor, and Clara cell protein) or induced sputum (cell count, differential cell count, IL-6 and IL-8). Blink frequency recorded by electromyography was increased during exposure to 0.1 ppm acrolein alone but not during any of the other five exposure conditions. Conclusion: Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein. PMID:26635308

  6. Acute effects of tianeptine on circulating neurotransmitters and cardiovascular parameters.

    PubMed

    Lechin, Fuad; van der Dijs, Bertha; Hernández, Gerardo; Orozco, Beatriz; Rodríguez, Simon; Baez, Scarlet

    2006-03-01

    Tianeptine is a serotonin-uptake enhancer drug whose antidepressant effectiveness is based on its ability to reduce rather than increase serotonin availability at the synaptic cleft. This paradoxical neuropharmacological mechanism has raised doubt among neuropharmacologists and psychiatrists as to the role of tianeptine as a trusty-reliable antidepressant drug. This controversial issue led us to investigate the acute effects of a single, oral dose (12.5 mg) of this drug on circulating neurotransmitters and cardiovascular parameters in 50 healthy subjects. The drug provoked a striking and significant reduction of plasma noradrenaline (NA) and plasma serotonin (f-5-HT) while it increased plasma dopamine (DA) and platelet serotonin (p-5-HT) concentrations within the 4-h study period. No adrenaline (Ad) changes were registered. The NA/Ad ratio and the f-5-HT/p-5-HT ratio showed significant reduction throughout the test. Finally, although diastolic blood pressure (DBP) showed significant decrease, neither systolic blood pressure (SBP) nor heart rate (HR) showed significant change. These findings are consistent with the postulation that tianeptine reduces both neural sympathetic activity and parasympathetic activity without affecting adrenal sympathetic activity, enabling us to discuss the possible mechanisms involved in the antidepressant effects of tianeptine. The well-known fact that major depressed patients always show raised NA plus lower than normal p-5-HT levels, both disorders which are normalized by tianeptine, gives neurochemical support to the clinical improvement triggered by the drug in these patients. Summarizing, the results presented in this study demonstrate that tianeptine triggers significant reduction of circulating noradrenaline and plasma serotonin while increasing circulating dopamine and platelet serotonin. Other possible neuropharmacological effects are also discussed.

  7. Implications of the Differential Toxicological Effects of III-V Ionic and Particulate Materials for Hazard Assessment of Semiconductor Slurries.

    PubMed

    Jiang, Wen; Lin, Sijie; Chang, Chong Hyun; Ji, Zhaoxia; Sun, Bingbing; Wang, Xiang; Li, Ruibin; Pon, Nanetta; Xia, Tian; Nel, André E

    2015-12-22

    Because of tunable band gaps, high carrier mobility, and low-energy consumption rates, III-V materials are attractive for use in semiconductor wafers. However, these wafers require chemical mechanical planarization (CMP) for polishing, which leads to the generation of large quantities of hazardous waste including particulate and ionic III-V debris. Although the toxic effects of micron-sized III-V materials have been studied in vivo, no comprehensive assessment has been undertaken to elucidate the hazardous effects of submicron particulates and released III-V ionic components. Since III-V materials may contribute disproportionately to the hazard of CMP slurries, we obtained GaP, InP, GaAs, and InAs as micron- (0.2-3 μm) and nanoscale (<100 nm) particles for comparative studies of their cytotoxic potential in macrophage (THP-1) and lung epithelial (BEAS-2B) cell lines. We found that nanosized III-V arsenides, including GaAs and InAs, could induce significantly more cytotoxicity over a 24-72 h observation period. In contrast, GaP and InP particulates of all sizes as well as ionic GaCl3 and InCl3 were substantially less hazardous. The principal mechanism of III-V arsenide nanoparticle toxicity is dissolution and shedding of toxic As(III) and, to a lesser extent, As(V) ions. GaAs dissolves in the cell culture medium as well as in acidifying intracellular compartments, while InAs dissolves (more slowly) inside cells. Chelation of released As by 2,3-dimercapto-1-propanesulfonic acid interfered in GaAs toxicity. Collectively, these results demonstrate that III-V arsenides, GaAs and InAs nanoparticles, contribute in a major way to the toxicity of III-V materials that could appear in slurries. This finding is of importance for considering how to deal with the hazard potential of CMP slurries.

  8. Influence of a municipal solid waste landfill in the surrounding environment: toxicological risk and odor nuisance effects.

    PubMed

    Palmiotto, Marinella; Fattore, Elena; Paiano, Viviana; Celeste, Giorgio; Colombo, Andrea; Davoli, Enrico

    2014-07-01

    The large amounts of treated waste materials and the complex biological and physicochemical processes make the areas in the proximity of landfills vulnerable not only to emissions of potential toxic compounds but also to nuisance such as odor pollution. All these factors have a dramatic impact in the local environment producing environmental quality degradation. Most of the human health problems come from the landfill gas, from its non-methanic volatile organic compounds and from hazardous air pollutants. In addition several odorants are released during landfill operations and uncontrolled emissions. In this work we present an integrated risk assessment for emissions of hazard compounds and odor nuisance, to describe environmental quality in the landfill proximity. The study was based on sampling campaigns to acquire emission data for polychlorinated dibenzo-p-dioxins and dibenzofurans, dioxin-like polychlorobiphenyls, polycyclic aromatic hydrocarbons, benzene and vinyl chloride monomer and odor. All concentration values in the emissions from the landfill were measured and used in an air dispersion model to estimate maximum concentrations and depositions in correspondence to five sensitive receptors located in proximity of the landfill. Results for the different scenarios and cancer and non-cancer effects always showed risk estimates which were orders of magnitude below those accepted from the main international agencies (WHO, US EPA). Odor pollution was significant for a limited downwind area near the landfill appearing to be a significant risk factor of the damage to the local environment.

  9. Toxicological benchmarks for screening potential contaminants of concern for effects on soil and litter invertebrates and heterotrophic process

    SciTech Connect

    Will, M.E.; Suter, G.W. II

    1994-09-01

    One of the initial stages in ecological risk assessments for hazardous waste sites is the screening of contaminants to determine which of them are worthy of further consideration as {open_quotes}contaminants of potential concern.{close_quotes} This process is termed {open_quotes}contaminant screening.{close_quotes} It is performed by comparing measured ambient concentrations of chemicals to benchmark concentrations. Currently, no standard benchmark concentrations exist for assessing contaminants in soil with respect to their toxicity to soil- and litter-dwelling invertebrates, including earthworms, other micro- and macroinvertebrates, or heterotrophic bacteria and fungi. This report presents a standard method for deriving benchmarks for this purpose, sets of data concerning effects of chemicals in soil on invertebrates and soil microbial processes, and benchmarks for chemicals potentially associated with United States Department of Energy sites. In addition, literature describing the experiments from which data were drawn for benchmark derivation. Chemicals that are found in soil at concentrations exceeding both the benchmarks and the background concentration for the soil type should be considered contaminants of potential concern.

  10. Toxicological effects of red wine, orange juice, and other dietary SULT1A inhibitors via excess catecholamines.

    PubMed

    Eagle, Ken

    2012-06-01

    SULT1A enzymes protect humans from catecholamines, but natural substances in many foods have been found to inhibit these enzymes in vitro. Given the hormonal roles of catecholamines, any in vivo SULT1A inhibition could have serious consequences. This paper uses a re-analysis of published data to confirm that SULT1A inhibitors have effect in vivo in at least some patients. Nineteen studies are cited that show ingestion of SULT1A inhibitors leading to catecholamine increases, blood pressure changes, migraine headaches, or atrial fibrillation. SULT1A inhibition does not create the catecholamines, but prevents normal catecholamine deactivation. Susceptible patients probably have lower-activity SULT1A alleles. The paper discusses new hypotheses that SULT1A inhibition can cause "holiday heart" arrhythmias and type 2 diabetes in susceptible patients. Subgroup analysis based on SULT1A alleles, and addition of a catecholamine source, should improve the consistency of results from tests of SULT1A inhibitors. SULT1A inhibition may be a key contributor to cheese-induced migraines (via annatto), false positives in metanephrine testing, and the cardiovascular impacts of recreational alcohols.

  11. Serum Metabolomics in Rats after Acute Paraquat Poisoning.

    PubMed

    Wang, Zhiyi; Ma, Jianshe; Zhang, Meiling; Wen, Congcong; Huang, Xueli; Sun, Fa; Wang, Shuanghu; Hu, Lufeng; Lin, Guanyang; Wang, Xianqin

    2015-01-01

    Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers. PMID:26133715

  12. Toxicological effects of particulate matter (PM2.5) on rats: Bioaccumulation, antioxidant alterations, lipid damage, and ABC transporter activity.

    PubMed

    Ribeiro, Joaquim de Paula; Kalb, Ana Cristina; Campos, Paula Peixoto; Cruz, Alex Rubén Huaman De La; Martinez, Pablo Elias; Gioda, Adriana; Souza, Marta Marques de; Gioda, Carolina Rosa

    2016-11-01

    Previous studies have demonstrated the harmful effects of atmospheric pollutants on cardiac systems because of the presence of particulate matter (PM), a complex mixture of numerous substances including trace metals. In this study, the toxicity of PM2.5 from two regions, rural (PM2.5 level of 8.5 ± 4.0 μg m(-3)) and industrial (PM2.5 level of 14.4 ± 4.1 μg m(-3)) in Brazil, was investigated through in vivo experiments in rats. Metal accumulation and biochemical responses were evaluated after rats were exposed to three different concentrations of PM2.5 in saline extract (10× dilution, 5× dilution, and concentrated). The experimental data showed the bioaccumulation of diverse trace metals in the hearts of groups exposed to PM2.5 from both regions. Furthermore, mobilization of the antioxidant defenses and an increase in lipid peroxidation of the cardiac tissue was observed in response to the industrial and rural area PM2.5. Glutathione-S-transferase activity was increased in groups exposed to the 5× and concentrated rural PM2.5. Additionally, ATP-binding cassette (ABC) transporter activity in the cardiac tissue exposed to PM2.5 was reduced in response to the 5× dilution of the rural and industrial region PM2.5. Histological analysis showed a decrease in the percentage of cardiac cells in the heart at all tested concentrations. The results indicate that exposure to different concentrations of PM2.5 from both sources causes biochemical and histological changes in the heart with consequent damage to biological structures; these factors can favor the development of cardiac diseases.

  13. Toxicological effects of selective herbicides on plant growth promoting activities of phosphate solubilizing Klebsiella sp. strain PS19.

    PubMed

    Ahemad, Munees; Saghir Khan, Md

    2011-02-01

    This study examines the effect of four herbicides, quizalafop-p-ethyl, clodinafop, metribuzin and glyphosate, on plant growth promoting activities like phosphate solubilization, siderophores, indole acetic acid, exo-polysaccharides, hydrogen cyanide and ammonia production by herbicide tolerant Klebsiella sp. strain PS19. The strain was isolated from mustard rhizosphere. The selected herbicides were applied two to three times at the recommended rates. Klebsiella sp. strain PS19 tolerated a concentration of 1600 μg/ml each of quizalafop-p-ethyl and clodinafop, and 3200 and 2800 μg/ml of metribuzin and glyphosate, respectively. The activities of Klebsiella sp. strain PS19 observed under in vitro environment were persistent in the presence of all herbicides at lower rates. The plant growth promoting activities even-though decreased regularly, but was not lost completely, as the concentration of each herbicide was increased from the recommended to three times of higher doses. Among all herbicides, quizalafop-p-ethyl, generally, showed maximum toxicity to plant growth promoting activities of Klebsiella sp. strain PS19. As an example, 40, 80 and 120 μg/l of quizalafop-p-ethyl added to liquid culture Pikovskaya medium, decreased phosphate solubilizing activity of strain PS19 by 93, 95 and 97%, respectively over untreated control. The study revealed that the higher rates of herbicides though decreased the plant growth promoting activity but it did not completely inhibit the metabolic activities of strain PS19. The herbicide tolerance together with growth promoting activities observed under herbicide stress suggests that Klebsiella sp. strain PS19 could be used as bacterial preparation for facilitating the growth and yields of crops even in soils polluted with herbicides.

  14. Toxicological effects of selective herbicides on plant growth promoting activities of phosphate solubilizing Klebsiella sp. strain PS19.

    PubMed

    Ahemad, Munees; Saghir Khan, Md

    2011-02-01

    This study examines the effect of four herbicides, quizalafop-p-ethyl, clodinafop, metribuzin and glyphosate, on plant growth promoting activities like phosphate solubilization, siderophores, indole acetic acid, exo-polysaccharides, hydrogen cyanide and ammonia production by herbicide tolerant Klebsiella sp. strain PS19. The strain was isolated from mustard rhizosphere. The selected herbicides were applied two to three times at the recommended rates. Klebsiella sp. strain PS19 tolerated a concentration of 1600 μg/ml each of quizalafop-p-ethyl and clodinafop, and 3200 and 2800 μg/ml of metribuzin and glyphosate, respectively. The activities of Klebsiella sp. strain PS19 observed under in vitro environment were persistent in the presence of all herbicides at lower rates. The plant growth promoting activities even-though decreased regularly, but was not lost completely, as the concentration of each herbicide was increased from the recommended to three times of higher doses. Among all herbicides, quizalafop-p-ethyl, generally, showed maximum toxicity to plant growth promoting activities of Klebsiella sp. strain PS19. As an example, 40, 80 and 120 μg/l of quizalafop-p-ethyl added to liquid culture Pikovskaya medium, decreased phosphate solubilizing activity of strain PS19 by 93, 95 and 97%, respectively over untreated control. The study revealed that the higher rates of herbicides though decreased the plant growth promoting activity but it did not completely inhibit the metabolic activities of strain PS19. The herbicide tolerance together with growth promoting activities observed under herbicide stress suggests that Klebsiella sp. strain PS19 could be used as bacterial preparation for facilitating the growth and yields of crops even in soils polluted with herbicides. PMID:20721665

  15. Toxicological effects of particulate matter (PM2.5) on rats: Bioaccumulation, antioxidant alterations, lipid damage, and ABC transporter activity.

    PubMed

    Ribeiro, Joaquim de Paula; Kalb, Ana Cristina; Campos, Paula Peixoto; Cruz, Alex Rubén Huaman De La; Martinez, Pablo Elias; Gioda, Adriana; Souza, Marta Marques de; Gioda, Carolina Rosa

    2016-11-01

    Previous studies have demonstrated the harmful effects of atmospheric pollutants on cardiac systems because of the presence of particulate matter (PM), a complex mixture of numerous substances including trace metals. In this study, the toxicity of PM2.5 from two regions, rural (PM2.5 level of 8.5 ± 4.0 μg m(-3)) and industrial (PM2.5 level of 14.4 ± 4.1 μg m(-3)) in Brazil, was investigated through in vivo experiments in rats. Metal accumulation and biochemical responses were evaluated after rats were exposed to three different concentrations of PM2.5 in saline extract (10× dilution, 5× dilution, and concentrated). The experimental data showed the bioaccumulation of diverse trace metals in the hearts of groups exposed to PM2.5 from both regions. Furthermore, mobilization of the antioxidant defenses and an increase in lipid peroxidation of the cardiac tissue was observed in response to the industrial and rural area PM2.5. Glutathione-S-transferase activity was increased in groups exposed to the 5× and concentrated rural PM2.5. Additionally, ATP-binding cassette (ABC) transporter activity in the cardiac tissue exposed to PM2.5 was reduced in response to the 5× dilution of the rural and industrial region PM2.5. Histological analysis showed a decrease in the percentage of cardiac cells in the heart at all tested concentrations. The results indicate that exposure to different concentrations of PM2.5 from both sources causes biochemical and histological changes in the heart with consequent damage to biological structures; these factors can favor the development of cardiac diseases. PMID:27567156

  16. The New Designer Drug Wave: A Clinical, Toxicological, and Legal Analysis.

    PubMed

    Abbott, Ryan; Smith, David E

    2015-01-01

    This article reviews clinical, toxicological, and legal issues related to designer drug abuse, with a focus on synthetic cathinones (bath salts). Synthetic cathinones are amphetamine-type central nervous system (CNS) stimulants that produce similar effects to amphetamine. Like amphetamine, synthetic cathinones can also result in neurological and cardiovascular side-effects consistent with sympathomimetic toxicity. The differential for a patient presenting with the signs and symptoms of synthetic cathinone toxicity is broad, and laboratory testing for synthetic cathinones is of limited value in acute management. If a diagnosis of cathinone-induced delirium is suspected, treatment efforts should focus on controlling agitation and then treating medical complications such as metabolic acidosis. Physicians should be aware of these new drugs, not only to optimally treat patients, but also to raise awareness of the dangers of designer drug use through patient counseling and community outreach programs.

  17. The New Designer Drug Wave: A Clinical, Toxicological, and Legal Analysis.

    PubMed

    Abbott, Ryan; Smith, David E

    2015-01-01

    This article reviews clinical, toxicological, and legal issues related to designer drug abuse, with a focus on synthetic cathinones (bath salts). Synthetic cathinones are amphetamine-type central nervous system (CNS) stimulants that produce similar effects to amphetamine. Like amphetamine, synthetic cathinones can also result in neurological and cardiovascular side-effects consistent with sympathomimetic toxicity. The differential for a patient presenting with the signs and symptoms of synthetic cathinone toxicity is broad, and laboratory testing for synthetic cathinones is of limited value in acute management. If a diagnosis of cathinone-induced delirium is suspected, treatment efforts should focus on controlling agitation and then treating medical complications such as metabolic acidosis. Physicians should be aware of these new drugs, not only to optimally treat patients, but also to raise awareness of the dangers of designer drug use through patient counseling and community outreach programs. PMID:26579784

  18. Effective management of acute deep vein thrombosis: direct oral anticoagulants.

    PubMed

    Roussin, A

    2015-02-01

    Deep vein thrombosis (DVT) is a manifestation of venous thromboembolism (VTE) and accounts for most venous thromboembolic events. Although DVT is not directly life-threatening, thrombi in the proximal veins of the leg can embolize to the lungs to form a pulmonary embolism, which may prove rapidly fatal. If untreated, DVT can also lead to significant morbidity, including development of post-thrombotic syndrome. Among many risk factors, surgery, hospitalization, older age and active cancer increase the risk of VTE, and a previous event increases the risk of recurrence. Early detection and effective clot resolution are vital in managing DVT. Conventional approaches to acute treatment of VTE involve initial fast-acting parenteral heparin overlapping with and followed by vitamin K antagonist therapy. However, vitamin K antagonists have a narrow therapeutic window, require regular monitoring, and have multiple food and drug interactions. Results from phase III clinical studies involving direct Factor Xa and IIa inhibitors suggest that these agents provide an alternative therapeutic option that overcomes some of the complications associated with conventional treatment with predictable pharmacological properties and convenient dosing schedules. Analysis of data from the rivaroxaban EINSTEIN studies also suggests that these agents have the potential to improve patient-reported treatment satisfaction and reduce the length of hospital stay compared with conventional therapy. This review considers these treatment options, suitable treatment durations to prevent recurrence, and the management of DVT treatment in challenging patient groups. PMID:24927023

  19. Acute respiratory effects of summer smog in primary school children.

    PubMed

    Cuijpers, C E; Swaen, G M; Wesseling, G; Wouters, E F

    1994-06-01

    In 535 primary school children we studied the effects of exposure to summer smog on respiratory health. Baseline measurements were performed during low air pollution levels (max. 24-h concentrations of SO2, O3 and NO2 were 55, 49 and 58 micrograms/m3, respectively) consisting of lung function measurements using spirometry and the forced oscillation technique (FOT) and the prevalence of respiratory symptoms, determined by a written questionnaire. During a summer smog episode, 212 randomly chosen children were re-examined, characterised by 8-h ozone levels > 120 micrograms/m3 (max. 163 micrograms/m3) and 1-h ozone levels > 160 micrograms/m3 (max. 215 micrograms/m3). Overall, small decrements were observed in the forced expiratory volume in 1 s (FEV1), (P < 0.05) and the forced expiratory volume between 25 and 75% of the vital capacity (FEF25-75%) (P < 0.01). On the contrary, there was a statistically significant decrease in resistance parameters. No increases were observed in the prevalence of acute respiratory symptoms. In conclusion, in this study we found small inconsistent changes in lung function and no increase of respiratory symptoms after short-time exposure to moderately high ozone levels.

  20. Acute effects of ethanol on left ventricular diastolic function.

    PubMed Central

    Kupari, M; Koskinen, P; Hynynen, M; Salmenperä, M; Ventilä, M

    1990-01-01

    Transmitral flow velocities were measured by Doppler echocardiography in nine healthy men who ingested 1 g/kg of ethanol within one hour. The measurements were made before the first drink and every hour thereafter for three hours. The peak mean (SE) blood ethanol concentration was 21.4 (1.0) mmol/l. Each man was also studied after drinking fruit juice. Ethanol increased the heart rate but did not change the peak transmitral velocities, the normalised peak filling rate, the deceleration of early flow, or the duration of relaxation as measured from the second heart sound to the peak early diastolic velocity. The ratio of the peak atrial to the peak early diastolic velocity rose from 0.41 (0.03) to 0.44 (0.03) after ethanol but remained unchanged after juice. The difference between juice and ethanol was independent of changes in heart rate. The fluid balance was more negative in the ethanol experiment (-727 (114) ml v -107 (70) ml), suggesting a reduction in preload, and the ethanol-induced net loss of fluid correlated with the concomitant change in the velocity ratio. A moderate dose of ethanol causes a small acute increase of the ratio of the peak atrial to the peak early diastolic velocity of mitral flow in healthy subjects. Although this change indicates altered diastolic function of the left ventricle, most of it may result from the diuretic effect of ethanol. Any major impairment of ventricular relaxation seems unlikely. PMID:2393610

  1. Effects of acute spinalization on neurons of postural networks

    PubMed Central

    Zelenin, Pavel V.; Lyalka, Vladimir F.; Hsu, Li-Ju; Orlovsky, Grigori N.; Deliagina, Tatiana G.

    2016-01-01

    Postural limb reflexes (PLRs) represent a substantial component of postural corrections. Spinalization results in loss of postural functions, including disappearance of PLRs. The aim of the present study was to characterize the effects of acute spinalization on two populations of spinal neurons (F and E) mediating PLRs, which we characterized previously. For this purpose, in decerebrate rabbits spinalized at T12, responses of interneurons from L5 to stimulation causing PLRs before spinalization, were recorded. The results were compared to control data obtained in our previous study. We found that spinalization affected the distribution of F- and E-neurons across the spinal grey matter, caused a significant decrease in their activity, as well as disturbances in processing of posture-related sensory inputs. A two-fold decrease in the proportion of F-neurons in the intermediate grey matter was observed. Location of populations of F- and E-neurons exhibiting significant decrease in their activity was determined. A dramatic decrease of the efficacy of sensory input from the ipsilateral limb to F-neurons, and from the contralateral limb to E-neurons was found. These changes in operation of postural networks underlie the loss of postural control after spinalization, and represent a starting point for the development of spasticity. PMID:27302149

  2. Acute ethanol effects on focal cerebral ischemia in fasted rats.

    PubMed

    Zhao, Y J; Yang, G Y; Ben-Joseph, O; Ross, B D; Chenevert, T L; Domino, E F

    1998-05-01

    The effects of acute ethanol intoxication were investigated in a rat model of unilateral middle cerebral artery occlusion. Groups of 5 to 8 male Sprague-Dawley rats were subjected to 4 hr of left middle cerebral artery occlusion. All groups were deprived of food overnight and were pretreated intraperitoneally with 5% dextrose solution (10 ml/kg), 20% ethyl alcohol in 5% dextrose solution (2 g/kg), or 30% ethyl alcohol in a 5% dextrose solution (3 g/kg) 1 hr before middle cerebral artery occlusion. Regional cerebral blood flow during ipsilateral occlusion was approximately 9.1 to 10% of baseline in all groups. The mean % brain water content in control, 2 g/kg ethanol-treated groups, and 3 g/kg ethanol-treated groups were: in the ischemic core--81.6, 81.2, and 82.4; intermediate zone--80.5, 80.6, and 81.7; and outer zone--79.7, 79.7, and 80.8, respectively. Brain Na+ and K+ content in the three groups was related to water content, but much greater with ethanol pretreatment. The water content of the intermediate zones in the 3 g/kg ethanol-treated animals was significantly greater than in the control (p < 0.01 and 0.001) and the 2 g/kg ethanol-treated groups. One-way analysis of variance indicated a significant dose-effect relationship in which the lower dose of ethanol tended to reduce ischemic core water content, and the larger dose increased ischemic core water, compared with the control. None of the overnight fasted groups had any significant hyperglycemia. The group given 3 g/kg i.p. ethanol 1 hr before had exacerbated edema formation with a mean whole blood level of ethanol of approximately 230 mg/dl. The neurotoxic effects of high concentrations of ethanol were unrelated to any change in plasma glucose concentrations.

  3. Protective Effects of Hydrogen Gas on Experimental Acute Pancreatitis

    PubMed Central

    Zhou, Hao-xin; Han, Bing; Hou, Li-Min; An, Ting-Ting; Jia, Guang; Cheng, Zhuo-Xin; Ma, Yong; Zhou, Yi-Nan; Kong, Rui; Wang, Shuang-Jia; Wang, Yong-Wei; Sun, Xue-Jun; Pan, Shang-Ha; Sun, Bei

    2016-01-01

    Acute pancreatitis (AP) is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2) is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight). Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP. PMID:27115738

  4. Acute effect of ephedrine on 24-h energy balance

    NASA Technical Reports Server (NTRS)

    Shannon, J. R.; Gottesdiener, K.; Jordan, J.; Chen, K.; Flattery, S.; Larson, P. J.; Candelore, M. R.; Gertz, B.; Robertson, D.; Sun, M.

    1999-01-01

    Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

  5. The effects of acute hyperinsulinemia on bone metabolism

    PubMed Central

    Ivaska, Kaisa K; Heliövaara, Maikki K; Ebeling, Pertti; Bucci, Marco; Huovinen, Ville; Väänänen, H Kalervo; Nuutila, Pirjo; Koistinen, Heikki A

    2015-01-01

    Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m2 per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m2 per min) for 4 h resulted in more pronounced decrease (−32%, P<0.01) whereas shorter insulin exposure (40 mU/m2 per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin. PMID:26047829

  6. Toxicological assessment of polyhexamethylene biguanide for water treatment

    PubMed Central

    Mahmood, Abdulai Seidu; Awortwe, Charles; Nyarko, Alexander K.

    2015-01-01

    Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer's instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4x103 mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of PHMB to make water potable. PMID:27486381

  7. Toxicological assessment of polyhexamethylene biguanide for water treatment.

    PubMed

    Asiedu-Gyekye, Isaac J; Mahmood, Abdulai Seidu; Awortwe, Charles; Nyarko, Alexander K

    2015-12-01

    Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a stomach tube as per the manufacturer's instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4x10(3) mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of PHMB to make water potable. PMID:27486381

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

    PubMed

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

    2003-05-01

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

  9. Effect of fluid ingestion on orthostatic responses following acute exercise

    NASA Technical Reports Server (NTRS)

    Davis, J. E.; Fortney, S. M.

    1997-01-01

    Orthostatic tolerance is impaired following an acute bout of exercise. This study examined the effect of fluid ingestion following treadmill exercise in restoring the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/- 3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0 to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60 minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE) consisted of water-ingestion equivalent to 50% of the body weight lost during exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/- 1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs 6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58 +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition. Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic blood pressure, and total peripheral resistance responses to LBNP, but did not influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8 +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion on improving orthostatic responses following exercise, and suggest that dehydration is a contributing factor to orthostatic intolerance following exercise.

  10. Shoreline ecology program for Prince William Sound, Alaska, following the Exxon Valdez oil spill. Part 2: Chemistry and toxicology

    SciTech Connect

    Boehm, P.D.; Page, D.S.; Gilfillan, E.S.; Stubblefield, W.A.; Harner, E.J.

    1995-12-31

    This paper describes chemical and toxicological results of a comprehensive shoreline ecology program that was designed to assess recovery in Prince William Sound following the Exxon Valdez oil spill of March 24, 1989. The program is an application of the sediment quality triad approach, combining chemical, toxicological, and biological measurements. The study was designed so that results could be extrapolated to the entire spill zone in the sound and projected forward in time. It combined one-time sampling of 64 randomly chosen study sites representing four major habitats and four oiling levels (including unoiled reference sites), with periodic sampling at 12 subjectively chosen fixed sites. Sediment samples--or when conditions required, filter-wipes from rock surfaces--were collected in each of three intertidal zones and from subtidal stations up to 30-m deep. Oil removal was generally quite rapid: by 1991 the concentration of oil spilled from the Exxon Valdez had been dramatically reduced on the majority of shorelines by both natural processes and cleanup efforts. Acute sediment toxicity from oil (as measured by standard toxicity tests) was virtually absent by 1990--91, except at a small number of isolated locations. The petroleum residues had degraded below the threshold of acute toxic effects. Measurable polycyclic aromatic hydrocarbon (PAH) levels are, in general, well below those conservatively associated with adverse effects, and biological recovery has been considerably more rapid than the removal of the last chemical remnants. 55 refs., 15 figs., 4 tabs.

  11. The toxicological properties of petroleum gases.

    PubMed

    McKee, Richard H; Herron, Deborah; Saperstein, Mark; Podhasky, Paula; Hoffman, Gary M; Roberts, Linda

    2014-01-01

    To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition.

  12. The toxicological properties of petroleum gases.

    PubMed

    McKee, Richard H; Herron, Deborah; Saperstein, Mark; Podhasky, Paula; Hoffman, Gary M; Roberts, Linda

    2014-01-01

    To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition. PMID:24179026

  13. 42 CFR 493.1213 - Condition: Toxicology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Toxicology. 493.1213 Section 493.1213 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1213 Condition: Toxicology. If the laboratory provides services in the subspecialty of Toxicology,...

  14. 42 CFR 493.1213 - Condition: Toxicology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Toxicology. 493.1213 Section 493.1213 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1213 Condition: Toxicology. If the laboratory provides services in the subspecialty of Toxicology,...

  15. New research avenues in toxicology: 7-gas N-Gas Model, toxicant suppressants, and genetic toxicology.

    PubMed

    Levin, B C

    1996-12-31

    Three research areas -- a 7-gas N-Gas Model, toxicant suppressants, and genetic toxicology -- are presented as new research approaches in toxicology. The current 6-gas N-Gas Model predicts the toxic potency of the combustion products of materials based on the toxicological interactions of the fire gases carbon monoxide (CO), carbon dioxide (CO2), low oxygen (O2) concentrations, hydrogen cyanide (HCN), hydrogen chloride, and hydrogen bromide. The present research includes nitrogen dioxide (NO2) in a new 7-gas model which incorporates the synergistic effects of NO2 and CO2, the antagonistic effects of NO2 and HCN, and the additive effects of NO2 with CO and low O2. The area of toxicant suppressants concerns chemicals, which when added to a material, will inhibit or reduce the concentration of a specific toxic gas normally generated during thermal decomposition of that material. The effectiveness of this approach was demonstrated at the US National Institute of Standards and Technology when HCN generation was reduced by 90% and the resultant toxicity of the combustion products was lowered by 50% when a flexible polyurethane (FPU) foam was treated with 0.1% (by weight) cuprous oxide (Cu2O). Although melamine-treated FPU foams are being promoted as more fire safe than standard foams, a melamine-treated foam generated 10 times more HCN than a foam without melamine. The addition of Cu2O to this melamine foam also reduced the HCN generation by 90%. The genetic toxicology research entails the examination of DNA damage that results from the exposure of human cells to various environmental toxicants and gases.

  16. Synthesis, characterization and toxicological evaluation of Cr₂O₃ nanoparticles using Daphnia magna and Aliivibrio fischeri.

    PubMed

    Puerari, Rodrigo Costa; da Costa, Cristina H; Vicentini, Denice S; Fuzinatto, Cristiane F; Melegari, Silvia P; Schmidt, Éder C; Bouzon, Zenilda L; Matias, William G

    2016-06-01

    Chromium III oxide (Cr2O3) nanoparticles (NPs) are used in pigments for ceramics, dyes, paints and cosmetics. However, few studies addressing the toxic potential of these NPs have been reported in the literature. Thus, this research aimed to evaluate the acute and chronic effects of Cr2O3 NPs through acute toxicity tests with Daphnia magna and Aliivibrio fischeri and chronic toxicity tests with Daphnia magna. Cr2O3 NPs were synthesized by the sol-gel method and characterized through TEM, X-Ray diffraction (XRD), zeta potential (ZP) and surface area analysis. In the acute toxicity tests the EC(50,48h) value obtained with D. magna was 6.79 mg L(-1) and for A. fischeri the EC(50,15min) value was 16.10 mg L(-1) and the EC(50,30min) value was 12.91 mg L(-1). Regarding the chronic toxicity tests with D. magna, effects on longevity (OEC=1.00 mg L(-1)), reproduction (OEC=1.00 mg L(-1)) and growth (OEC=0.50 mg L(-1)) were observed. On the SEM and TEM images, ultrastructural alterations in the organelles of exposed organisms were also observed. Thus, toxicological studies with NPs are of great importance in order to reduce the risk of environmental contamination.

  17. Synthesis, characterization and toxicological evaluation of Cr₂O₃ nanoparticles using Daphnia magna and Aliivibrio fischeri.

    PubMed

    Puerari, Rodrigo Costa; da Costa, Cristina H; Vicentini, Denice S; Fuzinatto, Cristiane F; Melegari, Silvia P; Schmidt, Éder C; Bouzon, Zenilda L; Matias, William G

    2016-06-01

    Chromium III oxide (Cr2O3) nanoparticles (NPs) are used in pigments for ceramics, dyes, paints and cosmetics. However, few studies addressing the toxic potential of these NPs have been reported in the literature. Thus, this research aimed to evaluate the acute and chronic effects of Cr2O3 NPs through acute toxicity tests with Daphnia magna and Aliivibrio fischeri and chronic toxicity tests with Daphnia magna. Cr2O3 NPs were synthesized by the sol-gel method and characterized through TEM, X-Ray diffraction (XRD), zeta potential (ZP) and surface area analysis. In the acute toxicity tests the EC(50,48h) value obtained with D. magna was 6.79 mg L(-1) and for A. fischeri the EC(50,15min) value was 16.10 mg L(-1) and the EC(50,30min) value was 12.91 mg L(-1). Regarding the chronic toxicity tests with D. magna, effects on longevity (OEC=1.00 mg L(-1)), reproduction (OEC=1.00 mg L(-1)) and growth (OEC=0.50 mg L(-1)) were observed. On the SEM and TEM images, ultrastructural alterations in the organelles of exposed organisms were also observed. Thus, toxicological studies with NPs are of great importance in order to reduce the risk of environmental contamination. PMID:26890188

  18. Toxicological properties of fenugreek (Trigonella foenum graecum).

    PubMed

    Ouzir, Mounir; El Bairi, Khalid; Amzazi, Saaïd

    2016-10-01

    Fenugreek (Trigonella foenum graecum), used as traditional medicine and natural additive food, has been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several human and animal models. Besides, several medicinal pharmaceutical and nutraceutical properties, fenugreek have toxic effects as well. The aim of this review is discuss the cumulative evidence, which suggests that consumption of fenugreek induced some serious toxicological side effects. In this review, many teratogenic effects of fenugreek, from congenital malformations to death, were reported in human, rodent, rabbit, and chick. Moreover, results obtained in rats, mice and rabbits show a testicular toxicity and anti-fertility effects in male associated with oxidative stress and DNA damage, as well as anti-fertility, antiimplantation and abortifacient activity in females related to saponin compound of fenugreek which suggest that fenugreek is not recommended for use during pregnancy. Indeed, the consumption of fenugreek should be avoided for persons having peanut and chickpeas allergy because of possible cross-reactivity as well as chronic asthma. Accumulating evidence suggest also that fenugreek may have neurodevelopmental, neurobehavioral and neuropathological side effects. It is suggested that future studies would be conducted to identify molecular and cellular mechanisms underlying the fenugreek toxicological properties. PMID:27498339

  19. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    PubMed Central

    Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali

    2016-01-01

    Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress. PMID:27635201

  20. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    PubMed Central

    Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali

    2016-01-01

    Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.

  1. Effect of Dextran 40 and aprotinin on experimental acute pancreatitis.

    PubMed

    Crocket, K V; Reising, J R; Wirman, J A; Gau, N; Joffe, S N

    1984-03-01

    This study examines and compares the prophylactic role of aprotinin and Dextran 40 in acute pancreatitis. Experimental acute pancreatitis was induced in 70 male Wistar rats using the closed-duodenal-loop technique. The rats were randomly divided into four groups; sham operation, untreated acute pancreatitis, and therapy with aprotinin or Dextran 40. Samples of blood and urine were collected at the beginning and at the end of the 24-hr period for measurement of amylase and creatinine which allowed calculation of the amylase-creatinine clearance ratio (ACCR). Mortality in the aprotinin group was the same as the untreated rats (20%). Dextran 40 therapy was associated with a lower mortality rate (6.7%). Light microscopic examination confirmed that the histologic changes of acute pancreatitis were less severe in both the aprotinin- and Dextran 40-treated rats. The ACCR was elevated after Dextran 40 therapy, which was due mainly to high urinary amylase levels. These results suggest that Dextran 40 may have a prophylactic role in acute experimental pancreatitis but again emphasizes the high false-positive rate of the ACCR determination. PMID:6199589

  2. Systemic vascular effects of acute electrical baroreflex stimulation.

    PubMed

    Burgoyne, Steven; Georgakopoulos, Dimitrios; Belenkie, Israel; Tyberg, John V

    2014-07-15

    We intended to determine if acute baroreflex activation therapy (BAT) increases venous capacitance and aortic conductance. BAT is effective in resistant hypertension, but its effect on the systemic vasculature is poorly understood. Left ventricular (LV) and aortic pressures and subdiaphragmatic aortic and caval flows (ultrasonic) were measured in six anesthetized dogs. Changes in abdominal blood volume (Vabdominal) were estimated as the integrated difference in abdominal aortic inflow and caval outflow. An electrode was implanted on the right carotid sinus. Data were measured during control and BAT. Next, sodium nitroprusside (SNP) was infused and BAT was subsequently added. Finally, angiotensin II (ANG II) was infused, and three increased BAT currents were added. We found that BAT decreased mean aortic pressure (PAo) by 22.5 ± 1.3 mmHg (P < 0.001) and increased aortic conductance by 16.2 ± 4.9% (P < 0.01) and Vabdominal at a rate of 2.2 ± 0.6 ml·kg(-1)·min(-1) (P < 0.01). SNP decreased PAo by 17.4 ± 0.7 mmHg (P < 0.001) and increased Vabdominal at a rate of 2.2 ± 0.7 ml·kg(-1)·min(-1) (P < 0.05). During the SNP infusion, BAT decreased PAo further, by 26.0 ± 2.1 mmHg (P < 0.001). ANG II increased PAo by 40.4 ± 3.5 mmHg (P = 0.001). When an increased BAT current was added, PAo decreased to baseline (P < 0.01) while aortic conductance increased from 62.3 ± 5.2% to 80.2 ± 3.3% (P < 0.05) of control. Vabdominal increased at a rate of 1.8 ± 0.9 ml·kg(-1)·min(-1) (P < 0.01), reversing the ANG II effects. In conclusion, BAT increases arterial conductance, decreases PAo, and increases venous capacitance even in the presence of powerful vasoactive drugs. Increasing venous capacitance may be an important effect of BAT in hypertension. PMID:24816258

  3. Public Databases Supporting Computational Toxicology

    EPA Science Inventory

    A major goal of the emerging field of computational toxicology is the development of screening-level models that predict potential toxicity of chemicals from a combination of mechanistic in vitro assay data and chemical structure descriptors. In order to build these models, resea...

  4. RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.

    PubMed

    Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J

    2014-05-27

    The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.

  5. Effect of Acute Surgical Stress on Serum Ghrelin Levels

    PubMed Central

    Kontoravdis, Nikolaos; Vassilikostas, George; Lagoudianakis, Emmanuel; Pappas, Apostolos; Seretis, Charalampos; Panagiotopoulos, Nikolaos; Koronakis, Nikolaos; Chrysikos, John; Karanikas, George; Manouras, Ioannis; Legakis, Ioanis; Voros, Dionysios

    2012-01-01

    Background Ghrelin is an appetite hormone that influences the gastrointestinal function and regulates energy metabolism. Growing evidence also suggests that this hormone plays a central role in immune modulation. Each surgical operation is followed by a series of inflammatory and metabolic changes that constitute the stress response. The aim of our study is to evaluate the effect of stress during different types of abdominal surgery in ghrelin serum levels. Methods An overall of 25 patients were prospectively allocated in two groups based on the type of surgical operation. Group A (n = 10) patients were scheduled to undergo cholecystectomy, whereas Group B (n = 15) patients underwent colectomy. Serum ghrelin concentrations were evaluated in each patient preoperatively, after the induction of general anesthesia and tracheal intubation, one and five hours after the beginning of surgery and the morning of the first and second postoperative day. Results In both groups serum ghrelin concentrations reached their peak level at 24 hr (Group A: 8.4 ± 3.4 ng/mL; Group B: 7.4 ± 1.8 ng/mL) and these values were significantly higher than those in the preoperative period (Group A: 5.0 ±1.5 ng/mL; Group B: 4.8 ± 0.6 ng/mL) (P < 0.05). Forty eight hours after surgery the levels of ghrelin returned to their preoperative status. Patients’ gender, age, ASA score and type of surgical procedure did not influence the serum ghrelin levels. Conclusions Serum ghrelin concentration appears to elevate in response to surgical stress. Future studies are needed to improve comprehension of the mechanisms underlying responses of this hormone to acute surgical stress and to evaluate their possible clinical implications.

  6. Effects of Montelukast in an Experimental Model of Acute Pancreatitis.

    PubMed

    Angı, Serkan; Eken, Hüseyin; Kılıc, Erol; Karaköse, Oktay; Balci, Gürhan; Somuncu, Erkan

    2016-01-01

    BACKGROUND We evaluated the hematological, biochemical, and histopathological effects of Montelukast on pancreatic damage in an experimental acute pancreatitis model created by cerulein in rats before and after the induction of pancreatitis. MATERIAL AND METHODS Forty rats were divided into 4 groups with 10 rats each. The study groups were: the Cerulein (C) group, the Cerulein + early Montelukast (CMe) group, the Cerulein + late Montelukast (CMl) group, and the Control group. The pH, pO2, pCO2, HCO3, leukocyte, hematocrit, pancreatic amylase, and lipase values were measured in the arterial blood samples taken immediately before rats were killed. RESULTS There were statistically significant differences between the C group and the Control group in the values of pancreatic amylase, lipase, blood leukocyte, hematocrit, pH, pO2, pCO2, HCO3, and pancreatic water content, and also in each of the values of edema, inflammation, vacuolization, necrosis, and total histopathological score (P<0.05). When the CMl group and C group were compared, no statistically significant differences were found in any parameter analyzed. When the CMe group was compared with the C group, pancreatic amylase, lipase, pH, PO2, pCO2, HCO3, pancreatic water content, histopathological edema, inflammation, and total histopathological score values were significantly different between the groups (P<0.05). Finally, when the CMe group and the Control group were compared, significant differences were found in all except 2 (leukocyte and pO2) parameters (P<0.05). CONCLUSIONS Leukotriene receptor antagonists used in the late phases of pancreatitis might not result in any benefit; however, when they are given in the early phases or prophylactically, they may decrease pancreatic damage. PMID:27479458

  7. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  8. Acute effects of smoking on QT dispersion in healthy males

    PubMed Central

    Akbarzadeh, Mohammad Ali; Yazdani, Shahrooz; Ghaidari, Mohamad Esmail; Asadpour-Piranfar, Mohammad; Bahrololoumi-Bafruee, Negar; Golabchi, Allahyar; Azhari, Amirhossein

    2014-01-01

    BACKGROUND Cigarette smoking increases the risk of ventricular fibrillation and sudden cardiac death (SCD). QT dispersion (QTD) is an important predictor of cardiac arrhythmia. The aim of this study was to assess the acute effect of smoking a single standard cigarette containing 1.7 mg nicotine on QT interval and QTD in healthy smokers and nonsmokers. METHODS The study sample population consisted of 40 healthy male hospital staff, including 20 smokers and 20 nonsmokers. They were asked to refrain from smoking at least 6 h before attending the study. A 12-lead surface electrocardiogram (ECG), recorded at paper speed of 50 mm/s, was obtained from all participants before and 10 min after smoking of a single complete cigarette. QT interval, corrected QT interval, QTD, and corrected QT dispersion (QTcD) were measured before and after smoking. RESULTS Smokers and nonsmokers did not have any significant differences in heart rate (HR) (before smoking = 67.35 ± 5.14 vs. 67.70 ± 5.07, after smoking = 76.70 ± 6.50 vs. 76.85 ± 6.50, respectively), QTD (before smoking = 37.75 ± 7.16 vs. 39.15 ± 6.55, after smoking = 44.75 ± 11.97 vs. 45.50 ± 9.58, respectively), and QTcD (before smoking = 39.85 ± 7.40 vs. 41.55 ± 6.57, after smoking = 50.70 ± 14.31 vs. 51.50 ± 11.71, respectively). However, after smoking a single cigarette, HR, mean QTD, and QTcD significantly increased (all had P value <0.001) in comparison to the measures before smoking. CONCLUSION Smoking of a single complete cigarette in both smokers and nonsmokers results in significant QTD increase, which can cause arrhythmia and SCD. PMID:25161676

  9. Acute exposure to acid fog. Effects on mucociliary clearance

    SciTech Connect

    Laube, B.L.; Bowes, S.M. III; Links, J.M.; Thomas, K.K.; Frank, R. )

    1993-05-01

    Submicrometric sulfuric acid (H2SO4) aerosol can affect mucociliary clearance without eliciting irritative symptoms or changes in pulmonary function. The effect of larger fog droplets containing H2SO4 on mucociliary clearance is unknown. We quantified mucociliary clearance from the trachea (n = 4) and small airways (n = 7) of young healthy male adults after an acute exposure to H2SO4 fog (MMAD = 10.3 microns; pH = 2.0; liquid water content = 481 +/- 65 mg/m3; osmolarity = 30 mOsm). Acid fog (AF) or saline fog (SF) (10.9 microns; 492 +/- 116 mg/m3; 30 mOsm) was administered for 40 min of unencumbered breathing (no mouth-piece) at rest and for 20 min of exercise sufficient to produce oronasal breathing. Fog exposures were followed by a methacholine (MCh) challenge (a measure of airway reactivity) or inhalation of technetium-99M radioaerosol (MMAD = 3.4 microns) on 2 study days each. Changes in symptoms and forced ventilatory function were also assessed. Clearance was quantified from computer-assisted analyses of gamma camera images of the lower respiratory tract in terms of %removal/min of the radiolabel from the trachea 25 min after inhalation and from the outer zone of the right lung after 1.9 to 3 h. Symptoms, forced ventilatory function, and MCh response were unaffected by either fog. Tracheal clearance was more rapid in four of four subjects after AF (0.83 +/- 1.58% removal/min) compared with that after SF (-0.54 +/- 0.85% removal/min). Outer zone clearance was more rapid in six of seven subjects after AF (0.22 +/- 0.15% removal/min) compared with that after SF (0.01 +/- 0.09% removal/min).

  10. Effects of Montelukast in an Experimental Model of Acute Pancreatitis

    PubMed Central

    Angı, Serkan; Eken, Hüseyin; Kılıç, Erol; Karaköse, Oktay; Balci, Gürhan; Somuncu, Erkan

    2016-01-01

    Background We evaluated the hematological, biochemical, and histopathological effects of Montelukast on pancreatic damage in an experimental acute pancreatitis model created by cerulein in rats before and after the induction of pancreatitis. Materials/Methods Forty rats were divided into 4 groups with 10 rats each. The study groups were: the Cerulein (C) group, the Cerulein + early Montelukast (CMe) group, the Cerulein + late Montelukast (CMl) group, and the Control group. The pH, pO2, pCO2, HCO3, leukocyte, hematocrit, pancreatic amylase, and lipase values were measured in the arterial blood samples taken immediately before rats were killed. Results There were statistically significant differences between the C group and the Control group in the values of pancreatic amylase, lipase, blood leukocyte, hematocrit, pH, pO2, pCO2, HCO3, and pancreatic water content, and also in each of the values of edema, inflammation, vacuolization, necrosis, and total histopathological score (P<0.05). When the CMl group and C group were compared, no statistically significant differences were found in any parameter analyzed. When the CMe group was compared with the C group, pancreatic amylase, lipase, pH, PO2, pCO2, HCO3, pancreatic water content, histopathological edema, inflammation, and total histopathological score values were significantly different between the groups (P<0.05). Finally, when the CMe group and the Control group were compared, significant differences were found in all except 2 (leukocyte and pO2) parameters (P<0.05). Conclusions Leukotriene receptor antagonists used in the late phases of pancreatitis might not result in any benefit; however, when they are given in the early phases or prophylactically, they may decrease pancreatic damage. PMID:27479458

  11. Predicting the acute behavioral effects in rats inhaling toluene (or up to 24 hrs: Inhaled vs. internal dose metrics.

    EPA Science Inventory

    The acute toxicity oftoluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) ofexposure, and guidelines for acute exposures have traditionally used ext relationships to extrapolate protective and/or effective concentrations across durat...

  12. Evaluation of toxicological properties and photodynamic activity of Photolon ointment: an experimental study

    NASA Astrophysics Data System (ADS)

    Shliakhtsin, Siarhei V.; Trukhachova, Tatsiana V.; Istomin, Yuriy P.; Dunetz, Ludmila N.; Kuvshinov, Andrey V.; Naumovich, Semen A.

    2009-06-01

    The purpose of the present study was to evaluate toxicological properties and photodynamic activity of a new ready form of the photosensitizer Photolon (Fotolon) - an ointment for topical use. The data obtained show the use of topicaly applied photosensitizer provides sufficient penetration and accumulation of the active compound in tumor tissue as well as in affected periodontal tissues for the effective PDT. There are several advantages of PDT with topical application of the photosensitizer such as absence of systemic toxic and photosensitive reactions, relatively low cost of the treatment and etc. We have shown that PDT of affected periodontal tissues with local application of Photolon/Fotolon ointment provides an ability of local destruction of microbial cell, located as on the gum surface as in the spatium intercellulare what is extremely important for successful treatment of acute and chronic periodontitis.

  13. Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism.

    PubMed

    Stahl, Simone H; Yates, James W; Nicholls, Andrew W; Kenna, J Gerry; Coen, Muireann; Ortega, Fernando; Nicholson, Jeremy K; Wilson, Ian D

    2015-08-01

    One aim of systems toxicology is to deliver mechanistic, mathematically rigorous, models integrating biochemical and pharmacological processes that result in toxicity to enhance the assessment of the risk posed to humans by drugs and other xenobiotics. The benefits of such 'in silico' models would be in enabling the rapid and robust prediction of the effects of compounds over a range of exposures, improving in vitro-in vivo correlations and the translation from preclinical species to humans. Systems toxicology models of organ toxicities that result in high attrition rates during drug discovery and development, or post-marketing withdrawals (e.g., drug-induced liver injury (DILI)) should facilitate the discovery of safe new drugs. Here, systems toxicology as applied to the effects of paracetamol (acetaminophen, N-acetyl-para-aminophenol (APAP)) is used to exemplify the potential of the approach. PMID:26464084

  14. Acute Effects of Fine Particulate Air Pollution on ST Segment Height: A Longitudinal Study

    EPA Science Inventory

    Background: The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. Methods: We investigate the acute effects and the time cours...

  15. Behavioral effects of acute and long-term administration of catnip (Nepeta cataria) in mice.

    PubMed

    Massoco, C O; Silva, M R; Gorniak, S L; Spinosa, M S; Bernardi, M M

    1995-12-01

    Catnip or catmint (Nepeta cataria) is a plant used extensively to treat human diseases and in toys for pets. We investigated the effects of acute and long-term administration of the plant on some behaviors of mice. The plant was fed as 10% of the normal diet for 2 h/d for 1 or 7 d. Acute and long-term dosing increased both rearing and locomotion frequencies observed in an open field. Acute exposure to catnip increased stereotyped behavior and susceptibility to seizures, did not interfere with haloperidol-induced catalepsy, and decreased sleeping time after sodium pentobarbital administration. Long-term exposure induced tolerance to stereotypic behavior, catalepsy and sleeping time, and increased the susceptibility to seizures induced by picrotoxin and strychnine. An amphetamine-like effect of catnip was suggested to explain the acute effects, while dispositional and functional adaptative changes were considered involved with the long-term effects.

  16. Implications of gender differences for human health risk assessment and toxicology

    EPA Science Inventory

    This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exp...

  17. Genetic toxicology of lysergic acid diethylamide (LSD-25).

    PubMed

    Cohen, M M; Shiloh, Y

    The acute and the chronic psychotomimetic potentials of the hallucinogen lysergic acid diethylamide (LSD-25) have been recognized for almost 40 years. That additional types of the biological effects should have come under scrutiny was directly attributable to widespread use and abuse of this drug on a world-wide basis. Although "genetic toxicology" encompasses a broad spectrum of disciplines, including many areas of highly specialized research, perhaps the most germane, and those on which this review has concentrated, are Clastogenicity, Mutagenicity, Teratogenicity and Oncogenicity. Based on our current understanding and interpretation of the available data, the genetic toxicology of LSD provides an excellent example of Newton's "third law of motion", e.g., to every force there is an equal and opposite reaction force. From the published material it is impossible to draw clear cut conclusions regarding any of the above "problem areas" in spite of the considerable scientific effort invested. Most of the in vitro studies performed on the clastogenicity of LSD indicate either suppression of mitosis or enhanced chromosome damage. However, extrapolation of such results to the in vivo situation is very difficult. With regard to in vivo human use of the drug, no concensus is attainable as to chromosome breakage and the inconsistencies within and between studies remain inexplicable. However, several of the "controlled" investigations assessing the in vivo effect of chemically pure LSD suggest a transient increase in lymphocyte chromosome breakage. On the other hand, the results of cytogenetic studies on experimental animals are contradictory. Although human studies are nonexistent, in those experimental organisms tested, using accepted techniques, LSD proved to be, at best, a weak mutagen, if mutagenic at all. Teratogenicity studies in animals are confusing due to the multitude of organisms and plethora of discriminant parameters studied. However, with regard to man there

  18. Genetic toxicology of lysergic acid diethylamide (LSD-25).

    PubMed

    Cohen, M M; Shiloh, Y

    The acute and the chronic psychotomimetic potentials of the hallucinogen lysergic acid diethylamide (LSD-25) have been recognized for almost 40 years. That additional types of the biological effects should have come under scrutiny was directly attributable to widespread use and abuse of this drug on a world-wide basis. Although "genetic toxicology" encompasses a broad spectrum of disciplines, including many areas of highly specialized research, perhaps the most germane, and those on which this review has concentrated, are Clastogenicity, Mutagenicity, Teratogenicity and Oncogenicity. Based on our current understanding and interpretation of the available data, the genetic toxicology of LSD provides an excellent example of Newton's "third law of motion", e.g., to every force there is an equal and opposite reaction force. From the published material it is impossible to draw clear cut conclusions regarding any of the above "problem areas" in spite of the considerable scientific effort invested. Most of the in vitro studies performed on the clastogenicity of LSD indicate either suppression of mitosis or enhanced chromosome damage. However, extrapolation of such results to the in vivo situation is very difficult. With regard to in vivo human use of the drug, no concensus is attainable as to chromosome breakage and the inconsistencies within and between studies remain inexplicable. However, several of the "controlled" investigations assessing the in vivo effect of chemically pure LSD suggest a transient increase in lymphocyte chromosome breakage. On the other hand, the results of cytogenetic studies on experimental animals are contradictory. Although human studies are nonexistent, in those experimental organisms tested, using accepted techniques, LSD proved to be, at best, a weak mutagen, if mutagenic at all. Teratogenicity studies in animals are confusing due to the multitude of organisms and plethora of discriminant parameters studied. However, with regard to man there

  19. Computational chemistry, systems biology and toxicology. Harnessing the chemistry of life: revolutionizing toxicology. a commentary.

    PubMed

    Kimber, Ian; Humphris, Colin; Westmoreland, Carl; Alepee, Nathalie; Negro, Gianni Dal; Manou, Irene

    2011-04-01

    There is a continuing interest in, and increasing imperatives for, the development of alternative methods for toxicological evaluations that do not require the use of animals. Although a significant investment has resulted in some achievements, progress has been patchy and there remain many challenges. Among the most significant hurdles is developing non-animal methods that would permit assessment of the potential for a chemical or drug to cause adverse health effects following repeated systemic exposure. Developing approaches to address this challenge has been one of the objectives of the European Partnership for Alternative Approaches to Animal Testing (EPAA). The EPAA is a unique partnership between the European Commission and industry that has interests in all aspects of reducing, refining and replacing the use of animals (the '3Rs'). One possible strategy that emerged from a broad scientific debate sponsored by the EPAA was the opportunity for developing entirely new paradigms for toxicity testing based upon harnessing the increasing power of computational chemistry in combination with advanced systems biology. This brief commentary summarizes a workshop organized by the EPAA in 2010, that had the ambitious title of 'Harnessing the Chemistry of Life: Revolutionizing Toxicology'. At that workshop international experts in chemistry, systems biology and toxicology sought to map out how best developments in these sciences could be exploited to design new strategies for toxicity testing using adverse effects in the liver as an initial focus of attention. Here we describe the workshop design and outputs, the primary purpose being to stimulate debate about the need to align different areas of science with toxicology if new and truly innovative approaches to toxicity testing are to be developed.

  20. Effects of Acute Stress on Decision Making under Ambiguous and Risky Conditions in Healthy Young Men.

    PubMed

    Cano-López, Irene; Cano-López, Beatriz; Hidalgo, Vanesa; González-Bono, Esperanza

    2016-01-01

    Acute stress and decision making (DM) interact in life - although little is known about the role of ambiguity and risk in this interaction. The aim of this study is to clarify the effect of acute stress on DM under various conditions. Thirty-one young healthy men were randomly distributed into two groups: experimental and control. DM processes were evaluated before and after an experimental session. For the experimental group, the session consisted of an acute stress battery; and the protocol was similar for the control group but the instructions were designed to minimize acute stress. Cardiovascular variables were continuously recorded 30 minutes before the DM tasks and during the experimental session. Cortisol, glucose, mood responses, and personality factors were also assessed. Acute stress was found to enhance disadvantageous decisions under ambiguous conditions (F(1, 29) = 4.16, p = .05, η2 p = .13), and this was mainly explained by the stress induced cortisol response (26.1% of variance, F(1, 30) = 11.59, p = .002). While there were no significant effects under risky conditions, inhibition responses differed between groups (F(1, 29) = 4.21, p = .05, η2 p = .13) and these differences were explained by cardiovascular and psychological responses (39.1% of variance, F(3, 30) = 7.42, p < .001). Results suggest that DM tasks could compete with cognitive resources after acute stress and could have implications for intervention in acute stress effects on DM in contexts such as addiction or eating disorders. PMID:27644414