Evaluation of a Hungarian acaricide original molecule based on its environmental toxicological studies.

PubMed

Szamosi, D; Oláh, B; Hirka, G; Pap, L; Gáty, S

2000-07-01

The results of the environmental toxicological investigations and their results of a new hungarian acaricide molecule (SZI-121) developed by the CHINOIN were summarized. The toxicological effects of the test item on different ecotoxicological test systems were investigated in the following tests: Bacterium, alga, and plant growth inhibition tests, acute immobilization and 21 days reproduction tests on Daphnia magna, acute fish test, closed bottle test, mobility, aerob degradation and adsorption/desorption tests on three different soils. No toxic effect was found in the bacterium, alga, plant growth inhibition and acute fish tests in the highest concentrations used. In the Daphnia immobilization test 0.14 mg/l LC50 value was established in the concentration range of 0.0128-40 mg/l applied. The test item showed similar characteristics as the reference item during the mobility test in soils, the adsorption/desorption study and the degradation investigations. In order to determine the environmental degradation rate further degradation investigations, as well as the nitrogen mineralization test and the model of concentration change in natural waters were performed.

Aviation combustion toxicology: an overview.

PubMed

Chaturvedi, Arvind K

2010-01-01

Aviation combustion toxicology is a subspecialty of the field of aerospace toxicology, which is composed of aerospace and toxicology. The term aerospace, that is, the environment extending above and beyond the surface of the Earth, is also used to represent the combined fields of aeronautics and astronautics. Aviation is another term interchangeably used with aerospace and aeronautics and is explained as the science and art of operating powered aircraft. Toxicology deals with the adverse effects of substances on living organisms. Although toxicology borrows knowledge from biology, chemistry, immunology, pathology, physiology, and public health, the most closely related field to toxicology is pharmacology. Economic toxicology, environmental toxicology, and forensic toxicology, including combustion toxicology, are the three main branches of toxicology. In this overview, a literature search for the period of 1960-2007 was performed and information related to aviation combustion toxicology collected. The overview included introduction; combustion, fire, and smoke; smoke gas toxicity; aircraft material testing; fire gases and their interactive effects; result interpretation; carboxyhemoglobin and blood cyanide ion levels; pyrolytic products of aircraft engine oils, fluids, and lubricants; and references. This review is anticipated to be an informative resource for aviation combustion toxicology and fire-related casualties.

Measuring drug absorption improves interpretation of behavioral responses in a larval zebrafish locomotor assay for predicting seizure liability.

PubMed

Cassar, Steven; Breidenbach, Laura; Olson, Amanda; Huang, Xin; Britton, Heather; Woody, Clarissa; Sancheti, Pankajkumar; Stolarik, DeAnne; Wicke, Karsten; Hempel, Katja; LeRoy, Bruce

2017-11-01

Unanticipated effects on the central nervous system are a concern during new drug development. A larval zebrafish locomotor assay can reveal seizure liability of experimental molecules before testing in mammals. Relative absorption of compounds by larvae is lacking in prior reports of such assays; having those data may be valuable for interpreting seizure liability assay performance. Twenty-eight reference drugs were tested at multiple dose levels in fish water and analyzed by a blinded investigator. Responses of larval zebrafish were quantified during a 30min dosing period. Predictive metrics were calculated by comparing fish activity to mammalian seizure liability for each drug. Drug level analysis was performed to calculate concentrations in dose solutions and larvae. Fifteen drug candidates with neuronal targets, some having preclinical convulsion findings in mammals, were tested similarly. The assay has good predictive value of established mammalian responses for reference drugs. Analysis of drug absorption by larval fish revealed a positive correlation between hyperactive behavior and pro-convulsive drug absorption. False negative results were associated with significantly lower compound absorption compared to true negative, or true positive results. The predictive value for preclinical toxicology findings was inferior to that suggested by reference drugs. Disproportionately low exposures in larvae giving false negative results demonstrate that drug exposure analysis can help interpret results. Due to the rigorous testing commonly performed in preclinical toxicology, predicting convulsions in those studies may be more difficult than predicting effects from marketed drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of Toxicity Data for Munition Compounds to Support Toxicity Reference Value Derivations for Wildlife

DTIC Science & Technology

2010-06-01

or IVOS) Sperm Analyzer, Version 12.1 Final Report, Toxicology Report No. 87-XE-06ED-05, January 2005−January 2010 7 (Hamilton-Thorne Research...vas deferens were not different across treatments (F = 1.46; df = 5, 48; p = 0.221, data not shown). Sperm counts calculated as number per vas...in species with simple gastrointestinal structures and short retention times; whereas, species with expanded gut physiologies and retention times

IRIS Toxicological Review of Chloroprene (Peer Review Plan) ...

EPA Pesticide Factsheets

Chloroprene (C4H5Cl; 2-chloro-1,3-butadiene, CASRN 126-99-8) is a volatile, flammable liquid monomer used exclusively in the manufacture of neoprene (polychloroprene) elastomer which is used to make diverse products such as belts, hoses, gloves, wire coatings, and tubing. Chloroprene has a high vapor pressure, readily evaporates from water and solid surfaces, and readily oxidizes and form dimers and other oxygenated species in the absence of stabilizers (e.g., phenothiazine). When released to soil it may leach into groundwater, but breakdown via hydrolysis is not likely. Absorption into the body is possible through the lungs, gastrointestinal tract, or skin, and widespread distribution is evidenced by many target sites exhibiting effects. EPA has not developed an assessment of the potential for human health effects from exposure to chloroprene. Initial stages of development for this assessment are underway. The assessment is likely to include an oral reference value (RfD), an inhalation reference value (RfC), and a carcinogenicity assessment. Chloroprene will be entered into IRIS. IRIS is the Agency-approved source of toxicological and risk information accessible to the public, EPA regional offices, state governments and EPA regulatory program offices. This evaluation supports the Office of Air Quality Planning and Standards-Office of Air and Radiation in assessing the hazardous effects of chemicals that are listed as the greatest threat to the public

Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC.

PubMed

Tarazona, Jose V; Court-Marques, Daniele; Tiramani, Manuela; Reich, Hermine; Pfeil, Rudolf; Istace, Frederique; Crivellente, Federica

2017-08-01

Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.

IRIS Toxicological Review of Vanadium Pentoxide ...

EPA Pesticide Factsheets

On September 30, 2011, the draft Toxicological Review of Vanadium Pentoxide and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process (May 2009), introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Vanadium Pentoxide and the charge to external peer reviewers are posted on this site. EPA is reassessing its IRIS toxicological review of vanadium pentoxide (CASRN 1314-62-1). This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This assessment is intended to provide human health data to support agency regulatory decisions.

IRIS Toxicological Review of Beryllium and Compounds (2008 ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database. An IRIS Toxicological Review of Beryllium and Compounds was published in 1988 and reassessed in 1998. The current draft (2007) only focuses on the cancer assessment and does not re-evaluate posted reference doses or reference concentrations.

Toxicology in Addiction Medicine.

PubMed

Schwarz, Daniel A; George, M P; Bluth, Martin H

2016-12-01

Toxicology testing in addiction medicine varies across the spectrum, yet remains a powerful tool in monitoring addictive patients. There are many reference laboratories offering toxicology testing, and physicians should have some understanding of laboratory, methodology, testing portfolio, and customer support structure to aid them in selecting the best toxicology laboratory for their patients. Consultation with a clinical pathologist/toxicologist in conjunction with the consideration of monitoring large numbers of illicit and psychoactive drugs in the addictive patient may provide important clinical information for their treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

Trichloroacetic acid is a crystalline solid with sharp, pungent odor. It is used as a soil sterilizer; and as a laboratory intermediate or reagent in the synthesis of a variety of medicinal products and organic chemicals. Trichloroacetic acid is also used industrially as an etching and pickling agent for the surface treatment of metals and as a solvent in the plastics industry. Trichloroacetic acid can be formed as a combustion byproduct of organic compounds in the presence of chlorine. It is also formed as a disinfection byproduct during water chlorination. The existing IRIS entry was added to the IRIS data base between 1994 and 1996. No RfD was developed. The IRIS program is updating the IRIS assessment for Trichloroacetic Acid. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for Trichloroacetic Acid will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference value for noncancer effects of Trichloroacetic Acid (RfD) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review and external scientific peer review. The final products will constitute the Agency's opinion on the

An Indexing Coverage Study of Toxicological Literature

ERIC Educational Resources Information Center

Montgomery, Ruth Reinke

1973-01-01

The goal of this study was an appraisal of indexing coverage for the interdisciplinary field of toxicology. Information of research significance was limited to primary literature, defined as published documents containing original data from experimental work or case studies. (6 references) (Author/NH)

Health related guide values for drinking-water since 1993 as guidance to assess presence of new analytes in drinking-water.

PubMed

Dieter, Hermann H

2014-03-01

Regulatory toxicologists, when going into assessment of a new analyte in drinking-water, very often miss the occasion to revert to scientifically consensual virtually safe lifetime exposure reference doses and corresponding health-related guide values (HRGV) for drinking-water, be those derived either to avoid concern over "threshold effects" or concern over exceedance of an unacceptable non-threshold cancer risk level. They then need a more restrictive precautionary yet science-compatible approach to directly avoid concern over the presence (measured concentration) of a new analyte in drinking-water. Therefore, the German Environment Agency (UBA, Umweltbundesamt) decided in 2003 to extrapolate international toxicological expertise collected since 1993 from assessing "old" analytes in drinking-water on new ones in form of five HRIV=health related indication values. They indicate the reasonable lowest maximal concentration from which on tiered or stepwise human toxicological evaluation of a new analyte might be necessary and meaningful. Their regulatory-toxicological function is that of placeholders as long as a possibly higher scientific HRGV or a surrogate value based on a threshold of toxicological concern (TTC) was not broadly agreed by science. The five-step HRIV scale between 0.01 and 3.0 μg/l combines international toxicological experience gained from "old" analytes since 1993 with the concepts of safety factors (SF(D)) to assess database deficiency and science-related extrapolation factors (EF) to extrapolate experimental data on humans. Each HRIV is valid and safe for a 2 l/day drinking-water exposure scenario either counting for 10% relative source contribution (compounds with threshold effects) or for a lifetime non-threshold cancer risk of up to 10(-6) and is the higher the more positive information exists regarding possible effects at critical toxic endpoints and for length of possible exposure. Past (historical) and present evaluations of "old" analytes were available in form of hundreds of HRGVs to count in 2 liters per day and person for 10% RSC or a 10(-6) non-threshold risk. These HRGVs were calculated by the present author either from ADI-, TDI- or RfD-values derived since 1993 by six large health authorities or they were identified directly at their websites or in the literature, always looking for confirmed or assumed worldwide relevance for drinking-water (resources). 36 of these up to 200 "old" analytes were ascribed since 1993 at least once an HRGV at or below 1 μg/l for (confirmed or provisionally assumed) "high" or "very high" threshold chronic toxicity. None but one of the corresponding 113 scientific HRGVs fell distinctly short of 0.3 μg/l. Only 14 carcinogens turned out as being relevant for drinking-water due to confirmed occurrence and coincident toxicological significance there. 13 of these exhibited a structural alert for genotoxicity. Ten of these 13 were "high-potency" genotoxic carcinogens with presently calculated non-threshold 10(-6) risk minimal HRGVs between 0.06 μg/l and 0.005 μg/l (9 compounds) or possibly down to 0.0007 μg/l (1 compound). This motivated UBA to propose a precautionary range between a minimal HRIV0=0.01 and a HRIV1=0.1 μg/l to assess new analytes bearing a structural alert for genotoxicity. The HRGVs for the remaining three (from 13) carcinogens with alerts for genotoxicity were at best similar for both genotoxic and non-genotoxic effects and higher or equal to 0.3 μg/l. Therefore, a minimal HRIV of 0.01 μg/l (HRIV0) or even 0.1 μg/l (HRIV1) would have appeared too low for assessing the presence in drinking-water of new analytes with no other human toxicity data than proven absence of both genotoxicity and of structural alerts for such. Instead, UBA proposes to provisionally assess such compounds by its next higher precautionary of HRIV3=0.3 μg/l. Any value once set is open for falsification upwards to either 1.0 μg/l (HRIV4) or 3.0 μg/l (HRIV5) or even for being replaced by an HRGV>3.0 μg/l if pertinent high toxicity effect potentials different from genotoxicity are similarly ruled out by either mechanistic and TTC-based arguments or a tiered experimental (in vitro and/or in vivo) approach. Regulatory-toxicological expertise gained since 1993 with "old" analytes in drinking-water (resources) and its extrapolation by analogy on new analytes with patchy human toxicological database allows for provisional assessment of their presence in drinking-water in form of five precautionary HRIVs. Selecting a HRIV, instead referring to a TTC or a virtually safe reference dose, just asks an expert judgment on the degree of formal completeness and informational potential of a new analyte's human toxicity database. Exceedance of a HRIV indicates need for supplementary toxicological data to improve assessment, their nature and comprehensiveness depending on degree and expected length of exceedance. The regulatory function of a HRIV is that of a placeholder for a possibly higher TTC-based surrogate HRGVTTC or a highest possible science-based HRGV. Copyright © 2013 Elsevier GmbH. All rights reserved.

Essential and toxic elements in commercial baby food on the Spanish and Serbian market.

PubMed

Škrbić, Biljana; Živančev, Jelena; Jovanović, Grigorije; Farre, Marinella

2017-03-01

About 10 heavy elements were determined in 90 samples of baby food collected from Spanish and Serbian market. The results indicated that iron, manganese and copper were most frequently detected. Tin was the predominant toxic element in both Spanish and Serbian samples, with occurrence frequencies of 12.5% and 10.0%, respectively. Element intake for Spanish and Serbian infants were estimated and compared with the recommended reference values, for the majority of elements being lower than one. However, iron and manganese intake through consumption of infant/follow-on formulas were assessed to be higher than the respective daily intakes. Particular attention should be paid to the exposure of infants who consume porridges made of vegetables and fish or chicken, because they may ingest certain elements, particularly arsenic and lead, at levels that exceed the reference toxicological values. Principal component analysis (PCA) was applied to classify and distinguish the different types of baby food.

Fragment-based approach to calculate hydrophobicity of anionic and nonionic surfactants derived from chromatographic retention on a C18 stationary phase.

PubMed

Hammer, Jort; Haftka, Joris J-H; Scherpenisse, Peter; Hermens, Joop L M; de Voogt, Pim W P

2017-02-01

To predict the fate and potential effects of organic contaminants, information about their hydrophobicity is required. However, common parameters to describe the hydrophobicity of organic compounds (e.g., octanol-water partition constant [K OW ]) proved to be inadequate for ionic and nonionic surfactants because of their surface-active properties. As an alternative approach to determine their hydrophobicity, the aim of the present study was therefore to measure the retention of a wide range of surfactants on a C 18 stationary phase. Capacity factors in pure water (k' 0 ) increased linearly with increasing number of carbon atoms in the surfactant structure. Fragment contribution values were determined for each structural unit with multilinear regression, and the results were consistent with the expected influence of these fragments on the hydrophobicity of surfactants. Capacity factors of reference compounds and log K OW values from the literature were used to estimate log K OW values for surfactants (log KOWHPLC). These log KOWHPLC values were also compared to log K OW values calculated with 4 computational programs: KOWWIN, Marvin calculator, SPARC, and COSMOThermX. In conclusion, capacity factors from a C 18 stationary phase are found to better reflect hydrophobicity of surfactants than their K OW values. Environ Toxicol Chem 2017;36:329-336. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

An assessment of health risks associated with arsenic exposure via consumption of homegrown vegetables near contaminated glassworks sites.

PubMed

Uddh-Söderberg, Terese E; Gunnarsson, Sara J; Hogmalm, K Johan; Lindegård, M I Boel G; Augustsson, Anna L M

2015-12-01

The health risk posed by arsenic in vegetables grown in private gardens near 22 contaminated glassworks sites was investigated in this study. Firstly, vegetable (lettuce and potato) and soil samples were collected and arsenic concentrations measured to characterize the arsenic uptake in the selected crops. Secondly, a probabilistic exposure assessment was conducted to estimate the average daily intake (ADIveg), which was then evaluated against toxicological reference values by the calculation of hazard quotients (HQs) and cancer risks (CRs). The results show that elevated arsenic concentrations in residential garden soils are mirrored by elevated concentrations in vegetables, and that consumption of these vegetables alone may result in an unacceptable cancer risk; the calculated reasonable maximum exposure, for example, corresponded to a cancer incidence 20 times higher than the stated tolerance limit. However, the characterization of risk depends to a great extent on which toxicological reference value is used for comparison, as well as how the exposure is determined. Based on the assumptions made in the present study, the threshold levels for chronic non-carcinogenic or acute effects were not exceeded, but the cancer risks indicated highlight the need for further exposure studies, as dietary intake involves more than just homegrown vegetables and total exposure is a function of more than just one exposure pathway. In addition, glassworks sites--and contaminated sites in general--contain multiple contaminants, affecting the final and total risk. Copyright © 2015. Published by Elsevier B.V.

Estimating acute and chronic exposure of children and adults to chlorpyrifos in fruit and vegetables based on the new, lower toxicology data.

PubMed

Mojsak, Patrycja; Łozowicka, Bożena; Kaczyński, Piotr

2018-05-09

This paper presents, for the first time, results for chlorpyrifos (CHLP) in Polish fruits and vegetables over the course of a long period of research, 2007-2016, with toxicological aspects. The challenge of this study was to re-evaluate the impact of chlorpyrifos residues in fruit and vegetables on health risk assessed via acute and chronic exposure based on old and new, lower, established values of: Average Daily Intakes (ADIs)/Acute Reference Doses (ARfDs) and Maximum Residue Levels (MRLs). A total of 3 530 samples were collected, and CHLP in the range of 0.005-1.514 mg/kg was present in 10.2% of all samples. The MRL was exceeded in 0.7% of all samples (MRL established in 2009-2015), and recalculation yielded a much greater number of violations for the new MRL (2016), which exceeded 2.9% of all samples. Acute exposure to CHLP calculated according to the old, higher toxicological data (0.10 mg/kg bw/day), does not exceed 14% of its respective ARfDs for adults and both groups of children, but when calculated for incidental cases according to the current value (ARfD 0.005 mg/kg bw) for infants and toddlers, was above 100% of its respective ARfDs in: white cabbage (263.65% and 108.24%), broccoli (216.80% and 194.72%) and apples (153.20% and 167.70%). The chronic exposure calculated for both newly established ADI values (0.001 mg/kg bw/day and 0.100 mg/kg bw/day) appears to be relatively low for adults and children. Copyright © 2018 Elsevier Inc. All rights reserved.

Estimation of the upper bound of predictive performance for alternative models that use in vivo reference data (OpenTox USA 2017)

EPA Science Inventory

The number of chemicals with limited toxicological information for chemical safety decision-making has accelerated alternative model development, which often are evaluated via referencing animal toxicology studies. In vivo studies are generally considered the standard for hazard ...

Reduced toxicological activity of cigarette smoke by the addition of ammonia magnesium phosphate to the paper of an electrically heated cigarette: subchronic inhalation toxicology.

PubMed

Moennikes, O; Vanscheeuwijck, P M; Friedrichs, B; Anskeit, E; Patskan, G J

2008-05-01

Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields.

[Health risks from pest control products].

PubMed

Pieper, C; Holthenrich, D; Schneider, H

2014-05-01

According to European biocide legislation, pest control products require assessment and authorization by the responsible national or European authorities. Biocidal products can only be authorized if they have no unacceptable effects on human health. The health risk assessment performed for authorization comprises (a) the derivation of reference values for the active substances and substances of concern contained in the biocidal product and (b) an exposure assessment. These parameters are required for risk characterization. No unacceptable health risks are expected if the determined exposure is less than the relevant reference value. In addition, the toxicological information is used for classification of the biocidal product. The assessment may, where necessary, result in specific conditions for use or other restrictions aimed at minimizing risk. The risk to human health from pest control products is mainly based on the toxicological properties of their active substances. Commonly, the coformulants used in pest control products are of less concern than the active substances (e.g., food ingredients and animal feed products). For example, most rodenticides belong to the group of anticoagulants, which are also effective in humans. Regarding intoxications through insecticides, the group of pyrethroids is of particular importance. Fumigants containing metal phosphides, hydrogen cyanide, or sulfuryl difluoride are particularly toxic. This toxicity is linked to the high acute inhalation toxicity of the gaseous active substances themselves or, in the case of phosphides, of the released gas phosphane. The aim of health risk assessment for the authorization of biocidal products is to ensure their safe application for users and all other persons involved, assuming an adequate and label-compliant use.

Evidence-Based Toxicology.

PubMed

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

IRIS Toxicological Review of Tetrachloroethylene ...

EPA Pesticide Factsheets

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of tetrachloroethylene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appropriately in derivation of the toxicological characterization and dose-response assessments. This draft health assessment addresses both non-cancer and cancer human health effects that may result from chronic exposure to tetrachloroethylene (also called Perchloroethylene or Perc) . This is an update of an existing assessment posted on IRIS in 1988. This draft Toxicological Review includes a chronic Reference Concentration (RfC) and carcinogenicity assessment, which are not currently available on IRIS, as well as an update of the 1988 IRIS Reference Dose (RfD). Tetrachloroethylene is a chemical solvent that is widely used for dry cleaning of fabrics, metal degreasing, and in making some consumer products and other chemicals.

Clinical chemistry and hematology values in a Caribbean population of African green monkeys.

PubMed

Liddie, Shervin; Goody, Robin J; Valles, Rodrigo; Lawrence, Matthew S

2010-12-01

Hematology and clinical chemistry (HCC) reference values are critical in veterinary practice and in vivo pre-clinical research, enabling detection of health abnormalities, response to therapeutic intervention or adverse toxicological effects, as well as monitoring of clinical management. In this report, reference ranges for 46 HCC parameters were characterized in 331 wild-caught and colony-bred African green monkeys. Effects of sex, weight and duration of captivity were determined by one-way analysis of variance. Significant sex differences were observed for several HCC parameters. Significant differences were also observed for select HCC variables between newly caught animals and those held in captivity for 1-12 months or longer. Comparison of this data with other non-human primate species and humans highlights similarities and disparities between species. Potential causes of interpopulation variability and relevance to the use of the African green monkey as a non-human primate model are discussed. © 2010 John Wiley & Sons A/S.

A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development.

PubMed

Makris, Susan L; Scott, Cheryl Siegel; Fox, John; Knudsen, Thomas B; Hotchkiss, Andrew K; Arzuaga, Xabier; Euling, Susan Y; Powers, Christina M; Jinot, Jennifer; Hogan, Karen A; Abbott, Barbara D; Hunter, E Sidney; Narotsky, Michael G

2016-10-01

The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties. Published by Elsevier Inc.

The U. S. Environmental Protection Agency's inhalation RfD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.

1990-10-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extra-respiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

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

Jarabek, A.M.; Menache, M.G.; Overton, J.H.

1989-01-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

Health effects of drinking water disinfectants and disinfection by-products

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

Condie, L.W.; Bercz, J.P.

This paper summarizes toxicological studies conducted with drinking water disinfectants. Toxicological effects, which are associated with the disinfectants themselves as well as with the by-products formed when disinfectants react with organic material present in water, are considered. The health impact of chemical reactions occurring between residual disinfectants and nutrients in the gastrointestinal tract is also discussed. 40 references, 5 tables.

Nanoscale reference materials for environmental, health and safety measurements: needs, gaps and opportunities.

PubMed

Stefaniak, Aleksandr B; Hackley, Vincent A; Roebben, Gert; Ehara, Kensei; Hankin, Steve; Postek, Michael T; Lynch, Iseult; Fu, Wei-En; Linsinger, Thomas P J; Thünemann, Andreas F

2013-12-01

The authors critically reviewed published lists of nano-objects and their physico-chemical properties deemed important for risk assessment and discussed metrological challenges associated with the development of nanoscale reference materials (RMs). Five lists were identified that contained 25 (classes of) nano-objects; only four (gold, silicon dioxide, silver, titanium dioxide) appeared on all lists. Twenty-three properties were identified for characterisation; only (specific) surface area appeared on all lists. The key themes that emerged from this review were: 1) various groups have prioritised nano-objects for development as "candidate RMs" with limited consensus; 2) a lack of harmonised terminology hinders accurate description of many nano-object properties; 3) many properties identified for characterisation are ill-defined or qualitative and hence are not metrologically traceable; 4) standardised protocols are critically needed for characterisation of nano-objects as delivered in relevant media and as administered to toxicological models; 5) the measurement processes being used to characterise a nano-object must be understood because instruments may measure a given sample in a different way; 6) appropriate RMs should be used for both accurate instrument calibration and for more general testing purposes (e.g., protocol validation); 7) there is a need to clarify that where RMs are not available, if "(representative) test materials" that lack reference or certified values may be useful for toxicology testing and 8) there is a need for consensus building within the nanotechnology and environmental, health and safety communities to prioritise RM needs and better define the required properties and (physical or chemical) forms of the candidate materials.

Acute contact toxicity test of insecticides (Cipermetrina 25, Lorsban 48E, Thionex 35) on honeybees in the southwestern zone of Uruguay.

PubMed

Carrasco-Letelier, Leonidas; Mendoza-Spina, Yamandú; Branchiccela, María Belén

2012-07-01

Glyphosate-resistant soybean cultivation is expanding rapidly in Uruguay, with its land area having increased by 95 times during the past 10 years. Because of the region's Neotropical conditions, insecticide use is required to ensure adequate soybean productivity. However, in areas shared by soybean crops and beekeepers - such as the southwestern zone of Uruguay (SWZU) - the use of insecticides can increase the risks of honeybee death and honey contamination. Uruguayan commercial and legal guidelines set out practices and field doses designed to prevent acute intoxication with insecticides. However, honeybees in the SWZU are predominantly a polyhybrid subspecies different from that used to set international reference values, and hence they may have a different acute toxicity response, thus rendering such precautions ineffective. The aim of this work was to assess the acute toxicity response of polyhybrid honeybees in the SWZU to cypermethrin (commercial formulation: Cipermetrina 25 Agrin®), chlorpyrifos (commercial formulation: Lorsban 48E®), and endosulfan (commercial formulation: Thionex 35®). Acute toxicity bioassays were conducted to determine the median lethal dose (LD(50)) of each insecticide for the honeybees. The results indicate that, compared with EU reference values, SWZU honeybees have a higher toxicological sensitivity to chlorpyrifos and endosulfan, and a lower toxicological sensitivity to cypermethrin, based on the commercial formulations tested. However, when these results were adjusted according to their field dose equivalents, only chlorpyrifos emerged as a potential problem for beekeeping, as the maximum recommended field dose of Lorsban 48E® for soybean crops in Uruguay is 23 times the corresponding LD(50) for honeybees in the SWZU. Copyright © 2012 Elsevier Ltd. All rights reserved.

ACToR – Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

ACToR (Aggregated Computational Toxicology Resource) is a collection of databases collated or developed by the US EPA National Center for Computational Toxicology (NCCT). More than 200 sources of publicly available data on environmental chemicals have been brought together and made searchable by chemical name and other identifiers, and by chemical structure. Data includes chemical structure, physico-chemical values, in vitro assay data and in vivo toxicology data. Chemicals include, but are not limited to, high and medium production volume industrial chemicals, pesticides (active and inert ingredients), and potential ground and drinking water contaminants.

[Vinyl chloride and 1,2-dichloroethane: classification and assessment of carcinogenicity, guidelines, threshold values, and standards developed by national and international entities, organizations, and agencies].

PubMed

Binetti, R; Costamagna, F M; Marcello, I

2001-01-01

International, national and regulatory classification, evaluation, guidelines and occupational exposure values regarding vinyl chloride and 1,2-dichloroethane, carried out by European Union (EU). Environmental Protection Agency (US EPA), International Agency for Research on Cancer (IARC), Italian National Advisory Toxicological Committee (CCTN), Occupational Safety and Health Administration (OSHA), World Health Organization (WHO), National Institute for Occupational Safety and Health (NIOSH), American Conference of Governmental Industrial Hygienists (ACGIH) and other institutions, have been considered with particular reference to the carcinogenic effects. Moreover information is reported in support of classification and evaluation and a short historical review since early 1970s, when first evidence that occupational exposure to VC could lead to angiosarcoma was published.

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

Templin-Branner, Wilma

The purpose of this training is to familiarize participants with reliable online environmental health and toxicology information, from the National Library of Medicine and other reliable sources. Skills and knowledge acquired in this training class will enable participants to access, utilize, and refer others to environmental health and toxicology information. After completing this course, participants will be able to: (1) Identify quality, accurate, and authoritative online resources pertaining to environmental health, toxicology, and related medical information; (2) Demonstrate the ability to perform strategic search techniques to find relevant online information; and (3) Apply the skills and knowledge obtained in thismore » class to their organization's health information needs. NLMs TOXNET (Toxicology Data Network) is a free, Web-based system of databases on toxicology, environmental health, hazardous chemicals, toxic releases, chemical nomenclatures, and specialty areas such as occupational health and consumer products. Types of information in the TOXNET databases include: (1) Specific chemicals, mixtures, and products; (2) Unknown chemicals; and (3) Special toxic effects of chemicals in humans and/or animals.« less

Human health risk assessment related to cyanotoxins exposure.

PubMed

Funari, Enzo; Testai, Emanuela

2008-01-01

This review focuses on the risk assessment associated with human exposure to cyanotoxins, secondary metabolites of an ubiquitous group of photosynthetic procariota. Cyanobacteria occur especially in eutrophic inland and coastal surface waters, where under favorable conditions they attain high densities and may form blooms and scums. Cyanotoxins can be grouped according to their biological effects into hepatotoxins, neurotoxins, cytotoxins, and toxins with irritating potential, also acting on the gastrointestinal system. The chemical and toxicological properties of the main cyanotoxins, relevant for the evaluation of possible risks for human health, are presented. Humans may be exposed to cyanotoxins via several routes, with the oral one being by far the most important, occurring by ingesting contaminated drinking water, food, some dietary supplements, or water during recreational activities. Acute and short-term toxic effects have been associated in humans with exposure to high levels of cyanotoxins in drinking and bathing waters. However, the chronic exposure to low cyanotoxin levels remains a critical issue. This article identifies the actual risky exposure scenarios, provides toxicologically derived reference values, and discusses open issues and research needs.

Testing for amphetamine-type stimulant (ATS) use to ascertain validity of self-reported ATS use among young female sex workers in Cambodia.

PubMed

Kab, Vannda; Evans, Jennifer; Sansothy, Neth; Stein, Ellen; Claude-Couture, Marie; Maher, Lisa; Page, Kimberly

2012-06-28

To assess concordance between self-reported amphetamine-type stimulant (ATS) use and toxicology results among young female sex workers (FSW) in Phnom Penh, Cambodia. Cross-sectional data from the Young Women's Health Study-2 (YWHS-2), a prospective study of HIV and ATS use among young (15 to 29 years) FSW in Phnom Penh, Cambodia, was analyzed. The YWHS-2 assessed sociodemographic characteristics, HIV serology, HIV risk, and ATS use by self-report and urine toxicology testing at each quarterly visit, the second of which provided data for this assessment. Outcomes include sensitivity, specificity, positive- and negative predictive values (overall and stratified by age), sex-work setting, and HIV status. Among 200 women, prevalence of positive toxicology screening for ATS use was 14% (95% confidence interval [CI], 9.2, 18.9%) and concurrent prevalence of self-reported ATS was 15.5% (95% CI, 10.4, 20.6%). The sensitivity and specificity of self-reported ATS use compared to positive toxicology test results was 89.3% (25/28), and 96.5% (166/172), respectively. The positive predictive value of self-reported ATS use was 80.6% (25/31); the negative predictive value was 98.2% (166/169). Some differences in concordance between self-report and urine toxicology results were noted in analyses stratified by age group and sex-work setting but not by HIV status. Results indicate a high prevalence of ATS use among FSW in Phnom Penh, Cambodia, and high concordance between self-reported and toxicology-test confirmed ATS use.

Using Toxicological Evidence from QSAR Models in Practice

EPA Science Inventory

The new generation of QSAR models provides supporting documentation in addition to the predicted toxicological value. Such information enables the toxicologist to explore the properties of chemical substances and to review and increase the reliability of toxicity predictions. Thi...

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY ...

EPA Pesticide Factsheets

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the “activity” portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical “properties” to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical stru

Improving substance information in USEtox® , part 1: Discussion on data and approaches for estimating freshwater ecotoxicity effect factors.

PubMed

Saouter, Erwan; Aschberger, Karin; Fantke, Peter; Hauschild, Michael Z; Bopp, Stephanie K; Kienzler, Aude; Paini, Alicia; Pant, Rana; Secchi, Michela; Sala, Serenella

2017-12-01

The scientific consensus model USEtox ® is recommended by the European Commission as the reference model to characterize life cycle chemical emissions in terms of their potential human toxicity and freshwater aquatic ecotoxicity impacts in the context of the International Reference Life Cycle Data System Handbook and the Environmental Footprint pilot phase looking at products (PEF) and organizations (OEF). Consequently, this model has been systematically used within the PEF/OEF pilot phase by 25 European Union industry sectors, which manufacture a wide variety of consumer products. This testing phase has raised some questions regarding the derivation of and the data used for the chemical-specific freshwater ecotoxicity effect factor in USEtox. For calculating the potential freshwater aquatic ecotoxicity impacts, USEtox bases the effect factor on the chronic hazard concentration (HC50) value for a chemical calculated as the arithmetic mean of all logarithmized geometric means of species-specific chronic median lethal (or effect) concentrations (L[E]C50). We investigated the dependency of the USEtox effect factor on the selection of ecotoxicological data source and toxicological endpoints, and we found that both influence the ecotoxicity ranking of chemicals and may hence influence the conclusions of a PEF/OEF study. We furthermore compared the average measure (HC50) with other types of ecotoxicity effect indicators, such as the lowest species EC50 or no-observable-effect concentration, frequently used in regulatory risk assessment, and demonstrated how they may also influence the ecotoxicity ranking of chemicals. We acknowledge that these indicators represent different aspects of a chemical's ecotoxicity potential and discuss their pros and cons for a comparative chemical assessment as performed in life cycle assessment and in particular within the PEF/OEF context. Environ Toxicol Chem 2017;36:3450-3462. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

IRIS Toxicological Review of Vanadium Pentoxide (External Review Draft)

EPA Science Inventory

This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This as...

Scientific basis and regulatory aspects for the toxicology of plant protection products in the European Union.

PubMed

Anadón, A; Martínez-Larrañaga, M R; Martínez, M A

2001-10-01

Authorization of plant protection products/agrochemicals/pesticides in the European Union is done on the basis of their toxicological properties. This paper reviews the current legislation for placing an agrochemical on the market (ie a new substance or a existing active substance), and the toxicology studies needed for inclusion of a substance in any of the annexes of the Council Directive of the European Economic Community 91/414/ EEC. Risk analysis and its steps is discussed. The "threshold toxicity" employed to allow risk characterisation of plant protection products is described, such as acceptable daily intake, acceptable operator exposure level, acute reference dose, and maximum admissible concentration in water.

Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

PubMed

Kiyosawa, Naoki; Manabe, Sunao

2016-01-01

Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

Trouble shooting in toxicopathology

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

Rousseaux, C.G.

2005-09-01

Toxicopathology, also referred to as toxicologic pathology, can be defined as the study of structural and functional changes in cells, tissues, and organs that are induced by toxicants (such as drugs, industrial and agricultural chemicals), toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and physical agents (such as heat and radiation); the investigation of the mechanisms by which these changes are induced; and the development of risk assessment and risk management policies based on such information. Toxicologic pathology primarily deals with the morphologic or structural effects of the toxicant and the mechanism by which this structural effect ismore » induced. This article highlights some of the problems that toxicologic pathologists may encounter in obtaining and interpreting pathology lesions. By alerting toxicologists to some of these issues, it is hoped that a better understanding of the use and limitations of toxicologic pathology data will occur.« less

Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and Social Media Applications in Toxicology Research.

PubMed

Carreiro, Stephanie; Chai, Peter R; Carey, Jennifer; Chapman, Brittany; Boyer, Edward W

2017-06-01

Rapid proliferation of mobile technologies in social and healthcare spaces create an opportunity for advancement in research and clinical practice. The application of mobile, personalized technology in healthcare, referred to as mHealth, has not yet become routine in toxicology. However, key features of our practice environment, such as frequent need for remote evaluation, unreliable historical data from patients, and sensitive subject matter, make mHealth tools appealing solutions in comparison to traditional methods that collect retrospective or indirect data. This manuscript describes the features, uses, and costs associated with several of common sectors of mHealth research including wearable biosensors, ingestible biosensors, head-mounted devices, and social media applications. The benefits and novel challenges associated with the study and use of these applications are then discussed. Finally, opportunities for further research and integration are explored with a particular focus on toxicology-based applications.

Pathology Report for Intraperitoneal Sodium Dichromate Exposure in Rats

DTIC Science & Technology

2015-08-12

1 2 References 1 3 Methods 1 4 Results 2 5 Discussion...Dr. Michael Madejczyk, USARMY MEDCOM USACEHR (US)). 2 References See Appendix A for a listing of references. 3 Methods Conical tubes containing...Nonproliferative Lesions of the Rat and Mouse Hepatobiliary System Toxicol Pathol. 38(7 Suppl): 5S -81S. Toxicological Study No. S.0035303-15, December

Toxicological risk assessment and prioritization of drinking water relevant contaminants of emerging concern.

PubMed

Baken, Kirsten A; Sjerps, Rosa M A; Schriks, Merijn; van Wezel, Annemarie P

2018-06-13

Toxicological risk assessment of contaminants of emerging concern (CEC) in (sources of) drinking water is required to identify potential health risks and prioritize chemicals for abatement or monitoring. In such assessments, concentrations of chemicals in drinking water or sources are compared to either (i) health-based (statutory) drinking water guideline values, (ii) provisional guideline values based on recent toxicity data in absence of drinking water guidelines, or (iii) generic drinking water target values in absence of toxicity data. Here, we performed a toxicological risk assessment for 163 CEC that were selected as relevant for drinking water. This relevance was based on their presence in drinking water and/or groundwater and surface water sources in downstream parts of the Rhine and Meuse, in combination with concentration levels and physicochemical properties. Statutory and provisional drinking water guideline values could be derived from publically available toxicological information for 142 of the CEC. Based on measured concentrations it was concluded that the majority of substances do not occur in concentrations which individually pose an appreciable human health risk. A health concern could however not be excluded for vinylchloride, trichloroethene, bromodichloromethane, aniline, phenol, 2-chlorobenzenamine, mevinphos, 1,4-dioxane, and nitrolotriacetic acid. For part of the selected substances, toxicological risk assessment for drinking water could not be performed since either toxicity data (hazard) or drinking water concentrations (exposure) were lacking. In absence of toxicity data, the Threshold of Toxicological Concern (TTC) approach can be applied for screening level risk assessment. The toxicological information on the selected substances was used to evaluate whether drinking water target values based on existing TTC levels are sufficiently protective for drinking water relevant CEC. Generic drinking water target levels of 37 μg/L for Cramer class I substances and 4 μg/L for Cramer class III substances in drinking water were derived based on these CEC. These levels are in line with previously reported generic drinking water target levels based on original TTC values and are shown to be protective for health effects of the majority of contaminants of emerging concern evaluated in the present study. Since the human health impact of many chemicals appearing in the water cycle has been studied insufficiently, generic drinking water target levels are useful for early warning and prioritization of CEC with unknown toxicity in drinking water and its sources for future monitoring. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Quantitative Ecological Risk Assessment of the Toxicological Risks from Exxon Valdez Subsurface Oil Residues to Sea Otters at Northern Knight Island, Prince William Sound, Alaska

PubMed Central

Harwell, Mark A.; Gentile, John H.; Johnson, Charles B.; Garshelis, David L.; Parker, Keith R.

2010-01-01

A comprehensive, quantitative risk assessment is presented of the toxicological risks from buried Exxon Valdez subsurface oil residues (SSOR) to a subpopulation of sea otters (Enhydra lutris) at Northern Knight Island (NKI) in Prince William Sound, Alaska, as it has been asserted that this subpopulation of sea otters may be experiencing adverse effects from the SSOR. The central questions in this study are: could the risk to NKI sea otters from exposure to polycyclic aromatic hydrocarbons (PAHs) in SSOR, as characterized in 2001–2003, result in individual health effects, and, if so, could that exposure cause subpopulation-level effects? We follow the U.S. Environmental Protection Agency (USEPA) risk paradigm by: (a) identifying potential routes of exposure to PAHs from SSOR; (b) developing a quantitative simulation model of exposures using the best available scientific information; (c) developing scenarios based on calculated probabilities of sea otter exposures to SSOR; (d) simulating exposures for 500,000 modeled sea otters and extracting the 99.9% quantile most highly exposed individuals; and (e) comparing projected exposures to chronic toxicity reference values. Results indicate that, even under conservative assumptions in the model, maximum-exposed sea otters would not receive a dose of PAHs sufficient to cause any health effects; consequently, no plausible toxicological risk exists from SSOR to the sea otter subpopulation at NKI. PMID:20862194

Data governance in predictive toxicology: A review.

PubMed

Fu, Xin; Wojak, Anna; Neagu, Daniel; Ridley, Mick; Travis, Kim

2011-07-13

Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity) and not in a toxicological sense (e.g. the quality of experimental results). This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality) and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas) of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper, data governance is identified as the new challenge in predictive toxicology, and a good use of it may provide a promising framework for developing high quality and easy accessible toxicity data repositories. This paper also identifies important research directions that require further investigation in this area.

Data governance in predictive toxicology: A review

PubMed Central

2011-01-01

Background Due to recent advances in data storage and sharing for further data processing in predictive toxicology, there is an increasing need for flexible data representations, secure and consistent data curation and automated data quality checking. Toxicity prediction involves multidisciplinary data. There are hundreds of collections of chemical, biological and toxicological data that are widely dispersed, mostly in the open literature, professional research bodies and commercial companies. In order to better manage and make full use of such large amount of toxicity data, there is a trend to develop functionalities aiming towards data governance in predictive toxicology to formalise a set of processes to guarantee high data quality and better data management. In this paper, data quality mainly refers in a data storage sense (e.g. accuracy, completeness and integrity) and not in a toxicological sense (e.g. the quality of experimental results). Results This paper reviews seven widely used predictive toxicology data sources and applications, with a particular focus on their data governance aspects, including: data accuracy, data completeness, data integrity, metadata and its management, data availability and data authorisation. This review reveals the current problems (e.g. lack of systematic and standard measures of data quality) and desirable needs (e.g. better management and further use of captured metadata and the development of flexible multi-level user access authorisation schemas) of predictive toxicology data sources development. The analytical results will help to address a significant gap in toxicology data quality assessment and lead to the development of novel frameworks for predictive toxicology data and model governance. Conclusions While the discussed public data sources are well developed, there nevertheless remain some gaps in the development of a data governance framework to support predictive toxicology. In this paper, data governance is identified as the new challenge in predictive toxicology, and a good use of it may provide a promising framework for developing high quality and easy accessible toxicity data repositories. This paper also identifies important research directions that require further investigation in this area. PMID:21752279

Investigation of a fatality due to diesel fuel No. 2 ingestion.

PubMed

Martínez, María A; Ballesteros, Salomé

2006-10-01

This paper presents a simple, rapid, reliable, and validated analytical method suited for forensic examination of diesel fuel No. 2 in biological specimens. The proposed methodology has been applied to the investigation of a forensic case with diesel fuel No. 2 ingestion. Case history and pathological and toxicological findings are described here to illustrate the toxicity of this complex hydrocarbon mixture. The toxicological significance and the possible mechanisms leading to death are also discussed. The toxicological initial screening and quantitation were performed by means of gas chromatography with flame-ionization detection and confirmation was performed using gas chromatography-mass spectrometry in total ion chromatogram mode. n-Tetradecane peak was selected to estimate diesel fuel No. 2 in all biological samples. Diesel fuel No. 2 analytical methodology was validated at five concentration levels from 5 to 400 mg/L. The method provided extraction recoveries between 89.0% and 97.9%. The limit of detection was 1 mg/L and the limit of quantitation was 5 mg/L. The linearity of the blood calibration curves was excellent with r2 values of >0.999. Intraday and interday precisions had a coefficient of variation

Profiling Developmental Toxicity of 387 Environmental Chemicals using EPA’s Toxicity Reference Database (ToxRefDB)

EPA Science Inventory

EPA's Toxicity Reference Databases (ToxRefDB) was developed by the National Center for Computational Toxicology in partnership with EPA's Office of Pesticide Programs, to store data derived from in vivo animal toxicity studies [www.epa.gov/ncct/toxrefdb/]. The initial build of To...

Recognition and Management of Pesticide Poisonings

EPA Pesticide Factsheets

The Recognition and Management of Pesticide Poisonings: 6th Edition manual gives healthcare providers a quick reference resource for the best toxicology and treatment information for patients with pesticide exposures.

Red blood cell acetylcholinesterase activity among healthy dwellers of an agrarian region in Sri Lanka: a descriptive cross-sectional study.

PubMed

Rathish, Devarajan; Senavirathna, Indika; Jayasumana, Channa; Agampodi, Suneth

2018-06-21

Assessment of acetylcholinesterase-inhibitor insecticide (AChEII) toxicity depends on the measurement of red blood cell acetylcholinesterase (RBC-AChE) activity. Its interpretation requires baseline values which is lacking in scientific literature. We aim to find the measures of central tendency and variation for RBC-AChE activity among dwellers of Anuradhapura, where the use and abuse of AChEIIs were rampant for the last few decades. A descriptive cross-sectional study with a community-based sampling for 100 healthy non-farmers (male:female = 1:1) was done using pre-determined selection criteria. Duplicate measurements of RBC-AChE activity were performed according to the modified Ellman procedure. Pearson's correlation and regression analysis were sort for RBC-AChE activity against its possible determinants. RBC-AChE activity had a mean of 449.8 (SD 74.2) mU/μM Hb with a statistical power of 0.847. It was similar to values of "healthy controls" from previous Sri Lankan toxicological studies but was low against international reference value [586.1 (SD 65.1) mU/μM Hb]. None of the possible determinants showed a significant strength of relationship with RBC-AChE activity. The baseline RBC-AChE activity among people of Anuradhapura is low in comparison with international reference values. This arises a need to find a causative mechanism.

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Clinical toxicology calibrator. 862.3200 Section 862.3200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... that are used in the determination of values in the measurement of substances in human specimens. A...

Green Toxicology: a strategy for sustainable chemical and material development.

PubMed

Crawford, Sarah E; Hartung, Thomas; Hollert, Henner; Mathes, Björn; van Ravenzwaay, Bennard; Steger-Hartmann, Thomas; Studer, Christoph; Krug, Harald F

2017-01-01

Green Toxicology refers to the application of predictive toxicology in the sustainable development and production of new less harmful materials and chemicals, subsequently reducing waste and exposure. Built upon the foundation of "Green Chemistry" and "Green Engineering", "Green Toxicology" aims to shape future manufacturing processes and safe synthesis of chemicals in terms of environmental and human health impacts. Being an integral part of Green Chemistry, the principles of Green Toxicology amplify the role of health-related aspects for the benefit of consumers and the environment, in addition to being economical for manufacturing companies. Due to the costly development and preparation of new materials and chemicals for market entry, it is no longer practical to ignore the safety and environmental status of new products during product development stages. However, this is only possible if toxicologists and chemists work together early on in the development of materials and chemicals to utilize safe design strategies and innovative in vitro and in silico tools. This paper discusses some of the most relevant aspects, advances and limitations of the emergence of Green Toxicology from the perspective of different industry and research groups. The integration of new testing methods and strategies in product development, testing and regulation stages are presented with examples of the application of in silico, omics and in vitro methods. Other tools for Green Toxicology, including the reduction of animal testing, alternative test methods, and read-across approaches are also discussed.

Environmental Health and Toxicology Resources of the United States National Library of Medicine

PubMed Central

Hochstein, Colette; Arnesen, Stacey; Goshorn, Jeanne

2009-01-01

For over 40 years, the National Library of Medicine’s (NLM) Toxicology and Environmental Health Information Program (TEHIP) has worked to organize and to provide access to an extensive array of environmental health and toxicology resources. During these years, the TEHIP program has evolved from a handful of databases developed primarily for researchers to a broad range of products and services that also serve industry, students, and the general public. TEHIP’s resources include TOXNET® , a collection of databases, including online handbooks, bibliographic references, information on the release of chemicals in the environment, and a chemical dictionary. TEHIP also produces several resources aimed towards the general public, such as the Household Products Database , which helps users explore chemicals often found in common household products, and Tox Town® , an interactive guide to commonly encountered toxic substances, health, and the environment. This paper introduces some of NLM’s environmental health and toxicology resources. PMID:17915629

Accuracy of information on substance use recorded in medical charts of patients with intentional drug overdose.

PubMed

Tournier, Marie; Molimard, Mathieu; Titier, Karine; Cougnard, Audrey; Bégaud, Bernard; Gbikpi-Benissan, Georges; Verdoux, Hélène

2007-07-30

Psychoactive substance use is a risk factor for suicidal behavior and current intoxication increases the likelihood of serious intentional drug overdose (IDO). The objective was to assess the accuracy of information on substance use recorded in medical charts using toxicological assays as a reference in subjects admitted for IDO to an emergency department. Patients (n=1190) consecutively admitted for IDO were included. Information on substance use was recorded in routine practice by the emergency staff and toxicological assays (cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, LSD) were carried out in urine samples collected as part of routine management. The information on substance use was recorded in medical charts for 24.4% of subjects. A third of subjects (27.5%) were positive for toxicological assays. Recorded substance use allowed correct classification of nearly 80% of subjects. However, specificity (88.6%) was better than sensitivity (54.2%). Compared with toxicological assays, medical records allowed identification of only half of the subjects with current substance use. The usefulness of systematic toxicological assays during hospitalization for IDO should be assessed in further studies exploring whether such information allows medical management to be modified and contributes to improving prognosis.

An Integrated Chemical Environment to Support 21st-Century Toxicology.

PubMed

Bell, Shannon M; Phillips, Jason; Sedykh, Alexander; Tandon, Arpit; Sprankle, Catherine; Morefield, Stephen Q; Shapiro, Andy; Allen, David; Shah, Ruchir; Maull, Elizabeth A; Casey, Warren M; Kleinstreuer, Nicole C

2017-05-25

SUMMARY : Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21 TM /ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759.

An Integrated Chemical Environment to Support 21st-Century Toxicology

PubMed Central

Bell, Shannon M.; Phillips, Jason; Sedykh, Alexander; Tandon, Arpit; Sprankle, Catherine; Morefield, Stephen Q.; Shapiro, Andy; Allen, David; Shah, Ruchir; Maull, Elizabeth A.; Casey, Warren M.

2017-01-01

Summary: Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21TM/ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759 PMID:28557712

Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

2016-09-01

To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human exposure to chemical mixtures: Challenges for the integration of toxicology with epidemiology data in risk assessment.

PubMed

Hernández, Antonio F; Tsatsakis, Aristidis M

2017-05-01

Little is known about the potential adverse effects from longterm exposure to complex mixtures at low doses, close to health-based reference values. Traditional chemical-specific risk assessment based on animal testing may be insufficient and the lack of toxicological studies on chemical mixtures remains a major regulatory challenge. Hence, new methodologies on cumulative risk assessment are being developed but still present major limitations. Evaluation of chemical mixture effects requires an integrated and systematic approach and close collaboration across different scientific fields, particularly toxicology, epidemiology, exposure science, risk assessment and statistics for a proper integration of data from all these disciplines. Well designed and conducted epidemiological studies can take advantage of this new paradigm and can provide insight to support the correlation between humans low-dose exposures and diseases, thus avoiding the uncertainty associated with extrapolation across species. In this regard, human epidemiology studies may play a significant role in the new vision of toxicity testing. However, this type of information has not been fully considered in risk assessment, mainly due to the inherent limitations of epidemiologic studies. An integrated approach of in vivo, in vitro and in silico data, together with systematic reviews or meta-analysis of high quality epidemiological studies will improve the robustness of risk assessment of chemical mixtures and will provide a stronger basis for regulatory decisions. The ultimate goal is that experimental and mechanistic data can lend support and biological plausibility to the human epidemiological observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Scientific procedures on living animals in Great Britain in 2003: the facts, figures and consequences.

PubMed

Hudson, Michelle; Bhogal, Nirmala

2004-11-01

The statistics for animal procedures performed in 2003 were recently released by the Home Office. They indicate that, for the second year running, there was a significant increase in the number of laboratory animal procedures undertaken in Great Britain. The species and genera used, the numbers of toxicology and non-toxicology procedures, and the overall trends, are described. The implications of these latest statistics are discussed with reference to key areas of interest and to the impact of existing regulations and pending legislative reforms.

[The overview of research on toxicological (forensic) chemistry based on the materials of the abstracts of dissertation theses. The forms and modes of information].

PubMed

Gorbacheva, N A; Orlova, A M

2012-01-01

The authors discuss the system of information about investigations on toxicological (forensic) chemistry carried out for obtaining the scientific degree as it has formed in this country. They present a review and a list of theses and their abstracts in this discipline defended during the period from 1936 to 2010. The analysis of the themes of the studies is performed with reference to the dynamics of preparation of the theses in the Soviet and post-Soviet periods.

Fathead minnow genome sequencing and assembly

EPA Pesticide Factsheets

The dataset provides the URLs for accessing the genome sequence data and two draft assemblies as well as fathead minnow genotyping data associated with estimating the heterozygosity of the in-bred line.This dataset is associated with the following publication:Burns, F., L. Cogburn, G. Ankley , D. Villeneuve , E. Waits , Y. Chang, V. Llaca, S. Deschamps, R. Jackson, and R. Hoke. Sequencing and De novo Draft Assemblies of the Fathead Minnow (Pimphales promelas)Reference Genome. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 35(1): 212-217, (2016).

DEMO: ECOTOX Knowledgebase

EPA Science Inventory

The ECOTOXicology Knowledgebase (ECOTOX), is a comprehensive, curated database that summarizes toxicology data fromsingle chemical exposure studies to aquatic life, terrestrial plants, and wildlife. The ECOTOX Knowledgebase currently has curated data from over 47,000 references a...

Essential Nursing References.

ERIC Educational Resources Information Center

Nursing and Health Care Perspectives, 2000

2000-01-01

This partially annotated bibliography contains these categories: abstract sources, archives, audiovisuals, bibliographies, databases, dictionaries, directories, drugs/toxicology/environmental health, grant resources, histories, indexes, Internet resources, reviews, statistical sources, and writers' manuals and guides. A supplement lists Canadian…

DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC DATA.

EPA Science Inventory

The pharmaceutical industry has demonstrated success in integrating of chemogenomic knowledge into predictive toxicological models, due in part to industry's access to large amounts of proprietary and commercial reference genomic data sets.

Monitoring compliance to therapy during addiction treatments by means of hair analysis for drugs and drug metabolites using capillary zone electrophoresis coupled to time-of-flight mass spectrometry.

PubMed

Gottardo, Rossella; Fanigliulo, Ameriga; Sorio, Daniela; Liotta, Eloisa; Bortolotti, Federica; Tagliaro, Franco

2012-03-10

Capillary electrophoresis coupled to time-of-flight mass spectrometry was used in the present work for the determination of therapeutic and abused drugs and their metabolites in the hair of subjects undergoing addiction treatments, in order to monitor their compliance to therapy. For this purpose a rapid, qualitative drug screening method was adopted based on capillary electrophoresis hyphenated with time-of-flight mass spectrometry, which had earlier been developed and validated for the forensic-toxicological analysis of hair, limitedly to illicit/abused drugs [1]. Sampling of hair was carried out in order to refer to a time window of about two months from the date of sampling (i.e. 2cm ca. from cortex). A single extraction procedure was applied, allowing the determination in the hair matrix of "drugs of abuse" referred to the past abuses, and therapeutic drugs prescribed in the detoxification program as well as their metabolites. Analyte identification was based on accurate mass measurements and comparison of isotope patterns, providing the most likely matching between accurate mass value and elemental formula. Small molecules (<500Da) of forensic and toxicological interest could be identified unambiguously using mass spectrometric conditions tailored to meet a mass accuracy ≤5ppm. In the present study, the proposed approach proved suitable for the rapid broad spectrum screening of hair samples, although needing further confirmation of results by using fragmentation mass spectrometry. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Development of dietary-based toxic reference values to assess the risk of chlorophacinone to non-target raptorial birds

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Shultz, S. L.; Horak, Katherine E.; Abbo, Benjamin G.; Volker, Steven F.; Timms, R. M.; O'Brien, J. M.

2014-01-01

Regulatory changes in the use of some second-generation anticoagulant rodenticides in parts of North America may result in expanded use of first-generation anticoagulant rodenticides (FGARs). Recent toxicological studies with captive raptors have demonstrated that these species are considerably more sensitive to the FGAR diphacinone than traditional avian wildlife test species (mallard, bobwhite). We have now examined the toxicity of the FGAR chlorophacinone (CPN) to American kestrels fed rat tissue mechanically-amended with CPN, or rat tissue containing biologically-incorporated CPN, for 7 days. Nominal CPN concentrations in these diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and actual CPN concentration in diets were analytically verified as being close to target values. Food intake was consistent among groups, body weight fluctuated by less than 6%, exposure and adverse effects were generally dose-dependent, and there were no dramatic differences in toxicity between mechanically-amended and biologically-incorporated CPN diets. Using benchmark dose statistical methods, toxic reference values at which clotting times were prolonged in 50% of the kestrels was estimated to be about 80 µg CPN consumed/kg body weight-day for prothrombin time and 40 µg CPN/kg body weight-day for Russell's viper venom time. Based upon carcass CPN residues reported in rodents from field baiting studies, empirical measures of food consumption in kestrels, and dietary-based toxic reference values derived from the 7-day exposure scenario, some free-ranging raptors consuming CPN exposed prey might exhibit coagulopathy and hemorrhage. These sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of exposed birds.

The Toxicity Data Landscape for Environmental Chemicals

PubMed Central

Judson, Richard; Richard, Ann; Dix, David J.; Houck, Keith; Martin, Matthew; Kavlock, Robert; Dellarco, Vicki; Henry, Tala; Holderman, Todd; Sayre, Philip; Tan, Shirlee; Carpenter, Thomas; Smith, Edwin

2009-01-01

Objective Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. Data sources We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. Data extraction ACToR contains chemical structure information; physical–chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. Data synthesis We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. Conclusions Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program. PMID:19479008

Could ecological thresholds of toxicological concern (eco-TTCs) be used to support development of ambient water quality criteria?

EPA Science Inventory

The Threshold of Toxicologic Concern (TTC) is an approach used for a decades in human hazard assessment. A TTC establishes an exposure level for a chemical below which no appreciable risk to human health is expected based upon a de minimis value for toxicity identified for many ...

Investigation of fatalities due to acute gasoline poisoning.

PubMed

Martínez, María A; Ballesteros, Salomé

2005-10-01

This paper presents a simple, rapid, reliable, and validated method suited for forensic examination of gasoline in biological samples. The proposed methodology has been applied to the investigation of four fatal cases due to gasoline poisoning that occurred in Spain in 2003 and 2004. Case histories and pathological and toxicological findings are described in order to illustrate the danger of gasoline exposure under several circumstances. Gasoline's tissular distribution, its quantitative toxicological significance, and the possible mechanisms leading to death are also discussed. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography (GC) with flame-ionization detection, and confirmation was performed using GC-mass spectrometry in total ion chromatogram mode. m,p-Xylene peak was selected to estimate gasoline in all biological samples. Gasoline analytical methodology was validated at five concentration levels from 1 to 100 mg/L. The method provided extraction recoveries between 77.6% and 98.3%. The limit of detection was 0.3 mg/L, and the limit of quantitation was 1.0 mg/L. The linearity of the blood calibration curves was excellent with r2 values of > 0.997. Intraday and interday precisions had a coefficient of variation < or = 5.4% in all cases. Cases 1 and 2 consist of the accidental inhalation of gasoline vapor inside a small enclosed space. Case 3 is a death by recreational gasoline inhalation in a male adolescent. Heart blood concentrations were 28.4, 18.0, and 38.3 mg/L, respectively; liver concentrations were 41.4, 52.9, and 124.2 mg/kg, respectively; and lung concentrations were 5.6, 8.4, and 39.3 mg/kg, respectively. Case 4 was an accidental death due to gasoline ingestion of a woman with senile dementia. Peripheral blood concentration was 122.4 mg/L, the highest in our experience. Because pathological findings were consistent with other reports of gasoline intoxication and constituents of gasoline were found in the body, cause of death was attributed to acute gasoline intoxication. As a rule, this kind of poisoning offers little difficulty in diagnosis because there is a history of exposure, and the odor usually clings to the clothes, skin, or gastric contents. However, anatomic autopsy findings will be nonspecific and therefore toxicological analysis is necessary. There is a paucity of recent references regarding analytical and toxicological data, and this article provides evidence about toxic concentrations and is a useful adjunct to the postmortem toxicological interpretation of fatalities if the decedent has been involved in gasoline use.

Systems Toxicology: The Future of Risk Assessment.

PubMed

Sauer, John Michael; Hartung, Thomas; Leist, Marcel; Knudsen, Thomas B; Hoeng, Julia; Hayes, A Wallace

2015-01-01

Risk assessment, in the context of public health, is the process of quantifying the probability of a harmful effect to individuals or populations from human activities. With increasing public health concern regarding the potential risks associated with chemical exposure, there is a need for more predictive and accurate approaches to risk assessment. Developing such an approach requires a mechanistic understanding of the process by which xenobiotic substances perturb biological systems and lead to toxicity. Supplementing the shortfalls of traditional risk assessment with mechanistic biological data has been widely discussed but not routinely implemented in the evaluation of chemical exposure. These mechanistic approaches to risk assessment have been generally referred to as systems toxicology. This Symposium Overview article summarizes 4 talks presented at the 35th Annual Meeting of the American College of Toxicology. © The Author(s) 2015.

An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events.

PubMed

Haller, Christine A; Anderson, Ilene B; Kim, Susan Y; Blanc, Paul D

2002-01-01

There has been a recent proliferation of medical reference texts intended to guide practitioners whose patients use herbal therapies. We systematically assessed six herbal reference texts to evaluate the information they contain on herbal toxicity. We selected six major herbal references published from 1996 to 2000 to evaluate the adequacy of their toxicological information in light of published adverse events. To identify herbs most relevant to toxicology, we reviewed herbal-related calls to our regional California Poison Control System, San Francisco division (CPCS-SF) in 1998 and identified the 12 herbs (defined as botanical dietary supplements) most frequently involved in these CPCS-SF referrals. We searched Medline (1966 to 2000) to identify published reports of adverse effects potentially related to these same 12 herbs. We scored each herbal reference text on the basis of information inclusiveness for the target 12 herbs, with a maximal overall score of 3. The herbs, identified on the basis of CPCS-SF call frequency were: St John's wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe and kava kava. The overall herbal reference scores ranged from 2.2 to 0.4 (median 1.1). The Natural Medicines Comprehensive Database received the highest overall score and was the most complete and useful reference source. All of the references, however, lacked sufficient information on management of herbal medicine overdose, and several had incorrect overdose management guidelines that could negatively impact patient care. Current herbal reference texts do not contain sufficient information for the assessment and management of adverse health effects of botanical therapies.

Computational Toxicology at the US EPA | Science Inventory ...

EPA Pesticide Factsheets

Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in America’s air, water, and hazardous-waste sites. The ORD Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the EPA Science to Achieve Results (STAR) program. Key intramural projects of the CTRP include digitizing legacy toxicity testing information toxicity reference database (ToxRefDB), predicting toxicity (ToxCast™) and exposure (ExpoCast™), and creating virtual liver (v-Liver™) and virtual embryo (v-Embryo™) systems models. The models and underlying data are being made publicly available t

[Continuous challenges in Japanese forensic toxicology practice: strategy to address specific goals].

PubMed

Kageura, Mitsuyoshi

2002-09-01

In this paper, the status quo of forensic toxicology in Japan and the West is surveyed and a strategy to address future goals of Japanese forensic toxicology is proposed. Forensic toxicology in the West consists of three main areas--post-mortem forensic toxicology, human-performance forensic toxicology and forensic urine drug testing. In Japan, post-mortem forensic toxicology is practiced in university forensic medicine departments while most of the human-performance forensic toxicology is carried out in police laboratories. However, at least at present, strictly controlled workplace urine drug testing is not being performed, despite the abuse of drugs even by uniformed members of the National Defence Forces and police. For several years, the author has been introducing Western forensic toxicology guidelines and recommendations, translated into Japanese with the help of Western forensic toxicologists, to Japanese forensic toxicologists. Western forensic toxicology practice is at an advanced stage, whereas Japanese practice is in a critical condition and holds many problems awaiting solution, as exemplified by the urine drug testing in police laboratories. There is never any sample left for re-examination by the defence in all cases, though the initial volume of the urine sample available for examination is 30-50 ml. Only one organisation carries out everything from sampling to reporting and, in addition, the parent drug and its metabolites are not quantified. It is clear that the police laboratories do not work within good laboratory practice guidelines, nor do they have quality manuals or standard operating procedures manuals. A basic change in Japanese forensic toxicology practice is now essential. The author strongly recommends that, first of all, Japanese toxicologists should prepare forensic toxicology guidelines based on the Western models. The guidelines would progress the following objectives for forensic toxicology laboratories: 1) to have documented good laboratory practice standards; 2) to have a quality control system including a quality manual and standard operating procedures manual; 3) to have some degree of compulsion to implement quality assurance both through their own internal efforts and by appropriate remedial actions based on the results of an external proficiency testing scheme. For forensic toxicologists, the implications are that they should be: 1) responsible for ensuring that laboratory practices are performed under satisfactory conditions and 2) required to be certified as a forensic toxicology specialist in order to prove their forensic toxicology ability. For their part, governments should: 1) carry out administrative reforms related to forensic toxicology; 2) simplify the procedure for obtaining certified reference materials; 3) introduce a strict workplace urine drug testing programme for government employees, at least for those related to law enforcement. When all of these objectives have been realised, the specific goal will be achieved through which Japanese forensic toxicology is able, in practice, to fulfill its responsibility to society.

Choosing the right laboratory: a review of clinical and forensic toxicology services for urine drug testing in pain management.

PubMed

Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L

2015-01-01

Urine drug testing (UDT) services are provided by a variety of clinical, forensic, and reference/specialty laboratories. These UDT services differ based on the principal activity of the laboratory. Clinical laboratories provide testing primarily focused on medical care (eg, emergency care, inpatients, and outpatient clinics), whereas forensic laboratories perform toxicology tests related to postmortem and criminal investigations, and drug-free workplace programs. Some laboratories now provide UDT specifically designed for monitoring patients on chronic opioid therapy. Accreditation programs for clinical laboratories have existed for nearly half a century, and a federal certification program for drug-testing laboratories was established in the 1980s. Standards of practice for forensic toxicology services other than workplace drug testing have been established in recent years. However, no accreditation program currently exists for UDT in pain management, and this review considers several aspects of laboratory accreditation and certification relevant to toxicology services, with the intention to provide guidance to clinicians in their selection of the appropriate laboratory for UDT surveillance of their patients on opioid therapy.

Opioids in the Frame of New Psychoactive Substances Network: A Complex Pharmacological and Toxicological Issue.

PubMed

Ventura, Ludovic; Carvalho, Felix; Dinis-Oliveira, Ricardo Jorge

2018-01-01

New psychoactive substances (NPS), often referred to as "legal highs" or "designer drugs", are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS. Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin. Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

State-of-the-art of bone marrow analysis in forensic toxicology: a review.

PubMed

Cartiser, Nathalie; Bévalot, Fabien; Fanton, Laurent; Gaillard, Yvan; Guitton, Jérôme

2011-03-01

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

ToxGuides: Quick Reference Pocket Guide for Toxicological Profiles

MedlinePlus

... Favorites Del.icio.us Digg Facebook Google Bookmarks Yahoo MyWeb Get email updates To receive email updates ... Favorites Del.icio.us Digg Facebook Google Bookmarks Yahoo MyWeb Page last reviewed: January 21, 2015 Page ...

n-Ethyl Pentylone-Related Deaths in Alabama.

PubMed

Atherton, Daniel; Dye, Daniel; Robinson, C Andrew; Beck, Rachel

2018-05-16

n-Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind-altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS-stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation. © 2018 American Academy of Forensic Sciences.

Evidence-based toxicology for the 21st century: opportunities and challenges.

PubMed

Stephens, Martin L; Andersen, Melvin; Becker, Richard A; Betts, Kellyn; Boekelheide, Kim; Carney, Ed; Chapin, Robert; Devlin, Dennis; Fitzpatrick, Suzanne; Fowle, John R; Harlow, Patricia; Hartung, Thomas; Hoffmann, Sebastian; Holsapple, Michael; Jacobs, Abigail; Judson, Richard; Naidenko, Olga; Pastoor, Tim; Patlewicz, Grace; Rowan, Andrew; Scherer, Roberta; Shaikh, Rashid; Simon, Ted; Wolf, Douglas; Zurlo, Joanne

2013-01-01

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on "Evidence-based Toxicology for the 21st Century: Opportunities and Challenges" in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathway-based testing methods consistent with the 2007 National Research Council report on "Toxicity Testing in the 21st Century" as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches.

Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

PubMed

Grandjean, P

2015-12-01

A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. © The Author(s) 2015.

IRIS Toxicological Review of 2,2',4,4'-Tetrabromodiphenyl ...

EPA Pesticide Factsheets

The U.S. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessments of congeners of polybrominated diphenyl ethers (PDBEs), this review is about 2,2',4,4'-Tetrabromodiphenyl Ether, or commonly referred to as tetraBDE (BDE-47). Following the external peer review this assessment will appear in the Integrated Risk Information System (IRIS) database. Peer review will ensure that science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. EPA is updating the Integrated Risk Information System (IRIS) health assessments for the PBDEs.

Preparation and characterization of "Libby Amphibole" toxicological testing material

USGS Publications Warehouse

Lowers, Heather; Wilson, Stephen A.; Hoefen, Todd M.; Benzel, William M.; Meeker, Gregory P.

2012-01-01

The U.S. Environmental Protection Agency (USEPA) began work in Libby, Mont. in 1999 when an Emergency Response Team was sent to investigate local concern and media reports regarding asbestos-contaminated vermiculite. Since that time, the site has been granted Superfund status and site remediation to a safe level of asbestos has been ongoing. The amphibole asbestos from the Vermiculite Mountain vermiculite deposit near Libby, Mont. (Libby amphibole) is unusual in the sense that it is currently not classified as one of the regulated six asbestos minerals—chrysotile (a serpentine mineral) and the amphibole minerals amosite (asbestiform cummingtonite-grunerite), crocidolite (asbestiform riebeckite), asbestiform anthophyllite, asbestiform tremolite, and asbestiform actinolite. The amphiboles from the Vermiculite Mountain vermiculite deposit, primarily winchite and richterite, are related to tremolite and in the past have been referred to as sodium-rich tremolite or soda tremolite (Larsen, 1942; Boettcher, 1966; Wylie and Verkouteren, 2000; Gunter and others, 2003; Meeker and others, 2003). The public health issues in Libby, Mont. have brought to light many of the inconsistencies in the literature regarding fiber characteristics, nomenclature, and toxicology. To better understand the toxicological characteristics of the Libby amphibole, investigators require a sufficient quantity of material representing the range of fibrous amphiboles present in the vicinity of Vermiculite Mountain to use in toxicology studies. The material collected in 2000 (Meeker and others, 2003) has been exhausted and a second collection and preparation effort, funded by the USEPA, was conducted in 2007. Both the 2000 (LA2000) and 2007 (LA2007) materials were generated to support research needs identified by the USEPA and the National Toxicology Program, and new in-vivo and in-vitro toxicology studies are underway. This Open-File Report describes the process of preparation and summarizes the chemistry and mineralogy of the LA2007 toxicological testing material.

Assessment of the potential human health risks from exposure to complex substances in accordance with REACH requirements. "White spirit" as a case study.

PubMed

McKee, Richard H; Tibaldi, Rosalie; Adenuga, Moyinoluwa D; Carrillo, Juan-Carlos; Margary, Alison

2018-02-01

The European chemical control regulation (REACH) requires that data on physical/chemical, toxicological and environmental hazards be compiled. Additionally, REACH requires formal assessments to ensure that substances can be safely used for their intended purposes. For health hazard assessments, reference values (Derived No Effect levels, DNELs) are calculated from toxicology data and compared to estimated exposure levels. If the ratio of the predicted exposure level to the DNEL, i.e. the Risk Characterization Ratio (RCR), is less than 1, the risk is considered controlled; otherwise, additional Risk Management Measures (RMM) must be applied. These requirements pose particular challenges for complex substances. Herein, "white spirit", a complex hydrocarbon solvent, is used as an example to illustrate how these procedures were applied. Hydrocarbon solvents were divided into categories of similar substances. Representative substances were identified for DNEL determinations. Adjustment factors were applied to the no effect levels to calculate the DNELs. Exposure assessments utilized a standardized set of generic exposure scenarios (GES) which incorporated exposure predictions for solvent handling activities. Computer-based tools were developed to automate RCR calculations and identify appropriate RMMs, allowing consistent communications to users via safety data sheets. Copyright © 2017 ExxonMobil Biomedical Sciences Inc. Published by Elsevier Inc. All rights reserved.

Evolving the Principles and Practice of Validation for New Alternative Approaches to Toxicity Testing.

PubMed

Whelan, Maurice; Eskes, Chantra

Validation is essential for the translation of newly developed alternative approaches to animal testing into tools and solutions suitable for regulatory applications. Formal approaches to validation have emerged over the past 20 years or so and although they have helped greatly to progress the field, it is essential that the principles and practice underpinning validation continue to evolve to keep pace with scientific progress. The modular approach to validation should be exploited to encourage more innovation and flexibility in study design and to increase efficiency in filling data gaps. With the focus now on integrated approaches to testing and assessment that are based on toxicological knowledge captured as adverse outcome pathways, and which incorporate the latest in vitro and computational methods, validation needs to adapt to ensure it adds value rather than hinders progress. Validation needs to be pursued both at the method level, to characterise the performance of in vitro methods in relation their ability to detect any association of a chemical with a particular pathway or key toxicological event, and at the methodological level, to assess how integrated approaches can predict toxicological endpoints relevant for regulatory decision making. To facilitate this, more emphasis needs to be given to the development of performance standards that can be applied to classes of methods and integrated approaches that provide similar information. Moreover, the challenge of selecting the right reference chemicals to support validation needs to be addressed more systematically, consistently and in a manner that better reflects the state of the science. Above all however, validation requires true partnership between the development and user communities of alternative methods and the appropriate investment of resources.

Health Assessment Document for Diesel Emissions (External Review Draft, 1994) - Volume 1

EPA Science Inventory

This report on the health effects of diesel combustion emissions, includes a quantitative cancer risk assessment, and a reference concentration (non-cancer) for lifetime exposure; atmospheric concentrations, transport, and transformation; inhalation dosimetry; animal toxicology; ...

Animal models of toxicology testing: the role of pigs.

PubMed

Helke, Kristi L; Swindle, Marvin Michael

2013-02-01

In regulatory toxicological testing, both a rodent and non-rodent species are required. Historically, dogs and non-human primates (NHP) have been the species of choice of the non-rodent portion of testing. The pig is an appropriate option for these tests based on metabolic pathways utilized in xenobiotic biotransformation. This review focuses on the Phase I and Phase II biotransformation pathways in humans and pigs and highlights the similarities and differences of these models. This is a growing field and references are sparse. Numerous breeds of pigs are discussed along with specific breed differences in these enzymes that are known. While much available data are presented, it is grossly incomplete and sometimes contradictory based on methods used. There is no ideal species to use in toxicology. The use of dogs and NHP in xenobiotic testing continues to be the norm. Pigs present a viable and perhaps more reliable model of non-rodent testing.

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

Inhalation TTC values: A new integrative grouping approach considering structural, toxicological and mechanistic features.

PubMed

Tluczkiewicz, I; Kühne, R; Ebert, R-U; Batke, M; Schüürmann, G; Mangelsdorf, I; Escher, S E

2016-07-01

The present publication describes an integrative grouping concept to derive threshold values for inhalation exposure. The classification scheme starts with differences in toxicological potency and develops criteria to group compounds into two potency classes, namely toxic (T-group) or low toxic (L-group). The TTC concept for inhalation exposure is based on the TTC RepDose data set, consisting of 296 organic compounds with 608 repeated-dose inhalation studies. Initially, 21 structural features (SFs) were identified as being characteristic for compounds of either high or low NOEC values (Schüürmann et al., 2016). In subsequent analyses these SF groups were further refined by taking into account structural homogeneity, type of toxicological effect observed, differences in absorption, metabolism and mechanism of action (MoA), to better define their structural and toxicological boundaries. Differentiation of a local or systemic mode of action did not improve the classification scheme. Finally, 28 groups were discriminated: 19 T-groups and 9 L-groups. Clearly distinct thresholds were derived for the T- and L-toxicity groups, being 2 × 10(-5) ppm (2 μg/person/day) and 0.05 ppm (4260 μg/person/day), respectively. The derived thresholds and the classification are compared to the initial mainly structure driven grouping (Schüürmann et al., 2016) and to the Cramer classification. Copyright © 2016 Elsevier Inc. All rights reserved.

Toxicological importance of human biomonitoring of metallic and metalloid elements in different biological samples.

PubMed

Gil, F; Hernández, A F

2015-06-01

Human biomonitoring has become an important tool for the assessment of internal doses of metallic and metalloid elements. These elements are of great significance because of their toxic properties and wide distribution in environmental compartments. Although blood and urine are the most used and accepted matrices for human biomonitoring, other non-conventional samples (saliva, placenta, meconium, hair, nails, teeth, breast milk) may have practical advantages and would provide additional information on health risk. Nevertheless, the analysis of these compounds in biological matrices other than blood and urine has not yet been accepted as a useful tool for biomonitoring. The validation of analytical procedures is absolutely necessary for a proper implementation of non-conventional samples in biomonitoring programs. However, the lack of reliable and useful analytical methodologies to assess exposure to metallic elements, and the potential interference of external contamination and variation in biological features of non-conventional samples are important limitations for setting health-based reference values. The influence of potential confounding factors on metallic concentration should always be considered. More research is needed to ascertain whether or not non-conventional matrices offer definitive advantages over the traditional samples and to broaden the available database for establishing worldwide accepted reference values in non-exposed populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone.

PubMed

Escobedo-González, René; Vargas-Requena, Claudia Lucia; Moyers-Montoya, Edgar; Aceves-Hernández, Juan Manuel; Nicolás-Vázquez, María Inés; Miranda-Ruvalcaba, René

2017-06-25

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC 50 value ranking, i.e: indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.

A review on phytochemistry and ethnopharmacological aspects of genus Calendula

PubMed Central

Arora, Disha; Rani, Anita; Sharma, Anupam

2013-01-01

This review includes 84 references on the genus Calendula (Asteraceae) and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies and toxicology of the prominent species of Calendula. Triterpene alcohols, triterpene saponins, flavonoids, carotenoids and polysaccharides constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these Calendula officinalis Linn., has been traditionally used in the treatment of various skin tumors, dermatological lesions, ulcers, swellings and nervous disorders as well as almost 200 cosmetic formulations, i.e., creams, lotions, shampoos. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Calendula species has been emphasized with a view to establish their multifarious biological activities and mode of action. PMID:24347926

Mineral content of Chinese medicinal herbs used as diuretic treatments for Taiwanese children.

PubMed

Chen, Chien-Yi

2005-01-01

Eighteen major, minor and trace elements in 12 Chinese medicinal herbs commonly consumed by Taiwanese Children as diuretics were determined by instrumental neutron activation analysis (INAA). Dried and powdered herb samples were irradiated in a neutron flux of ca. 2 x 10(12) n/cm2 s under separate short and long irradiation schemes. Lichen (IAEA-336) was used as the reference standard, and tomato leaves (NIST-SRM 1570a) were employed for cross-checking the accuracy of the results. INAA was shown to be a reliable multi-element analytical method for determining the content of both toxicologically and nutritionally important minerals in Chinese medicinal herbs. Determined elements were present in the dried herbs in concentrations ranging from 10(4) to 10(-3) microg/g. The mineral contents and the maximum daily intake values of the tested herbs were compared with published values and with the recommended daily intakes for Taiwanese children as specified by the World Health Organization.

Characterizing "Adversity" of Pathology Findings in ...

EPA Pesticide Factsheets

The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

40 CFR 158.2230 - Toxicology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... systems (collectively referred to as HVAC&R). Instead, two 90-day toxicity tests, one by the dermal route... causes treatment-related neurological effects in developing animals, following pre- or post-natal... individual test, including specific conditions, qualifications, or exceptions are listed in paragraph (h) of...

Barium and Compounds

Integrated Risk Information System (IRIS)

EPA / 635 / R - 05 / 001 www.epa.gov / iris TOXICOLOGICAL REVIEW OF BARIUM AND COMPOUNDS ( CAS No . 7440 - 39 - 3 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) March 1998 Minor revisions January 1999 Reference dose revised June 2005 U.S . Environmental Protec

Computerized Drug Information Services

ERIC Educational Resources Information Center

And Others; Smith, Daniel R.

1972-01-01

To compare computerized services in chemistry, pharmacology, toxicology, and clinical medicine of pharmaceutical interest, equivalent profiles were run on magnetic tape files of CA-Condensates," CBAC," Excerpta Medica," MEDLARS" and Ringdoc." The results are tabulated for overlap of services, relative speed of citing references, and unique…

Toxicology of sulfur in ruminants: review

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

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 sulfurmore » leads to toxic effects. 53 references, 1 table.« less

Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases.

PubMed

Fineschi, V; Centini, F; Mazzeo, E; Turillazzi, E

1999-09-30

Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post-mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response.

RFC 18001 – Anthraquinone – Supplemental Information

EPA Pesticide Factsheets

RFC 18001 – Anthraquinone – Supplemental Information demonstrating that National Toxicology Program Technical Report 494 should not be the basis for provisional screening values presented in Appendix A of “Provisional Peer-Reviewed Toxicity Values

Nitrobenzodiazepines: Postmortem brain and blood reference concentrations.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Linnet, Kristian

2016-11-01

Reference concentrations are needed to evaluate postmortem toxicology results and usually femoral blood is the specimen of choice. However, brain tissue has been suggested as a viable alternative specimen, since postmortem blood concentrations can be difficult to interpret due to postmortem redistribution, among other factors. Here we present reference concentrations of postmortem brain and femoral blood of the nitrobenzodiazepines clonazepam, flunitrazepam, and nitrazepam that are of particular interest since they commonly are converted to their corresponding 7-aminometabolites in the postmortem situation. The drugs and metabolites were quantified in both matrices using LC-MS-MS in 69 cases. In 63 cases the compounds were judged not to have been of significance for the death (C cases), whereas they were considered to have been a contributing factor in 6 cases (B cases). No cases were observed with a nitrobenzodiazepine being the sole cause of death (A cases). The brain-blood ratios for clonazepam and nitrazepam were 5.5 and 4.7, respectively, while the brain-blood ratios for the 7-aminometabolites ranged from 0.4 to 0.5. Flunitrazepam only occurred as the 7-aminometabolite. A positive correlation between brain and blood concentrations was found with Spearman's rank correlation coefficients (r s ) ranging from 0.77 to 0.96. The measured femoral blood concentrations agree with literature values, but only few brain concentrations were available for comparison. The drug-metabolite ratios for clonazepam and nitrazepam were 10-12 times higher in brain than in blood. The pre-analytical variation in brain of 5.9% was fairly low, suggesting that brain tissue is a useful alternative to blood. The reported brain and femoral blood concentrations serve as reference values in postmortem investigations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multivariate analysis of toxicity experimental results of environmental endpoints. (FutureToxII)

EPA Science Inventory

The toxicity of hundreds of chemicals have been assessed in laboratory animal studies through EPA chemical regulation and toxicological research. Currently, over 5000 laboratory animal toxicity studies have been collected in the Toxicity Reference Database (ToxRefDB). In addition...

The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and applications

EPA Science Inventory

Historically, risk assessment has relied upon toxicological data to obtain hazard-based reference levels, which are subsequently compared to exposure estimates to determine whether an unacceptable risk to public health may exist. Recent advances in analytical methods, biomarker ...

IRIS TOXICOLOGICAL REVIEW OF DECABROMODIPHENYL ETHER (EXTERNAL REVIEW DRAFT)

EPA Science Inventory

The U.S. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessments of congeners of polybrominated diphenyl ethers (PDBEs), this review is about Decabromodiphenyl Ether, or commonly referred to as decaBDE (BDE-209). ...

Characterization of the rainbow trout transcriptome using Sanger and 454-Pyrosequencing approaches

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Rainbow trout is an important fish species for aquaculture and a model species for research investigations associated with carcinogenesis, comparative immunology, toxicology and the evolutionary biology. However, to date there is no genome reference sequence to facilitate the development...

Status of the rainbow trout genome reference sequence assembly

USDA-ARS?s Scientific Manuscript database

Rainbow trout (Oncorhynchus mykiss) are the most cultivated cold water fish in the U.S. In addition to interests associated with aquaculture and sport fisheries, the rainbow trout serves as a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ...

Characterization of the rainbow trout transcriptome using Sanger and 454-pyrosequencing approaches

USDA-ARS?s Scientific Manuscript database

Background: Rainbow trout is an important fish for aquaculture and recreational fisheries and serves as a model species for research investigations associated with carcinogenesis, comparative immunology, toxicology and the evolutionary biology. However, to date there is no genome reference sequence...

Uses of available record systems in epidemiologic studies of reproductive toxicology

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

Polednak, A.P.; Janerich, D.T.

The uses of available record systems in epidemiologic studies of reproductive toxicology are described with reference to New York State. The available record systems (and relevant reproductive end points) described include: a newborn screening program for metabolic diseases and hemoglobinopathies (relevant to point mutations); chromosome registries and prenatal cytogenetics (for chromosome anomalies); live birth certificates (for birth defects, birthweight, sex ratio, etc); fetal death certificates (for spontaneous fetal deaths); and a statewide cancer registry (for childhood cancers and transplacental carcinogenesis). The uses and limitations of these record systems are discussed, along with examples of their use in descriptive and analyticmore » epidemiologic studies. Descriptive studies outlined include investigations of temporal and geographic trends in birth defects, birth weight, and fetal deaths, with reference to environmental questions (eg, Love Canal, nuclear power plants). Analytic studies described concern parental occupation in relation to specific birth defects (neural tube defects and Down syndrome) and maternal use of contraceptive drugs.« less

Handbook of ecotoxicology

USGS Publications Warehouse

Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

1995-01-01

The Handbook of Ecotoxicology offers 34 chapters with contributions from over 50 selected international experts. The book is divided into four major sections: I. Quantifying and Measuring Ecotoxicological Effects, II. Contaminant Sources and Effects, III. Case Histories and Ecosystem Surveys, and IV. Methods for Making Estimates and Predictability in Ecotoxicology. Concepts and methodology are presented for many types of aquatic and terrestrial ecotoxicity test protocols for both controlled and field assessments. Chapters are offered on such diverse topics as sediment and soil ecotoxicity, landscape indicators, biomonitoring, and use of current bioindicators. The roles of deforestation and global warming, pathogens and disease in ecotoxicology, abiotic factors, urban runoff, predictive ecotoxicology, population modeling, and restoration ecology are discussed. This book was designed to serve as a reference book for students entering the fields of ecotoxicology, aquatic toxicology, terrestrial wildlife toxicology, and other environmental sciences. Many portions of this handbook will serve as a convenient reference text for established investigators, resource managers, and those involved in risk assessment and risk management within regulatory agencies and the private sector.

A Harmonized Physiologically Based Pharmacokinetic Model for Nonane as a Component of Jet Fuel

DTIC Science & Technology

2007-09-16

96-C-9010). Lt Col Terry A. Childress served as Contract Officer Representative for the U.S. Air Force, Armstrong Laboratory, Toxicology Division...fibers and solvents. These values are being used by Dr. Subhash Basak (University of Minnesota, personal communication) for 44 hierarchical QSAR ...that they exist individually at very low concentrations, and they are of no particular toxicological concern in themselves. It is not worth

Occurrences and toxicological risk assessment of eight heavy metals in agricultural soils from Kenya, Eastern Africa.

PubMed

Mungai, Teresiah Muciku; Owino, Anita Awino; Makokha, Victorine Anyango; Gao, Yan; Yan, Xue; Wang, Jun

2016-09-01

The concentration distribution and toxicological assessment of eight heavy metals including lead (Pb), cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), mercury (Hg), arsenic (As), and zinc (Zn) in agricultural soils from Kenya, Eastern Africa, were investigated in this study. The results showed mean concentrations of eight heavy metals of Zn, Pb, Cr, Cu, As, Ni, Hg, and Cd in agricultural soils as 247.39, 26.87, 59.69, 88.59, 8.93, 12.56, 8.06, and 0.42 mg kg(-1), respectively. These mean values of eight heavy metals were close to the toxicity threshold limit of USEPA standard values of agricultural soils, indicating potential toxicological risk to the food chain. Pollution index values revealed that eight heavy metals severely decreased in the order Hg > Cd > As > Cu > Pb > Zn > Ni > Cr and the mean value of the overall pollution index of Hg and Cd was 20.31, indicating severe agriculture ecological risk. Potential pollution sources of eight heavy metals in agricultural soils were mainly from anthropogenic activities and natural dissolution. The intensification of human agricultural activities, the growing industrialization, and the rapid urbanization largely influenced the concentration levels of heavy metals in Kenya, Eastern Africa. Moreover, the lack of agricultural normalization management and poor enforcement of environmental laws and regulations further intensified the widespread pollution of agricultural soils in Kenya.

Simultaneous LC-MS/MS determination of JWH-210, RCS-4, ∆(9)-tetrahydrocannabinol, and their main metabolites in pig and human serum, whole blood, and urine for comparing pharmacokinetic data.

PubMed

Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Peters, Benjamin; Bregel, Dietmar; Menger, Michael D; Maurer, Hans H; Ewald, Andreas H; Schmidt, Peter H

2015-05-01

A series of new synthetic cannabinoids (SC) has been consumed without any toxicological testing. For example, pharmacokinetic data have to be collected from forensic toxicological case work and/or animal studies. To develop a corresponding model for assessing such data, samples of controlled pig studies with two selected SC (JWH-210, RCS-4) and, as reference, ∆(9)-tetrahydrocannabinol (THC) should be analyzed as well as those of human cases. Therefore, a method for determination of JWH-210, RCS-4, THC, and their main metabolites in pig and human serum, whole blood, and urine samples is presented. Specimens were analyzed by liquid-chromatography tandem mass spectrometry and multiple-reaction monitoring with three transitions per compound. Full validation was carried out for the pig specimens and cross-validation for the human specimens concerning precision and bias. For the pig studies, the limits of detection were between 0.05 and 0.50 ng/mL in serum and whole blood and between 0.05 and 1.0 ng/mL in urine, the lower limits of quantification between 0.25 and 1.0 ng/mL in serum and 0.50 and 2.0 ng/mL in whole blood and urine, and the intra- and interday precision values lower than 15% and bias values within ±15%. The applicability was tested with samples taken from a pharmacokinetic pilot study with pigs following intravenous administration of a mixture of 200 μg/kg body mass dose each of JWH-210, RCS-4, and THC. The cross-validation data for human serum, whole blood, and urine showed that this approach should also be suitable for human specimens, e.g., of clinical or forensic cases.

Chapter 5: Surface water quality sampling in streams and canals

USDA-ARS?s Scientific Manuscript database

Surface water sampling and water quality assessments have greatly evolved in the United States since the 1970s establishment of the Clean Water Act. Traditionally, water quality referred to only the chemical characteristics of the water and its toxicological properties related to drinking water or ...

Use of short-term toxicity data for prediction of long-term health effects

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

Hartley, W.R.; Ohanian, E.V.

1988-01-01

Under the Safe Drinking Water Act Amendments of 1986, the US Environmental Protection Agency determines Maximum Contaminant Level Goals (MCLGs) and enforceable Maximum Contaminant Levels (MCLs) or provides lifetime health advisories (HAs) in the absence of regulatory standards. The critical value for calculation of the lifetime level is the reference dose (RfD). The RfD is an estimate of a lifetime dose which is likely to be without significant risk to human populations. The RfD is determined by dividing the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL) by an uncertainty factor (UF). The NOAEL or LOAEL is determined from toxicologicalmore » or epidemiological studies. For many chemicals, human toxicological or epidemiological data are not available. Chronic mammalian studies are sometimes unavailable. Faced with the need for providing guidance for the increasing number of chemicals threatening our drinking water sources, this paper considers the possibility of providing provisional RfDs using data from toxicological studies of less than ninety days duration. The current UF approach is reviewed along with some proposed mathematical models for extrapolation of NOAELs from dose-response data. The current UF approach to developing the RfD is protective and conservative. More research is needed on the relationship of short- and long-term toxicity data to improve our current approach.« less

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

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

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 thanmore » 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, osprey) (scientific names for both the mammalian and avian species are presented in Appendix B). [In this document, NOAEL refers to both dose (mg contaminant per kg animal body weight per day) and concentration (mg contaminant per kg of food or L of drinking water)]. The 20 wildlife species were chosen because they are widely distributed and provide a representative range of body sizes and diets. The chemicals are some of those that occur at U.S. Department of Energy (DOE) waste sites. The NOAEL-based benchmarks presented in this report represent values believed to be nonhazardous for the listed wildlife species; LOAEL-based benchmarks represent threshold levels at which adverse effects are likely to become evident. These benchmarks consider contaminant exposure through oral ingestion of contaminated media only. Exposure through inhalation and/or direct dermal exposure are not considered in this report.« less

Bibliometrics for Social Validation.

PubMed

Hicks, Daniel J

2016-01-01

This paper introduces a bibliometric, citation network-based method for assessing the social validation of novel research, and applies this method to the development of high-throughput toxicology research at the US Environmental Protection Agency. Social validation refers to the acceptance of novel research methods by a relevant scientific community; it is formally independent of the technical validation of methods, and is frequently studied in history, philosophy, and social studies of science using qualitative methods. The quantitative methods introduced here find that high-throughput toxicology methods are spread throughout a large and well-connected research community, which suggests high social validation. Further assessment of social validation involving mixed qualitative and quantitative methods are discussed in the conclusion.

Bibliometrics for Social Validation

PubMed Central

2016-01-01

This paper introduces a bibliometric, citation network-based method for assessing the social validation of novel research, and applies this method to the development of high-throughput toxicology research at the US Environmental Protection Agency. Social validation refers to the acceptance of novel research methods by a relevant scientific community; it is formally independent of the technical validation of methods, and is frequently studied in history, philosophy, and social studies of science using qualitative methods. The quantitative methods introduced here find that high-throughput toxicology methods are spread throughout a large and well-connected research community, which suggests high social validation. Further assessment of social validation involving mixed qualitative and quantitative methods are discussed in the conclusion. PMID:28005974

Read-Across in the Hazard Assessment of 2,2-Difluoropropane

EPA Science Inventory

2,2-Difluoropropane (DFP) is a hydrofluorocarbon refrigerant contaminant at Superfund sites, but lacked toxicity values and traditional toxicological data in animals. To provide toxicity values to guide site remediation, alternative methods were used to evaluate the potential tox...

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.

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

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

PubMed Central

Lemus, Ranulfo; Venezia, Carmen F.

2015-01-01

Abstract Tungsten is a relatively rare metal with numerous applications, most notably in machine tools, catalysts, and superalloys. In 2003, tungsten was nominated for study under the National Toxicology Program, and in 2011, it was nominated for human health assessment under the US Environmental Protection Agency's (EPA) Integrated Risk Information System. In 2005, the Agency for Toxic Substances and Disease Registry (ATSDR) issued a toxicological profile for tungsten, identifying several data gaps in the hazard assessment of tungsten. By filling the data gaps identified by the ATSDR, this review serves as an update to the toxicological profile for tungsten and tungsten substances. A PubMed literature search was conducted to identify reports published during the period 2004–2014, in order to gather relevant information related to tungsten toxicity. Additional information was also obtained directly from unpublished studies from within the tungsten industry. A systematic approach to evaluate the quality of data was conducted according to published criteria. This comprehensive review has gathered new toxicokinetic information and summarizes the details of acute and repeated-exposure studies that include reproductive, developmental, neurotoxicological, and immunotoxicological endpoints. Such new evidence involves several relevant studies that must be considered when regulators estimate and propose a tungsten reference or concentration dose. PMID:25695728

SERS as a tool for in vitro toxicology.

PubMed

Fisher, Kate M; McLeish, Jennifer A; Jamieson, Lauren E; Jiang, Jing; Hopgood, James R; McLaughlin, Stephen; Donaldson, Ken; Campbell, Colin J

2016-06-23

Measuring markers of stress such as pH and redox potential are important when studying toxicology in in vitro models because they are markers of oxidative stress, apoptosis and viability. While surface enhanced Raman spectroscopy is ideally suited to the measurement of redox potential and pH in live cells, the time-intensive nature and perceived difficulty in signal analysis and interpretation can be a barrier to its broad uptake by the biological community. In this paper we detail the development of signal processing and analysis algorithms that allow SERS spectra to be automatically processed so that the output of the processing is a pH or redox potential value. By automating signal processing we were able to carry out a comparative evaluation of the toxicology of silver and zinc oxide nanoparticles and correlate our findings with qPCR analysis. The combination of these two analytical techniques sheds light on the differences in toxicology between these two materials from the perspective of oxidative stress.

IRIS Toxicological Review of 2,2',4,4'-Tetrabromodiphenyl Ether (External Review Draft)

EPA Science Inventory

The U.S. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessments of congeners of polybrominated diphenyl ethers (PDBEs), this review is about 2,2',4,4'-Tetrabromodiphenyl Ether, or commonly referred to as tetraBDE ...

Productivity in Toxicity Papers

ERIC Educational Resources Information Center

Montgomery, Ruth Reinke

1973-01-01

Personal bibliographies were obtained through a survey of the members of the Society of Toxicology. A group of 183 members showed a 16 percent increase in document output during 1968-1969 compared to 1960-1967. During 1960-1969, 221 members published or made available 1873 documents containing original toxicity data. (5 references) (Author)

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR TETRACHLOROETHYLENE

EPA Science Inventory

The known toxic effects of perchloroethylene will be summarized, with citations from current scientific literature. The critical effects will be identified, and from this the RfD and RfC and cancer unit risk factors will be derived. The RfD and RfC are reference doses and air c...

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

PubMed Central

2012-01-01

Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated. PMID:22284215

Automatic sorting of toxicological information into the IUCLID (International Uniform Chemical Information Database) endpoint-categories making use of the semantic search engine Go3R.

PubMed

Sauer, Ursula G; Wächter, Thomas; Hareng, Lars; Wareing, Britta; Langsch, Angelika; Zschunke, Matthias; Alvers, Michael R; Landsiedel, Robert

2014-06-01

The knowledge-based search engine Go3R, www.Go3R.org, has been developed to assist scientists from industry and regulatory authorities in collecting comprehensive toxicological information with a special focus on identifying available alternatives to animal testing. The semantic search paradigm of Go3R makes use of expert knowledge on 3Rs methods and regulatory toxicology, laid down in the ontology, a network of concepts, terms, and synonyms, to recognize the contents of documents. Search results are automatically sorted into a dynamic table of contents presented alongside the list of documents retrieved. This table of contents allows the user to quickly filter the set of documents by topics of interest. Documents containing hazard information are automatically assigned to a user interface following the endpoint-specific IUCLID5 categorization scheme required, e.g. for REACH registration dossiers. For this purpose, complex endpoint-specific search queries were compiled and integrated into the search engine (based upon a gold standard of 310 references that had been assigned manually to the different endpoint categories). Go3R sorts 87% of the references concordantly into the respective IUCLID5 categories. Currently, Go3R searches in the 22 million documents available in the PubMed and TOXNET databases. However, it can be customized to search in other databases including in-house databanks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Federal environmental and occupational toxicology regulations and reporting requirements: a practical approach to what the medical toxicologist needs to know, part 1.

PubMed

Schwartz, Michael D; Dell'Aglio, Damon M; Nickle, Richard; Hornsby-Myers, Jennifer

2014-09-01

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regard to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act, the Food, Drug, and Cosmetic Act, and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in-depth discussion of the relevant federal environmental laws and statutes and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist but also serves as a key reference for medical toxicology core content on environmental laws and regulations.

Federal environmental and occupational toxicology regulations and reporting requirements: a practical approach to what the medical toxicologist needs to know, part 2.

PubMed

Schwartz, Michael D; Dell'Aglio, Damon M; Nickle, Richard; Hornsby-Myers, Jennifer

2014-12-01

Toxicologists are often called upon to assist in environmental, industrial, occupational and public health assessments. Accordingly, medical toxicologists may find it prudent to be aware of applicable federal toxicological regulations and reporting requirements and of the roles of relevant federal agencies. These regulations are numerous, complex, and have evolved and expanded over time, making it difficult for toxicologists to sustain a current knowledge base. This article reviews the pertinent federal toxicological reporting requirements with regards to the Toxic Substances Control Act (TSCA), the Atomic Energy Act (AEA), the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the Resource Conservation and Recovery Act (RCRA), the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), the Emergency Planning and Community Right to Know Act (EPCRA), the Occupational Safety and Health Act, the Department of Transportation, and information about the National Response Center. We reference internet-based government resources and offer direct links to applicable websites in an attempt to offer rapid and current sources of practical information. The format of the article is a series of hypothetical scenarios followed by commentary. Discussions of the Safe Drinking Water Act and the Food, Drug, and Cosmetic Act and the Dietary Supplement Health and Education Act are beyond the scope of this paper. For those desiring a more in depth discussion of the relevant federal environmental laws and statutes, and applicable case law, the reader is directed to resources such as the Environmental Law Handbook, the websites of individual laws found at www.epa.gov and the decisions of individual courts of appeal. It is our hope that this article provides not only useful practical information for the practicing toxicologist, but also serves as a key reference for Medical Toxicology core content on environmental laws and regulations.

Creation of a digital slide and tissue microarray resource from a multi-institutional predictive toxicology study in the rat: an initial report from the PredTox group.

PubMed

Mulrane, Laoighse; Rexhepaj, Elton; Smart, Valerie; Callanan, John J; Orhan, Diclehan; Eldem, Türkan; Mally, Angela; Schroeder, Susanne; Meyer, Kirstin; Wendt, Maria; O'Shea, Donal; Gallagher, William M

2008-08-01

The widespread use of digital slides has only recently come to the fore with the development of high-throughput scanners and high performance viewing software. This development, along with the optimisation of compression standards and image transfer techniques, has allowed the technology to be used in wide reaching applications including integration of images into hospital information systems and histopathological training, as well as the development of automated image analysis algorithms for prediction of histological aberrations and quantification of immunohistochemical stains. Here, the use of this technology in the creation of a comprehensive library of images of preclinical toxicological relevance is demonstrated. The images, acquired using the Aperio ScanScope CS and XT slide acquisition systems, form part of the ongoing EU FP6 Integrated Project, Innovative Medicines for Europe (InnoMed). In more detail, PredTox (abbreviation for Predictive Toxicology) is a subproject of InnoMed and comprises a consortium of 15 industrial (13 large pharma, 1 technology provider and 1 SME) and three academic partners. The primary aim of this consortium is to assess the value of combining data generated from 'omics technologies (proteomics, transcriptomics, metabolomics) with the results from more conventional toxicology methods, to facilitate further informed decision making in preclinical safety evaluation. A library of 1709 scanned images was created of full-face sections of liver and kidney tissue specimens from male Wistar rats treated with 16 proprietary and reference compounds of known toxicity; additional biological materials from these treated animals were separately used to create 'omics data, that will ultimately be used to populate an integrated toxicological database. In respect to assessment of the digital slides, a web-enabled digital slide management system, Digital SlideServer (DSS), was employed to enable integration of the digital slide content into the 'omics database and to facilitate remote viewing by pathologists connected with the project. DSS also facilitated manual annotation of digital slides by the pathologists, specifically in relation to marking particular lesions of interest. Tissue microarrays (TMAs) were constructed from the specimens for the purpose of creating a repository of tissue from animals used in the study with a view to later-stage biomarker assessment. As the PredTox consortium itself aims to identify new biomarkers of toxicity, these TMAs will be a valuable means of validation. In summary, a large repository of histological images was created enabling the subsequent pathological analysis of samples through remote viewing and, along with the utilisation of TMA technology, will allow the validation of biomarkers identified by the PredTox consortium. The population of the PredTox database with these digitised images represents the creation of the first toxicological database integrating 'omics and preclinical data with histological images.

In vitro cytotoxicity testing of 30 reference chemicals to predict acute human and animal toxicity

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

Barile, F.A.; Arjun, S.; Borges, L.

1991-03-11

This study was conducted in cooperation with the Scandinavian Society of Cell Toxicology, as part of the Multicenter Evaluation for In Vitro Cytotoxicity (MEIC), and was designed to develop an in vitro model for predicting acute human and animal toxicity. The technique relies on the ability of cultured transformed rat lung epithelial cells (L2) to incorporate radiolabled amino acids into newly synthesized proteins in the absence or presence of increasing doses of the test chemical, during a 24-hr incubation. IC50 values were extrapolated from the dose-response curves after linear regression analysis. Human toxic blood concentrations estimated from rodent LD50 valuesmore » suggest that our experimental IC50's are in close correlation with the former. Validation of the data by the MEIC committee shows that our IC50 values predicted human lethal dosage as efficient as rodent LD50's. It is anticipated that this and related procedures may supplement or replace currently used animal protocols for predicting human toxicity.« less

An Attempt to Compare EMCS with TOXLINE.

ERIC Educational Resources Information Center

Lorent, Jean-Pierre; Schirner, Hedi

1978-01-01

Sixteen queries, performed on the two systems, resulted in 247 unique relevant references from EMCS and 559 from TOXLINE. The overlap varied considerably, from 6 to 50 percent. It is remarkable that TOXLINE, with nine subfiles specially compiled for toxicology, can be supplemented by EMCS, which in the present study delivered 31 percent of all the…

ToxRefDB 2.0: Improvements in Capturing Qualitative and Quantitative Data from in vivo Toxicity Studies (SOT)

EPA Science Inventory

The Toxicity Reference Database (ToxRefDB) is a publicly accessible resource that contains 40+ years of in vivo dose-response toxicological studies. ToxRefDB provides curated in vivo toxicity data for systematic evaluation of a continuously expanding catalog of chemicals, and co...

78 FR 67371 - Draft Report on Carcinogens Monographs for ortho-Toluidine and Pentachlorophenol and By-products...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... Monographs for ortho-Toluidine and Pentachlorophenol and By-products of Its Synthesis; Availability of... and By-products of its Synthesis (hereafter referred to as ``pentachlorophenol''). These documents were prepared by the Office of the Report on Carcinogens (ORoC), Division of the National Toxicology...

Triazolam blood concentrations in forensic cases in Canada.

PubMed

Joynt, B P

1993-01-01

Triazolam has been a controversial drug since its appearance on world markets as a hypnotic more than ten years ago. Whole blood concentrations of triazolam as found in forensic cases are cited in several categories; that is, impaired driving: 17 cases; sexual assault: four cases; death due to drugs: 45 cases; drug-related death (drugs contributed to the death but were not the ultimate cause): 20 cases; drug-involved death (drugs were present but were not felt to be a contributing factor): six cases; miscellaneous: one case. The data was gleaned from a forensic toxicology database designed and used by the Forensic Toxicology Sections of the Royal Canadian Mounted Police (RCMP) laboratories in Canada. Triazolam concentrations from selected references are included for comparison.

The genus Vitex: A review

PubMed Central

Rani, Anita; Sharma, Anupam

2013-01-01

The review includes 161 references on the genus Vitex, and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies, and toxicology of the prominent species of Vitex. Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these, leaves and fruits of V. agnus-castus Linn. (Verbenaceae) has been traditionally used in treatment of women complaints. V. agnus-castus has also been included in herbal remedies, which are in clinical use to regulate the menstrual cycle, reduce premenstrual symptom tension and anxiety, treat some menopausal symptoms as well as to treat hormonally induced acne. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Vitex species has been emphasized with a view to establish their multifarious biological activities and mode of action. PMID:24347927

The genus Vitex: A review.

PubMed

Rani, Anita; Sharma, Anupam

2013-07-01

The review includes 161 references on the genus Vitex, and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies, and toxicology of the prominent species of Vitex. Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these, leaves and fruits of V. agnus-castus Linn. (Verbenaceae) has been traditionally used in treatment of women complaints. V. agnus-castus has also been included in herbal remedies, which are in clinical use to regulate the menstrual cycle, reduce premenstrual symptom tension and anxiety, treat some menopausal symptoms as well as to treat hormonally induced acne. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Vitex species has been emphasized with a view to establish their multifarious biological activities and mode of action.

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

Kienhuis, Anne S., E-mail: anne.kienhuis@rivm.nl; RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen; Netherlands Toxicogenomics Centre

Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is usedmore » to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.« less

[Substance monograph on bisphenol A (BPA) - reference and human biomonitoring (HBM) values for BPA in urine. Opinion of the Human Biomonitoring Commission of the German Federal Environment Agency (UBA)].

PubMed

2012-09-01

Bisphenol A (BPA) is used for the production of polycarbonates and synthetic resins. Many of the items that contain BPA, for example polycarbonate bottles and coated cans, are commodities from which BPA can migrate into food and drinks, resulting in ubiquitous exposure of the population. Numerous animal studies and in vitro tests have shown that BPA acts as an "endocrine disruptor". Because of the still incomplete understanding of the complex and contradictory effects of BPA at doses below the NOAEL, the toxicological significance of recent findings is uncertain. The German HBM Commission takes notice that the risk assessment is currently in flux and that in the EU and other countries precautionary bans on BPA have been introduced. In the light of the extensive and growing body of literature, the Commission does not see itself in a position to resolve this controversy, nor to answer the question of the relevance of observed effects of low BPA doses on human health. The Commission has derived reference values (RV95) and TDI-based HBM I values for total BPA in urine. The RV95 values are 30 μg/l for 3-5 year olds, 15 μg/l for 6-14 year olds, and 7 μg/l for 20-29 year olds. The HBM I value for children is 1.5 mg/l and 2.5 mg/l for adults, respectively. The Commission emphasizes that the HBM values will require immediate adjustment should the current TDI of 0.05 mg/kg bw/day be changed. For the practical application of HBM, the Commission recommends an assessment based on the RV95. Confirmed exceedance of the RV95 by repeat measurements should prompt a search for the possible source(s), following the ALARA principle.

Toxicological relevance of emerging contaminants for drinking water quality.

PubMed

Schriks, Merijn; Heringa, Minne B; van der Kooi, Margaretha M E; de Voogt, Pim; van Wezel, Annemarie P

2010-01-01

The detection of many new compounds in surface water, groundwater and drinking water raises considerable public concern, especially when human health based guideline values are not available it is questioned if detected concentrations affect human health. In an attempt to address this question, we derived provisional drinking water guideline values for a selection of 50 emerging contaminants relevant for drinking water and the water cycle. For only 10 contaminants, statutory guideline values were available. Provisional drinking water guideline values were based upon toxicological literature data. The maximum concentration levels reported in surface waters, groundwater and/or drinking water were compared to the (provisional) guideline values of the contaminants thus obtained, and expressed as Benchmark Quotient (BQ) values. We focused on occurrence data in the downstream parts of the Rhine and Meuse river basins. The results show that for the majority of compounds a substantial margin of safety exists between the maximum concentration in surface water, groundwater and/or drinking water and the (provisional) guideline value. The present assessment therefore supports the conclusion that the majority of the compounds evaluated pose individually no appreciable concern to human health. (c) 2009 Elsevier Ltd. All rights reserved.

THE VALUE OF HOME-BASED COLLECTION OF BIOSPECIMENS IN REPRODUCTIVE EPIDEMIOLOGY

EPA Science Inventory

The Value of Home-Based Collection of Biospecimens in Reproductive Epidemiology
John C. Rockett1, Germaine M. Buck2, Courtney D. Johnson2 and Sally D. Perreault1
1Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Rese...

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

Wassom, John S.; Malling, Heinrich V.; Sankaranarayanan, K.

This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969 this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health. As the mutagenesis field unfolded and expanded, the lexicon changed and new wording appeared to better describe this evolving area of research. The term genetic toxicology was coined and became an important subspecialty ofmore » the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society s main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society s major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Chronicling all events and publications that influenced the development of the mutagenesis and genetic toxicology research area for this article was not possible, but some key happenings that contributed to the field s development have been reviewed. Events that led to the origin of EMS are also presented in celebration of the Society s 40th anniversary. Any historical accounting will have perceived deficiencies. Key people, publications, or events that some readers may feel have had significant impact on development of the subject under review may have been overlooked and left out. We are sure that such will be the case with the appraisal given in this article. However, any oversight or failure to make proper acknowledgment of individuals, events, or the citation of relevant references is unintentional.« less

Safety assessment of mushrooms in dietary supplements by combining analytical data with in silico toxicology evaluation.

PubMed

VanderMolen, Karen M; Little, Jason G; Sica, Vincent P; El-Elimat, Tamam; Raja, Huzefa A; Oberlies, Nicholas H; Baker, Timothy R; Mahony, Catherine

2017-05-01

Despite growing popularity in dietary supplements, many medicinal mushrooms have not been evaluated for their safe human consumption using modern techniques. The multifaceted approach described here relies on five key principles to evaluate the safety of non-culinary fungi for human use: (1) identification by sequencing the nuclear ribosomal internal transcribed spacer (ITS) region (commonly referred to as ITS barcoding), (2) screening an extract of each fungal raw material against a database of known fungal metabolites, (3) comparison of these extracts to those prepared from grocery store-bought culinary mushrooms using UHPLCPDA-ELS-HRMS, (4) review of the toxicological and chemical literature for each fungus, and (5) evaluation of data establishing presence in-market. This weight-of-evidence approach was used to evaluate seven fungal raw materials and determine safe human use for each. Such an approach may provide an effective alternative to conventional toxicological animal studies (or more efficiently identifies when studies are necessary) for the safety assessment of fungal dietary ingredients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mouse bioassay for palytoxin. Specific symptoms and dose-response against dose-death time relationships.

PubMed

Riobó, P; Paz, B; Franco, J M; Vázquez, J A; Murado, M A; Cacho, E

2008-08-01

Nowadays, a variety of protocols are applied to quantitate palytoxin. However, there is not desirable agreement among them, the confidence intervals of the basic toxicological parameters are too wide and the formal descriptions lack the necessary generality to establish comparisons. Currently, the mouse bioassay is the most accepted one to categorize marine toxins and it must constitute the reference for other methods. In the present work, the mouse bioassay for palytoxin is deeply analyzed and carefully described showing the initial symptoms of injected mice which are presented here in the first time. These symptoms clearly differ from the more common marine toxins described up to now. Regarding to the toxicological aspects two considerations are taking into account: (i) the empiric models based in the dose-death time relationships cause serious ambiguities and (ii) the traditional moving average method contains in its regular use any inaccuracy elements. Herein is demonstrated that the logistic equation and the accumulative function of Weibull's distribution (with the modifications proposed) generate satisfactory toxicological descriptions in all the respects.

Slit Lamp-Based Ocular Scoring Systems in Toxicology and Drug Development: A Literature Survey.

PubMed

Eaton, Joshua Seth; Miller, Paul E; Bentley, Ellison; Thomasy, Sara M; Murphy, Christopher J

2017-12-01

To present a survey of the features of published slit lamp-based scoring systems and their applicability in the context of modern ocular toxicology and drug development. References describing original or modified slit lamp-based scoring systems for human or veterinary clinical patients or in investigative or toxicologic research were collected following a comprehensive literature review using textbooks and online publication searches. Each system's indications and features were compiled to facilitate comparison. Literature review identified 138 original or modified scoring systems. Most (48%) were published for evaluation of the ocular surface, 34% for the general anterior segment, and 18% for the lens. Most systems were described for assessment of human patients (50%) and small albino laboratory species such as rabbits (19%), rats (12%), and mice (8%). Systems described for pigmented laboratory species and for larger species such as dogs, cats, pigs, and nonhuman primates (NHPs) were comparatively underrepresented. No systems described a lens scoring scheme specific to the dog, cat, pig, or NHP. Scoring schemes for aqueous and vitreous cells were infrequently described for laboratory species. Many slit lamp-based scoring systems have been published, but the features of each differ and complicate translation of findings between different species. Use and interpretation of any scoring system in toxicology and drug development must be done with awareness of the limitations of the system being used.

Love Canal: environmental and toxicological studies

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

Kim, C.S.

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 nomore » 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.« less

The snake as the symbol of medicine, toxicology and toxinology.

PubMed

Ramoutsaki, I A; Haniotakis, S; Tsatsakis, A M

2000-10-01

We investigated the meaning and the roots of the snake's usage as a symbol of medicine, the medical profession, toxicology and toxinology by examining mythological, archeological data and a variety of texts from the ancient Greek world. The snake figure was associated with Asclepios, the ancient Greek God of medicine, and possessed benevolent properties. It was believed to be able to cure a patient or a wounded person just by touch. The snake is also connected with pharmacology and antisepsis, as snakes possess an antivenom against their own poison. The snake is related to sciences associated with poison and death, such as toxicology and toxinology, and it also implies a metaphysical idea. It is connected with the underworld, not only because it crawls on the ground, but because it can bring death, connecting the upper with the underground world. The ability of the snake to shed its skin has been associated with the circle of life, and the renaissance spirit also, ever since early Hellenic antiquity. Consequently, as a symbol of the modern medical profession, toxicology and toxinology, the snake twisted around a stick or the snake beside a pharmapeutic cup, which also implies the use of medicines or even poison, has its roots in the ancient Mediterranean area as proven by the archeological data combined with literary references. Its benevolent as well as its poisonous properties could be paralleled by the similar properties of medicines.

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

PubMed

Horii, Ikuo

2016-01-01

Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision medicine are to be addressed for the new aspect of efficacy and safety evaluation.

Functional toxicology: tools to advance the future of toxicity testing

PubMed Central

Gaytán, Brandon D.; Vulpe, Chris D.

2014-01-01

The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

NASA Astrophysics Data System (ADS)

Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

2018-03-01

This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

Fire test methodology for aerospace materials. 1: Thermal and smoke toxicological assessments of graphite/bismaleimide and graphite/epoxy systems

NASA Technical Reports Server (NTRS)

Kanakia, M. D.; Switzer, W. G.; Hartzell, G. E.; Kaplan, H. L.

1980-01-01

Both materials possess a high degree of thermal stability, with total heat release values being essentially identical under piloted ignition conditions over a range of 5 to 10 W/sq cm incident heat flux. The graphite/epoxy material had a tendency to auto-ignite at a lower heat flux (about 7 W/sq cm) and produced about 23 percent higher peak heat release rates, approximately 42 percent more carbon monoxide and considerably more smoke than the graphite/bismaleimide under conditions of piloted ignition. Toxicological potencies of smoke produced from the two composites were equivalent for 30 minute exposures. Potencies were also comparable to many common materials, such as wood. There was no evidence for the formation of an "unusual toxicant" nor for any short term post-exposure toxicological effects.

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 237

NASA Technical Reports Server (NTRS)

1982-01-01

A bibliography is given on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 483

NASA Technical Reports Server (NTRS)

1999-01-01

Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Reference dose (RfD): description and use in health risk assessments

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

Barnes, D.G.; Dourson, M.

1988-12-01

For many years the concept of the acceptable daily intake has served the toxicological and regulatory fields quite well. However, as approaches to assessing the health significance of exposures to noncarcinogenic substances receive greater scrutiny, some difficulties with this traditional approach have become more apparent. Consequently, the concept of the reference dose is introduced in order to avoid use of prejudicial terms (e.g., safety and acceptable), to promote greater consistency in the assessment of noncarcinogenic chemicals, and to maintain the functional separation between risk assessment and risk management.

Retrospective Mining of Toxicology Data to Discover Multispecies and Chemical Class Effects: Anemia as a Case Study

EPA Science Inventory

Predictive toxicity models (in vitro to in vivo, QSAR, read-across) rely on large amounts of accurate in vivo data. Here, we analyze the quality of in vivo data from the Toxicity Reference Database (ToxRefDB), using chemical-induced anemia as an example. Considerations include v...

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product.

PubMed

Iskandar, Anita R; Mathis, Carole; Martin, Florian; Leroy, Patrice; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Trivedi, Keyur; Grandolfo, Davide; Cabanski, Maciej; Guedj, Emmanuel; Merg, Celine; Frentzel, Stefan; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

2017-01-01

In vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21st Century - a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impact of 3R4F smoke was substantially greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles.

Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke.

PubMed

Wong, Ee Tsin; Kogel, Ulrike; Veljkovic, Emilija; Martin, Florian; Xiang, Yang; Boue, Stephanie; Vuillaume, Gregory; Leroy, Patrice; Guedj, Emmanuel; Rodrigo, Gregory; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

2016-11-30

The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2.2-exposed groups compared with 3R4F-exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent differential gene expression following 3R4F exposure that was less pronounced in the THS2.2-exposed groups. Molecular network analysis showed that inflammatory processes were the most affected by 3R4F, while the extent of THS2.2 impact was much lower. Most other toxicological endpoints evaluated did not show exposure-related effects. Where findings were observed, the effects were similar in 3R4F- and THS2.2-exposed animals. In summary, toxicological changes observed in the respiratory tract organs of THS2.2 aerosol-exposed rats were much less pronounced than in 3R4F-exposed rats while other toxicological endpoints either showed no exposure-related effects or were comparable to what was observed in the 3R4F-exposed rats. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The Impact of Novel Assessment Methodologies in Toxicology on Green Chemistry and Chemical Alternatives.

PubMed

Rusyn, Ivan; Greene, Nigel

2018-02-01

The field of experimental toxicology is rapidly advancing by incorporating novel techniques and methods that provide a much more granular view into the mechanisms of potential adverse effects of chemical exposures on human health. The data from various in vitro assays and computational models are useful not only for increasing confidence in hazard and risk decisions, but also are enabling better, faster and cheaper assessment of a greater number of compounds, mixtures, and complex products. This is of special value to the field of green chemistry where design of new materials or alternative uses of existing ones is driven, at least in part, by considerations of safety. This article reviews the state of the science and decision-making in scenarios when little to no data may be available to draw conclusions about which choice in green chemistry is "safer." It is clear that there is no "one size fits all" solution and multiple data streams need to be weighed in making a decision. Moreover, the overall level of familiarity of the decision-makers and scientists alike with new assessment methodologies, their validity, value and limitations is evolving. Thus, while the "impact" of the new developments in toxicology on the field of green chemistry is great already, it is premature to conclude that the data from new assessment methodologies have been widely accepted yet. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Determination of monobromobimane derivatives of phenylmercapturic and benzylmercapturic acids in urine by high-performance liquid chromatography and fluorimetry.

PubMed

Buratti, M; Brambilla, G; Fustinoni, S; Pellegrino, O; Pulviremti, S; Colombi, A

2001-02-25

A method was developed for the determination in human urine of S-phenylmercapturic (PMA) and S-benzylmercapturic (BMA) acids, metabolites respectively of benzene and toluene. PMA and BMA were determined, after alkaline hydrolysis, to give respectively thiophenol and benzylmercaptan, and coupling of the thiol-containing compounds with monobromobimane (MB), by reversed-phase HPLC on a diphenyl-silica bonded cartridge (100 x 4.6 mm I.D., 5 microm particle size) with fluorimetric detection. Wavelengths for excitation and emission were 375 and 480 nm, respectively. The recovery of PMA and BMA from spiked urines was >90% in the 10-500 microg/l range; the quantification limits were respectively 1 and 0.5 microg/l; day-to-day precision at 42 microg/l was C.V. <7%. The suitability of the proposed procedure for the biological monitoring of exposure to low-level airborne concentrations of benzene and toluene, was evaluated by analyzing the urinary excretion of PMA and BMA in subjects exposed to different sources of aromatic hydrocarbons, namely occupationally-unexposed referents (non-smokers, n=15; moderate smokers, n=8; mean number of cigarettes smoked per-day=17 cig/day) and non-smoker workers occupationally exposed to toluene in maintenance operations of rotogravure machines (non-smokers, n=17). Among referents, non-smokers showed values of PMA ranging from <1 to 4.6 microg/l and BMA from 1.0 to 10.4 microg/l; in smokers, PMA values ranging from 1.2 to 6.7 microg/l and BMA from 9.3 to 39.9 microg/l, were observed. In occupationally exposed non-smoker subjects, BMA median excretion value (23.6 microg/l) was higher than in non-smoker referents (3.5 microg/l) (P<0.001) and individual BMA values (y, microg/l) were associated and increased with airborne toluene concentration (x, mg/m3) according to the equation y=6.5+0.65x (r=0.69, P<0.01, n=17). The proposed analytical method appears to be a sensitive and specific tool for biological monitoring of low-level exposure to benzene and toluene mixtures in occupational and environmental toxicology laboratory.

Aquatic Rational Threshold Value (RTV) Concepts for Army Environmental Impact Assessment.

DTIC Science & Technology

1979-07-01

rreversible impacts. In aquatic impacts. Examination of the etymology of “ration al systems, bot h the possible cause-effect relationships threshold value...namics, aqueous chemistry . toxicology, a driving function. 30 3’ The shading effects of ripar- and aquatic ecology. In addition , when man ’s use ian

The in vitro toxicology of Swedish snus

PubMed Central

Coggins, Christopher R. E.; Ballantyne, Mark; Curvall, Margareta; Rutqvist, Lars-Erik

2012-01-01

Three commercial brands of Swedish snus (SWS), an experimental SWS, and the 2S3 reference moist snuff were each tested in four in vitro toxicology assays. These assays were: Salmonella reverse mutation, mouse lymphoma, in vitro micronucleus, and cytotoxicity. Water extractions of each of the 5 products were tested using several different concentrations; the experimental SWS was also extracted using dimethyl sulfoxide (DMSO). Extraction procedures were verified by nicotine determinations. Results for SWS in the mutagenicity assays were broadly negative: there were occasional positive responses, but these were effectively at the highest concentration only (concentrations well above those suggested by regulatory guidelines), and were often associated with cytotoxicity. The 2S3 reference was unequivocally positive in one of the three conditions of the micronucleus assay (MNA), at the highest concentration only. Positive controls produced the expected responses in each assay. The SWS data are contrasted with data reported for combusted tobacco in the form of cigarettes, where strongly positive responses have been routinely reported for mutagenicity and cytotoxicity. These negative findings in a laboratory setting concur with the large amount of epidemiological data from Sweden, data showing that SWS are associated with considerably lower carcinogenic potential when compared with cigarettes. PMID:22400986

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

PubMed Central

Judson, Richard S.; Martin, Matthew T.; Egeghy, Peter; Gangwal, Sumit; Reif, David M.; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A.; Richard, Ann M.

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases. PMID:22408426

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

PubMed

Judson, Richard S; Martin, Matthew T; Egeghy, Peter; Gangwal, Sumit; Reif, David M; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A; Richard, Ann M

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

Computational toxicology as implemented by the U.S. EPA: providing high throughput decision support tools for screening and assessing chemical exposure, hazard and risk.

PubMed

Kavlock, Robert; Dix, David

2010-02-01

Computational toxicology is the application of mathematical and computer models to help assess chemical hazards and risks to human health and the environment. Supported by advances in informatics, high-throughput screening (HTS) technologies, and systems biology, the U.S. Environmental Protection Agency EPA is developing robust and flexible computational tools that can be applied to the thousands of chemicals in commerce, and contaminant mixtures found in air, water, and hazardous-waste sites. The Office of Research and Development (ORD) Computational Toxicology Research Program (CTRP) is composed of three main elements. The largest component is the National Center for Computational Toxicology (NCCT), which was established in 2005 to coordinate research on chemical screening and prioritization, informatics, and systems modeling. The second element consists of related activities in the National Health and Environmental Effects Research Laboratory (NHEERL) and the National Exposure Research Laboratory (NERL). The third and final component consists of academic centers working on various aspects of computational toxicology and funded by the U.S. EPA Science to Achieve Results (STAR) program. Together these elements form the key components in the implementation of both the initial strategy, A Framework for a Computational Toxicology Research Program (U.S. EPA, 2003), and the newly released The U.S. Environmental Protection Agency's Strategic Plan for Evaluating the Toxicity of Chemicals (U.S. EPA, 2009a). Key intramural projects of the CTRP include digitizing legacy toxicity testing information toxicity reference database (ToxRefDB), predicting toxicity (ToxCast) and exposure (ExpoCast), and creating virtual liver (v-Liver) and virtual embryo (v-Embryo) systems models. U.S. EPA-funded STAR centers are also providing bioinformatics, computational toxicology data and models, and developmental toxicity data and models. The models and underlying data are being made publicly available through the Aggregated Computational Toxicology Resource (ACToR), the Distributed Structure-Searchable Toxicity (DSSTox) Database Network, and other U.S. EPA websites. While initially focused on improving the hazard identification process, the CTRP is placing increasing emphasis on using high-throughput bioactivity profiling data in systems modeling to support quantitative risk assessments, and in developing complementary higher throughput exposure models. This integrated approach will enable analysis of life-stage susceptibility, and understanding of the exposures, pathways, and key events by which chemicals exert their toxicity in developing systems (e.g., endocrine-related pathways). The CTRP will be a critical component in next-generation risk assessments utilizing quantitative high-throughput data and providing a much higher capacity for assessing chemical toxicity than is currently available.

Crowd-Sourced Verification of Computational Methods and Data in Systems Toxicology: A Case Study with a Heat-Not-Burn Candidate Modified Risk Tobacco Product.

PubMed

Poussin, Carine; Belcastro, Vincenzo; Martin, Florian; Boué, Stéphanie; Peitsch, Manuel C; Hoeng, Julia

2017-04-17

Systems toxicology intends to quantify the effect of toxic molecules in biological systems and unravel their mechanisms of toxicity. The development of advanced computational methods is required for analyzing and integrating high throughput data generated for this purpose as well as for extrapolating predictive toxicological outcomes and risk estimates. To ensure the performance and reliability of the methods and verify conclusions from systems toxicology data analysis, it is important to conduct unbiased evaluations by independent third parties. As a case study, we report here the results of an independent verification of methods and data in systems toxicology by crowdsourcing. The sbv IMPROVER systems toxicology computational challenge aimed to evaluate computational methods for the development of blood-based gene expression signature classification models with the ability to predict smoking exposure status. Participants created/trained models on blood gene expression data sets including smokers/mice exposed to 3R4F (a reference cigarette) or noncurrent smokers/Sham (mice exposed to air). Participants applied their models on unseen data to predict whether subjects classify closer to smoke-exposed or nonsmoke exposed groups. The data sets also included data from subjects that had been exposed to potential modified risk tobacco products (MRTPs) or that had switched to a MRTP after exposure to conventional cigarette smoke. The scoring of anonymized participants' predictions was done using predefined metrics. The top 3 performers' methods predicted class labels with area under the precision recall scores above 0.9. Furthermore, although various computational approaches were used, the crowd's results confirmed our own data analysis outcomes with regards to the classification of MRTP-related samples. Mice exposed directly to a MRTP were classified closer to the Sham group. After switching to a MRTP, the confidence that subjects belonged to the smoke-exposed group decreased significantly. Smoking exposure gene signatures that contributed to the group separation included a core set of genes highly consistent across teams such as AHRR, LRRN3, SASH1, and P2RY6. In conclusion, crowdsourcing constitutes a pertinent approach, in complement to the classical peer review process, to independently and unbiasedly verify computational methods and data for risk assessment using systems toxicology.

Toxicology, occurrence and risk characterisation of the chloropropanols in food: 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol.

PubMed

Andres, Susanne; Appel, Klaus E; Lampen, Alfonso

2013-08-01

Great attention has been paid to chloropropanols like 3-monochloro-1,2-propanediol and the related substance glycidol due to their presence in food and concerns about their toxic potential as carcinogens. The other chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol have been found in certain foods, but occurrence data are generally limited for these compounds. 1,3-dichloro-2-propanol has the most toxicological relevance showing clear carcinogenic effects in rats possibly via a genotoxic mechanism. The dietary exposure to 1,3-dichloro-2-propanol is quite low. Calculated "Margins of Exposure" values are above 10,000. It is concluded that the 1,3-dichloro-2-propanol exposure is of low concern for human health. The toxicology of 2,3-dichloro-1-propanol has not been adequately investigated. Its toxicological potential regarding hepatotoxic effects seems to be lower than that of 1,3-dichloro-2-propanol. Limited data show that 2,3-dichloro-1-propanol occurs only in trace amounts in food, indicating that exposure to 2,3-dichloro-1-propanol seems to be also of low concern for human health. The dietary 2-monochloro-1,3-propanediol burden appears to be lower than that of 3-monochloro-1,2-propanediol. An adequate risk assessment for 2-monochloro-1,3-propanediol cannot be performed due to limited data on the toxicology and occurrence in food. This article reviews the relevant information about the toxicology, occurrence and dietary exposure to the chloropropanols 2-monochloro-1,3-propanediol, 1,3-dichloro-2-propanol and 2,3-dichloro-1-propanol. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

EPA Science Inventory

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

The Installation Restoration Program Toxicology Guide. Volume 3

DTIC Science & Technology

1989-07-01

zvli UW OF TABLES Volun.e 4 (Cont.) 69-3 Chemical Additives ............................ 69-15 69-4 Acute Toxicity of Components of Mineral Base...659. Values were estimated by Arthur D. little, Inc. uwing Kow as the basis of estimation (See Introduction, VoL 1). Values of less than one are very...Introduction, Vol. 1). 659. Values were etfiinated by Arthur D. little, In~c. uwing Kow as the basis of. estimation (See Introduction, Vol. 1). Values of

Health effects of toxicants: Online knowledge support

PubMed Central

Judson, Richard; de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva

2016-01-01

Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. PMID:26506572

Health Effects of Toxicants: Online Knowledge Support ...

EPA Pesticide Factsheets

Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. A review of online public data sources and data resources on health effects of toxicants offered by NLM, EPA and OECD..

Health effects of toxicants: Online knowledge support.

PubMed

Wexler, Philip; Judson, Richard; de Marcellus, Sally; de Knecht, Joop; Leinala, Eeva

2016-01-15

Research in toxicology generates vast quantities of data which reside on the Web and are subsequently appropriated and utilized to support further research. This data includes a broad spectrum of information about chemical, biological and radiological agents which can affect health, the nature of the effects, treatment, regulatory measures, and more. Information is structured in a variety of formats, including traditional databases, portals, prediction models, and decision making support tools. Online resources are created and housed by a variety of institutions, including libraries and government agencies. This paper focuses on three such institutions and the tools they offer to the public: the National Library of Medicine (NLM) and its Toxicology and Environmental Health Information Program, the United States Environmental Protection Agency (EPA), and the Organisation for Economic Co-operation and Development (OECD). Reference is also made to other relevant organizations. Published by Elsevier Inc.

Rational design of gold nanoparticle toxicology assays: a question of exposure scenario, dose and experimental setup.

PubMed

Taylor, Ulrike; Rehbock, Christoph; Streich, Carmen; Rath, Detlef; Barcikowski, Stephan

2014-09-01

Many studies have evaluated the toxicity of gold nanoparticles, although reliable predictions based on these results are rare. In order to overcome this problem, this article highlights strategies to improve comparability and standardization of nanotoxicological studies. To this end, it is proposed that we should adapt the nanomaterial to the addressed exposure scenario, using ligand-free nanoparticle references in order to differentiate ligand effects from size effects. Furthermore, surface-weighted particle dosing referenced to the biologically relevant parameter (e.g., cell number or organ mass) is proposed as the gold standard. In addition, it is recommended that we should shift the focus of toxicological experiments from 'live-dead' assays to the assessment of cell function, as this strategy allows observation of bioresponses at lower doses that are more relevant for in vivo scenarios.

Immunotoxicology: fifty years of global scientific progress.

PubMed

McKarns, Susan C; Kerkvliet, Nancy I; Dean, Jack H; Bonn, Michael B; Cohen, Mitchell D; Franko, Jennifer; Laiosa, Michael D; Lawrence, B Paige; Luebke, Robert W; Luster, Michael I; Miller, Patrick G; Palmer, Rachel K; Pfau, Jean C; Raman, Priyadarshini; Regal, Jean F; Rodgers, Kathleen E; Schondelmeyer, Rio S; Zhang, Xiaochu; Burns-Naas, Leigh Ann

2012-01-01

The Immunotoxicology Specialty Section of the Society of Toxicology (SOT) celebrated the 50(th) Anniversary of the SOT by constructing a poster to highlight the milestones of Immunotoxicology during that half-century period. This poster was assembled by an ad hoc committee and intertwines in words, citations, graphics, and photographs our attempts to capture a timeline reference of the development and progressive movement of immunotoxicology across the globe. This poster was displayed during the 50(th) Annual SOT Meeting in Washington DC in March, 2011. The poster can be accessed by any Reader at the SOT Website via the link http://www.toxicology.org/AI/MEET/AM2011/posters_rcsigss.asp#imss. We dedicate this poster to all of the founders and the scientists that followed them who have made the discipline of Immunotoxicology what it is today.

The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.

PubMed

Sahota, Tarjinder; Danhof, Meindert; Della Pasqua, Oscar

2015-06-01

Current toxicity protocols relate measures of systemic exposure (i.e. AUC, Cmax) as obtained by non-compartmental analysis to observed toxicity. A complicating factor in this practice is the potential bias in the estimates defining safe drug exposure. Moreover, it prevents the assessment of variability. The objective of the current investigation was therefore (a) to demonstrate the feasibility of applying nonlinear mixed effects modelling for the evaluation of toxicokinetics and (b) to assess the bias and accuracy in summary measures of systemic exposure for each method. Here, simulation scenarios were evaluated, which mimic toxicology protocols in rodents. To ensure differences in pharmacokinetic properties are accounted for, hypothetical drugs with varying disposition properties were considered. Data analysis was performed using non-compartmental methods and nonlinear mixed effects modelling. Exposure levels were expressed as area under the concentration versus time curve (AUC), peak concentrations (Cmax) and time above a predefined threshold (TAT). Results were then compared with the reference values to assess the bias and precision of parameter estimates. Higher accuracy and precision were observed for model-based estimates (i.e. AUC, Cmax and TAT), irrespective of group or treatment duration, as compared with non-compartmental analysis. Despite the focus of guidelines on establishing safety thresholds for the evaluation of new molecules in humans, current methods neglect uncertainty, lack of precision and bias in parameter estimates. The use of nonlinear mixed effects modelling for the analysis of toxicokinetics provides insight into variability and should be considered for predicting safe exposure in humans.

Age-specific absolute and relative organ weight distributions for B6C3F1 mice.

PubMed

Marino, Dale J

2012-01-01

The B6C3F1 mouse is the standard mouse strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). While numerous reports have been published on growth, survival, and tumor incidence, no overall compilation of organ weight data is available. Importantly, organ weight change is an endpoint used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. Furthermore, physiologically based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from NCI/NTP studies in order to develop age-specific distributions. Results show that organ weights were collected more frequently in NCI/NTP studies at 2-wk (60 studies), 3-mo (147 studies), and 15-mo (40 studies) intervals than at other intervals, and more frequently from feeding and inhalation than drinking water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Results show age-related increases in absolute liver, right kidney, lung, and heart weights and relatively stable brain and right testis weights. The results suggest a general variability trend in absolute organ weights of brain < right testis < right kidney < heart < liver < lung < spleen < thymus. This report describes the results of this effort.

Chemical Characterization and Toxicologic Evaluation of Airborne Mixtures. Tumorigenicity Studies of Diesel Fuel-2, Red Smoke Dye and Violet Smoke Dyes in the SENCAR Mouse Skin Tumorigenesis Bioassay System

DTIC Science & Technology

1985-09-01

11, 4. TITLE (and Subtitle) Chemical Characterization and Toxi - S. TYPE OF REPORT & PERIOD COVERED cologic Evaluation of Airborne Mixtures / Technical...REFERENCES (Cont’d) Nesnow, S., L. L. Triplett, and T. J. Slaga. 1981. Tumorigenesis of diesel exhaust, gasoline exhaust, and related emission

[Renal excretion of total porphyrins and hippuric acid in rats].

PubMed

Gartzke, J; Burck, D

1986-09-01

The amounts of total porphyrins, hippuric acid and creatinine, excreted in urine by adult male Wistar rats, exhibited normal distributions for hippuric acid and creatinine, but a bimodal distribution for total porphyrins. This typical distribution of total porphyrins was still observed when creatinine was used as reference parameter. In biochemical and toxicological experiments in rats, the tested parameters should be therefore be investigated for homogeneity.

Interpreting biomonitoring data for 2,4-dichlorophenoxyacetic acid: Update to Biomonitoring Equivalents and population biomonitoring data.

PubMed

Aylward, L L; Hays, S M

2015-12-01

Urinary biomonitoring data for 2,4-dichlorophenoxyacetic acid (2,4-D) reflect aggregate population exposures to trace 2,4-D residues in diet and the environment. These data can be interpreted in the context of current risk assessments by comparison to a Biomonitoring Equivalent (BE), which is an estimate of the average biomarker concentration consistent with an exposure guidance value such as the US EPA Reference Dose (RfD). BE values are updated here from previous published BE values to reflect a change in the US EPA RfD. The US EPA RfD has been updated to reflect a revised point of departure (POD) based on new information from additional toxicological studies and updated assessment of applicable uncertainty factors. In addition, new biomonitoring data from both the US National Health and Nutrition Examination Survey (NHANES) and the Canadian Health Measures Survey (CHMS) have been published. The updated US EPA chronic RfD of 0.21 mg/kg-d results in updated BE values of 10,500 and 7000 μg/L for adults and children, respectively. Comparison of the current population-representative data to these BE values shows that upper bound population biomarker concentrations are more than 5000-fold below BE values corresponding to the updated US EPA RfD. This biomonitoring-based risk assessment supports the conclusion that current use patterns in the US and Canada result in incidental exposures in the general population that can be considered negligible in the context of the current 2,4-D risk assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

Sensitivity of ecological soil-screening levels for metals to exposure model parameterization and toxicity reference values.

PubMed

Sample, Bradley E; Fairbrother, Anne; Kaiser, Ashley; Law, Sheryl; Adams, Bill

2014-10-01

Ecological soil-screening levels (Eco-SSLs) were developed by the United States Environmental Protection Agency (USEPA) for the purposes of setting conservative soil screening values that can be used to eliminate the need for further ecological assessment for specific analytes at a given site. Ecological soil-screening levels for wildlife represent a simplified dietary exposure model solved in terms of soil concentrations to produce exposure equal to a no-observed-adverse-effect toxicity reference value (TRV). Sensitivity analyses were performed for 6 avian and mammalian model species, and 16 metals/metalloids for which Eco-SSLs have been developed. The relative influence of model parameters was expressed as the absolute value of the range of variation observed in the resulting soil concentration when exposure is equal to the TRV. Rank analysis of variance was used to identify parameters with greatest influence on model output. For both birds and mammals, soil ingestion displayed the broadest overall range (variability), although TRVs consistently had the greatest influence on calculated soil concentrations; bioavailability in food was consistently the least influential parameter, although an important site-specific variable. Relative importance of parameters differed by trophic group. Soil ingestion ranked 2nd for carnivores and herbivores, but was 4th for invertivores. Different patterns were exhibited, depending on which parameter, trophic group, and analyte combination was considered. The approach for TRV selection was also examined in detail, with Cu as the representative analyte. The underlying assumption that generic body-weight-normalized TRVs can be used to derive protective levels for any species is not supported by the data. Whereas the use of site-, species-, and analyte-specific exposure parameters is recommended to reduce variation in exposure estimates (soil protection level), improvement of TRVs is more problematic. © 2014 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc.

[Toxicological and analytical lists: chromium and its compounds].

PubMed

Minoia, C; Apostoli, P; Battaglia, A; Catenacci, G; Cottica, D; Franco, G; Pozzoli, L; Vanola, C; Candura, F; Capodaglio, E

1987-03-01

The main aspects of occupational exposure to chromium and chromium compounds are surveyed. Special attention is paid to the toxic action of this metal at the different target organs. The nutritional aspect of CrIII is examined preliminarily, and data detailing the metal contents in water and food are provided. As far the different working processes that entail occupational exposure to chromium are concerned, hygienic and environmental problems are discussed while identifying the average environment exposure to the different chemical forms of chromium (CrIII, CrIV, soluble and not soluble), as a function of the worker's tasks, and the relevant human response (total human Cr). Different hygienic and environmental standards in force in various countries and applicable to chromium compounds are compared. Additional information is given on the main aspects of chromium metabolism (absorption, distribution, excretion), and on the prevailing toxic actions, with specific reference to cancerogenesis. As far as biologic monitoring of the exposed people is concerned, the significance of Cr-U as dose-exposure indicator is discussed, also in the light of a critical review of the reference values. The report describes a series of analytical methods for the identification of chromium in aqueous and biologic matrices. The problems connected with health monitoring and fitness for work are eventually covered.

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

The assessment of spray drift damage for ten major crops in Belgium.

PubMed

de Schampheleire, M; Spanoghe, P; Steurbaut, W; Nuyttens, D; Sonck, B

2005-01-01

According to the Council Directive 91/414/EC pesticide damage should be assessed by considering the risk for persons arising from occupational, non-dietary exposure and risk to the environment. In this research an assessment for the pesticide damage by droplet spray drift was set up. The percentages of spray drift were estimated with the Ganzelmeier drift curves and the IMAG drift calculator. Knowing the percentages of drift and the applied doses of pesticide formulations in a given crop, the human and environmental exposures (water and bottom) were predicted. Thereupon risk indices were calculated for water organisms, soil organisms and bystanders. A risk index is the ratio of a predicted exposure to a toxicological reference value and gives an indication of the incidence and the severity of the adverse effects likely to occur. Considering the risk index it is possible to define the minimal width of an unsprayed field margin or "buffer zone" to reduce this risk at an acceptable level.

Polycyclic aromatic hydrocarbon contamination in stormwater detention pond sediments in coastal South Carolina.

PubMed

Weinstein, John E; Crawford, Kevin D; Garner, Thomas R

2010-03-01

The purpose of this study was to characterize the polycyclic aromatic hydrocarbon (PAH) contamination in the sediments of stormwater detention ponds in coastal South Carolina. Levels of the sum of PAH analytes were significantly higher in the sediments of commercial ponds compared to that of reference, golf course, low-density residential, and high-density residential ponds. Isomer ratio analysis suggested that the predominant source of PAHs were pyrogenic; however, many ponds had a PAH signature consistent with mixed uncombusted and combusted PAH sources. PAH levels in these sediments could be modeled using both pond drainage area and pond surface area. These results demonstrate that the sediment from most commercial ponds, and a few residential and golf course ponds, were moderately contaminated with PAHs. PAH levels in these contaminated ponds exceeded between 42% and 75% of the ecological screening values for individual PAH analytes established by US EPA Region IV, suggesting that they may pose a toxicological risk to wildlife.

A new four-step hierarchy method for combined assessment of groundwater quality and pollution.

PubMed

Zhu, Henghua; Ren, Xiaohua; Liu, Zhizheng

2017-12-28

A new four-step hierarchy method was constructed and applied to evaluate the groundwater quality and pollution of the Dagujia River Basin. The assessment index system is divided into four types: field test indices, common inorganic chemical indices, inorganic toxicology indices, and trace organic indices. Background values of common inorganic chemical indices and inorganic toxicology indices were estimated with the cumulative-probability curve method, and the results showed that the background values of Mg 2+ (51.1 mg L -1 ), total hardness (TH) (509.4 mg L -1 ), and NO 3 - (182.4 mg L -1 ) are all higher than the corresponding grade III values of Quality Standard for Groundwater, indicating that they were poor indicators and therefore were not included in the groundwater quality assessment. The quality assessment results displayed that the field test indices were mainly classified as grade II, accounting for 60.87% of wells sampled. The indices of common inorganic chemical and inorganic toxicology were both mostly in the range of grade III, whereas the trace organic indices were predominantly classified as grade I. The variabilities and excess ratios of the indices were also calculated and evaluated. Spatial distributions showed that the groundwater with poor quality indices was mainly located in the northeast of the basin, which was well-connected with seawater intrusion. Additionally, the pollution assessment revealed that groundwater in well 44 was classified as "moderately polluted," wells 5 and 8 were "lightly polluted," and other wells were classified as "unpolluted."

Trace element reference values in tissues from inhabitants of the European Community. III. The control of preanalytical factors in the biomonitoring of trace elements in biological fluids.

PubMed

Minoia, C; Pietra, R; Sabbioni, E; Ronchi, A; Gatti, A; Cavalleri, A; Manzo, L

1992-06-09

In the context of a programme concerning the determination of trace elements in body fluids and tissues to establish trace element reference values, research has been undertaken on the control of preanalytical factors in order to develop sufficiently accurate and precise guidelines to be applied in routine work by using techniques such as graphite furnace atomic absorption spectroscopy (GFAAS). Aspects investigated are related to the risk of contamination during blood collection and the use of anticoagulants; the risk of losses during storage and freeze-drying as well as the possible risk of contamination arising from trace elements in airborne particulates of the laboratory environment. For the analysis of Al, Ba, Cd, Co, Cr, Mn, Mo, Ni, Sb, W, V and Zn in blood, Teflon cannula is the method of choice. The anticoagulants do not introduce disturbing contaminations of Rb, Se, Zn, while contaminations were observed for Co, Cr, Mn. Radiotracers in 'metabolized form' (radiolabelled rat or rabbit tissues from animals administered with radioisotopes) show that samples stored for 1 month at -20 degrees C have no significant trace metal losses. Strict ambient air quality standard has to be respected (continuous monitoring) due to the possibility of element contaminations inside the laboratory. The use of matrix modifiers could represent a toxicological risk to the operators. Critical factors should be considered ('metal sheets') for each element in each matrix. For instance 27 factors for Cr in serum have been suggested.

Sex-specific reference intervals of hematologic and biochemical analytes in Sprague-Dawley rats using the nonparametric rank percentile method.

PubMed

He, Qili; Su, Guoming; Liu, Keliang; Zhang, Fangcheng; Jiang, Yong; Gao, Jun; Liu, Lida; Jiang, Zhongren; Jin, Minwu; Xie, Huiping

2017-01-01

Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes. Reference intervals as presently defined for these analytes in Sprague-Dawley rats have not used internationally recommended statistical method nor stratified by sex. Thus, we aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline. Hematology and biochemistry blood samples were collected from 500 healthy Sprague-Dawley rats (250 males and 250 females) in the control groups. We measured 24 hematologic analytes with the Sysmex XT-2100i analyzer, 9 biochemical analytes with the Olympus AU400 analyzer. We then determined statistically relevant sex partitions and calculated reference intervals, including corresponding 90% confidence intervals, using nonparametric rank percentile method. We observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex. Males had higher hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, neutrophils, lymphocytes, monocytes, percentage of neutrophils, percentage of monocytes, alanine aminotransferase, aspartate aminotransferase, and triglycerides compared to females. Females had higher mean corpuscular hemoglobin concentration, plateletcrit, platelet count, eosinophils, percentage of lymphocytes, percentage of eosinophils, creatinine, glucose, total cholesterol and urea compared to males. Sex partition was required for most hematologic and biochemical analytes in Sprague-Dawley rats. We established sex-specific reference intervals, including corresponding 90% confidence intervals, for Sprague-Dawley rats. Understanding the significant discrepancies in hematologic and biochemical analytes between male and female Sprague-Dawley rats provides important insight into physiological effects in test rats. Establishment of locally sex-specific reference intervals allows a more precise evaluation of animal quality and experimental results of Sprague-Dawley rats in our toxicology safety assessment.

Complementary roles for toxicologic pathology and mathematics in toxicogenomics, with special reference to data interpretation and oscillatory dynamics.

PubMed

Morgan, Kevin T; Pino, Michael; Crosby, Lynn M; Wang, Min; Elston, Timothy C; Jayyosi, Zaid; Bonnefoi, Marc; Boorman, Gary

2004-01-01

Toxicogenomics is an emerging multidisciplinary science that will profoundly impact the practice of toxicology. New generations of biologists, using evolving toxicogenomics tools, will generate massive data sets in need of interpretation. Mathematical tools are necessary to cluster and otherwise find meaningful structure in such data. The linking of this structure to gene functions and disease processes, and finally the generation of useful data interpretation remains a significant challenge. The training and background of pathologists make them ideally suited to contribute to the field of toxicogenomics, from experimental design to data interpretation. Toxicologic pathology, a discipline based on pattern recognition, requires familiarity with the dynamics of disease processes and interactions between organs, tissues, and cell populations. Optimal involvement of toxicologic pathologists in toxicogenomics requires that they communicate effectively with the many other scientists critical for the effective application of this complex discipline to societal problems. As noted by Petricoin III et al (Nature Genetics 32, 474-479, 2002), cooperation among regulators, sponsors and experts will be essential for realizing the potential of microarrays for public health. Following a brief introduction to the role of mathematics in toxicogenomics, "data interpretation" from the perspective of a pathologist is briefly discussed. Based on oscillatory behavior in the liver, the importance of an understanding of mathematics is addressed, and an approach to learning mathematics "later in life" is provided. An understanding of pathology by mathematicians involved in toxicogenomics is equally critical, as both mathematics and pathology are essential for transforming toxicogenomics data sets into useful knowledge.

Aerospace toxicology overview: aerial application and cabin air quality.

PubMed

Chaturvedi, Arvind K

2011-01-01

Aerospace toxicology is a rather recent development and is closely related to aerospace medicine. Aerospace toxicology can be defined as a field of study designed to address the adverse effects of medications, chemicals, and contaminants on humans who fly within or outside the atmosphere in aviation or on space flights. The environment extending above and beyond the surface of the Earth is referred to as aerospace. The term aviation is frequently used interchangeably with aerospace. The focus of the literature review performed to prepare this paper was on aerospace toxicology-related subject matters, aerial application and aircraft cabin air quality. Among the important topics addressed are the following: · Aerial applications of agricultural chemicals, pesticidal toxicity, and exposures to aerially applied mixtures of chemicals and their associated formulating solvents/surfactants The safety of aerially encountered chemicals and the bioanalytical methods used to monitor exposures to some of them · The presence of fumes and smoke, as well as other contaminants that may generally be present in aircraft/space vehicle cabin air · And importantly, the toxic effects of aerially encountered contaminants, with emphasis on the degradation products of oils, fluids, and lubricants used in aircraft, and finally · Analytical methods used for monitoring human exposure to CO and HCN are addressed in the review, as are the signs and symptoms associated with exposures to these combustion gases. Although many agricultural chemical monitoring studies have been published, few have dealt with the occurrence of such chemicals in aircraft cabin air. However, agricultural chemicals do appear in cabin air; indeed, attempts have been made to establish maximum allowable concentrations for several of the more potentially toxic ones that are found in aircraft cabin air. In this article, I emphasize the need for precautionary measures to be taken to minimize exposures to aerially encountered chemicals, or aircraft cabin air contaminants and point out the need for future research to better address toxicological evaluation of aircraft-engine oil additives.

An investigation of normal urine with a creatinine concentration under the cutoff of 20 mg/dL for specimen validity testing in a toxicology laboratory.

PubMed

Holden, Brad; Guice, Erica A

2014-05-01

In clinical and forensic toxicology laboratories, one commonly used method for urine specimen validity testing is creatinine concentration. In this study, workplace guidelines are examined to determine their relevance to forensic and clinical toxicology samples. Specifically, it investigates the occurrence of urine creatinine concentrations under 20 mg/dL and notes potential issues with factors influencing creatinine concentration by utilizing a simple, novel method consisting of cation-paring high-pressure liquid chromatography in tandem with ultraviolet detection to determine the creatinine concentration in 3019 donors. Of the 4227 sample population in this study, 209 (4.94%) were below the cutoff value of 20 mg/dL for dilute urine. Because there are many factors that can influence the urinary creatinine concentration, samples that have creatinine under the 20 mg/dL cutoff do not always implicate sample adulteration. © 2014 American Academy of Forensic Sciences.

QSAR Methods.

PubMed

Gini, Giuseppina

2016-01-01

In this chapter, we introduce the basis of computational chemistry and discuss how computational methods have been extended to some biological properties and toxicology, in particular. Since about 20 years, chemical experimentation is more and more replaced by modeling and virtual experimentation, using a large core of mathematics, chemistry, physics, and algorithms. Then we see how animal experiments, aimed at providing a standardized result about a biological property, can be mimicked by new in silico methods. Our emphasis here is on toxicology and on predicting properties through chemical structures. Two main streams of such models are available: models that consider the whole molecular structure to predict a value, namely QSAR (Quantitative Structure Activity Relationships), and models that find relevant substructures to predict a class, namely SAR. The term in silico discovery is applied to chemical design, to computational toxicology, and to drug discovery. We discuss how the experimental practice in biological science is moving more and more toward modeling and simulation. Such virtual experiments confirm hypotheses, provide data for regulation, and help in designing new chemicals.

Preventing Drug-Induced Liver Injury: How Useful Are Animal Models?

PubMed

Ballet, François

2015-01-01

Drug-induced liver injury (DILI) is the most common organ toxicity encountered in regulatory animal toxicology studies required prior to the clinical development of new drug candidates. Very few reports have evaluated the value of these studies for predicting DILI in humans. Indeed, compounds inducing liver toxicity in regulatory toxicology studies are not always correlated with a risk of DILI in humans. Conversely, compounds associated with the occurrence of DILI in phase 3 studies or after market release are often tested negative in regulatory toxicology studies. Idiosyncratic DILI is a rare event that is precipitated in an individual by the simultaneous occurrence of several critical factors. These factors may relate to the host (e.g. human leukocyte antigen polymorphism, inflammation), the drug (e.g. reactive metabolites) or the environment (e.g. diet/microbiota). This type of toxicity therefore cannot be detected in conventional animal toxicology studies. Several animal models have recently been proposed for the identification of drugs with the potential to cause idiosyncratic DILI: rats treated with lipopolysaccharide, Sod2(+/-) mice, panels of inbred mouse strains or chimeric mice with humanized livers. These models are not suitable for use in the prospective screening of new drug candidates. Humans therefore constitute the best model for predicting and assessing idiopathic DILI. © 2015 S. Karger AG, Basel.

Nails in Forensic Toxicology: An Update.

PubMed

Solimini, Renata; Minutillo, Adele; Kyriakou, Chrystalla; Pichini, Simona; Pacifici, Roberta; Busardo, Francesco Paolo

2017-01-01

The analysis of nails as a keratinized matrix to detect drugs or illicit substances has been increasingly used in forensic and clinical toxicology as a complementary test, especially for the specific characteristics of stably accumulating substances for long periods of time. This allows a retrospective investigation of chronic drug abuse, monitoring continuous drug or pharmaceutical use, reveal in utero drug exposure or environmental exposures. We herein review the recent literature investigating drug incorporation mechanisms and drug detection in nails for forensic toxicological purposes. Mechanisms of drug incorporation have not yet been fully elucidated. However, some research has lately contributed to a better understanding of how substances are incorporated into nails, suggesting three potential mechanisms of drug incorporation: contamination from sweat, incorporation from nail bed and incorporation from germinal matrix. In addition, numerous methods dealing with the determination of drugs of abuse, medications and alcohol biomarkers in nails have been reported in studies over the years. The latter methods could find application in clinical and forensic toxicology. The studies herein reviewed point out how important it is to standardize and harmonize the methodologies (either pre-analytical or analytical) for nails analysis and the optimization of sampling as well as the development of proficiency testing programs and the determination of cut-off values. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Automatic miniaturized fluorometric flow system for chemical and toxicological control of glibenclamide.

PubMed

Ribeiro, David S M; Prior, João A V; Taveira, Christian J M; Mendes, José M A F S; Santos, João L M

2011-06-15

In this work, and for the first time, it was developed an automatic and fast screening miniaturized flow system for the toxicological control of glibenclamide in beverages, with application in forensic laboratory investigations, and also, for the chemical control of commercially available pharmaceutical formulations. The automatic system exploited the multipumping flow (MPFS) concept and allowed the implementation of a new glibenclamide determination method based on the fluorometric monitoring of the drug in acidic medium (λ(ex)=301 nm; λ(em)=404 nm), in the presence of an anionic surfactant (SDS), promoting an organized micellar medium to enhance the fluorometric measurements. The developed approach assured good recoveries in the analysis of five spiked alcoholic beverages. Additionally, a good agreement was verified when comparing the results obtained in the determination of glibenclamide in five commercial pharmaceutical formulations by the proposed method and by the pharmacopoeia reference procedure. Copyright © 2011 Elsevier B.V. All rights reserved.

Bioaccumulation and toxicodynamics of cadmium to freshwater planarian and the protective effect of N-acetylcysteine.

PubMed

Wu, Jui-Pin; Chen, Hon-Cheng; Li, Mei-Hui

2012-08-01

Although toxic responses of freshwater planarians after exposure to environmental toxicants can be observed through external toxicological end points, physiological responses inside the bodies of treated planarians have rarely been investigated. The present study was designed, using cadmium (Cd) as a reference toxicant, to determine its bioaccumulation and toxicodynamics in the freshwater planarian, Dugesia japonica, after acute toxicity was obtained. Accumulated Cd concentrations, metallothionein levels, and the oxidative status in planarians were determined after exposure to Cd. Furthermore, we hypothesized that the acute death of Cd-treated planarians was associated with increased oxidative stress. After Cd-treated planarians were coexposed to antioxidant, N-acetylcysteine (NAC), we found that NAC protected planarians from Cd lethality by maintaining the oxidative status and decreasing the bioaccumulation of Cd. The results of the present study support planarians being used as a practical model for toxicological studies of environmental contaminants in the future.

The Threshold of Toxicological Concern for prenatal developmental toxicity in rats and rabbits

PubMed Central

van Ravenzwaay, B.; Jiang, X.; Luechtefeld, T.; Hartung, T.

2018-01-01

The Threshold Toxicological Concern (TTC) is based on the concept that in absence of experimental data reasonable assurance of safety can be given if exposure is sufficiently low. Using the REACH database the low 5th percentile of the NO(A)EL distribution, for prenatal developmental toxicity (OECD guideline 414) was determined. For rats, (434 NO(A)ELs values) for maternal toxicity, this value was 10 mg/kg-bw/day. For developmental toxicity (469 NO(A)ELs): 13 mg/kg-bw/day. For rabbits, (100 NO(A)ELs), the value for maternal toxicity was 4 mg/kg-bw/day, for developmental toxicity, (112 NO(A)EL values): 10 mg/kg-bw/day. The maternal organism may thus be slightly more sensitive than the fetus. Combining REACH- (industrial chemicals) and published BASF-data (mostly agrochemicals), 537 unique compounds with NO(A)EL values for developmental toxicity in rats and 150 in rabbits were evaluated. The low 5th percentile NO(A)EL for developmental toxicity in rats was 10 mg/kg-bw/day and 9.5 mg/kg-bw/day for rabbits. Using an assessment factor of 100, a TTC value for developmental toxicity of 100 µg/kg-bw/day for rats and 95 µg/kg-bw/day for rabbits is calculated. These values could serve as guidance whether or not to perform an animal experiment, if exposure is sufficiently low. In emergency situations this value may be useful for a first tier risk assessment. PMID:28645885

Patterns, trends, and toxicological significance of chlorinated hydrocarbon and mercury contaminants in bald eagle eggs from the Pacific coast of Canada, 1990-1994.

PubMed

Elliott, J E; Norstrom, R J; Smith, G E

1996-10-01

Bald eagle (Haliaeetus leucocephalus) eggs were collected during incubation, 1990-1992, from 16 nests near three bleached-kraft pulp mills, from six nests in the Fraser River estuary and from seven nests at a reference site on the Pacific coast of Canada. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were present in all eggs in a qualitatively similar pattern among sites. Mean concentrations of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) were significantly higher in eggs collected from near three kraft pulp mill sites in the Strait of Georgia (44, 45, 84 ng/kg) than from the reference area in Johnstone Strait (15 ng/kg). There were few differences among sites in mean organochlorine pesticide levels, indicating the diffuse distribution of those chemicals and the domination of atmospheric inputs. Mean concentrations of total polychlorinated biphenyls (PCBs) were highest in eggs from the Strait of Georgia (4.86 mg/kg) and the PCB congener pattern was significantly different between that area and both the lower Fraser valley and Johnstone Strait. Mean mercury concentrations, which were mainly methyl-mercury, were significantly higher in eggs collected from the lower Fraser Valley (0.258 mg/kg) and Johnstone Strait (0.294 mg/kg) compared to the Strait of Georgia (0.188 mg/kg). Individual and regional variation in concentrations of organochlorine pesticides, PCBs and mercury in eagle eggs were thought to be influenced mainly by dietary differences. Toxicologically, in 1990, mean TCDD-toxic equivalents (TEQs) in bald eagle eggs were about two-fold greater than a lowest-observed-effect level, suggested elsewhere for this species, of 210 ng/kg TEQs. In the Strait of Georgia, PCCDs and PCDFs made a greater contribution to TEQs than non-ortho and mono-ortho PCBs, whereas the reverse was true for eggs outside the strait. Mean eggshell thickness was less than the pre-1947 value at all sites, although there was no significant relationship between eggshell thickness and DDE concentrations. Levels of other organochlorine pesticides and mercury were below those considered to be toxic.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 366)

NASA Technical Reports Server (NTRS)

1992-01-01

This bibliography lists 248 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System during Aug. 1992. Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 492

NASA Technical Reports Server (NTRS)

1999-01-01

This report lists reports, articles and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Toward a public toxicogenomics capability for supporting predictive toxicology: survey of current resources and chemical indexing of experiments in GEO and ArrayExpress.

PubMed

Williams-Devane, ClarLynda R; Wolf, Maritja A; Richard, Ann M

2009-06-01

A publicly available toxicogenomics capability for supporting predictive toxicology and meta-analysis depends on availability of gene expression data for chemical treatment scenarios, the ability to locate and aggregate such information by chemical, and broad data coverage within chemical, genomics, and toxicological information domains. This capability also depends on common genomics standards, protocol description, and functional linkages of diverse public Internet data resources. We present a survey of public genomics resources from these vantage points and conclude that, despite progress in many areas, the current state of the majority of public microarray databases is inadequate for supporting these objectives, particularly with regard to chemical indexing. To begin to address these inadequacies, we focus chemical annotation efforts on experimental content contained in the two primary public genomic resources: ArrayExpress and Gene Expression Omnibus. Automated scripts and extensive manual review were employed to transform free-text experiment descriptions into a standardized, chemically indexed inventory of experiments in both resources. These files, which include top-level summary annotations, allow for identification of current chemical-associated experimental content, as well as chemical-exposure-related (or "Treatment") content of greatest potential value to toxicogenomics investigation. With these chemical-index files, it is possible for the first time to assess the breadth and overlap of chemical study space represented in these databases, and to begin to assess the sufficiency of data with shared protocols for chemical similarity inferences. Chemical indexing of public genomics databases is a first important step toward integrating chemical, toxicological and genomics data into predictive toxicology.

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study.

PubMed

Paul Friedman, Katie; Papineni, Sabitha; Marty, M Sue; Yi, Kun Don; Goetz, Amber K; Rasoulpour, Reza J; Kwiatkowski, Pat; Wolf, Douglas C; Blacker, Ann M; Peffer, Richard C

2016-10-01

The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3-5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products' registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information.

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

PubMed Central

Paul Friedman, Katie; Papineni, Sabitha; Marty, M. Sue; Yi, Kun Don; Goetz, Amber K.; Rasoulpour, Reza J.; Kwiatkowski, Pat; Wolf, Douglas C.; Blacker, Ann M.; Peffer, Richard C.

2016-01-01

Abstract The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information. PMID:27347635

Aggregating Data for Computational Toxicology Applications ...

EPA Pesticide Factsheets

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built usi

Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids

PubMed Central

Seely, Kathryn A.; Lapoint, Jeff; Moran, Jeffery H.; Fattore, Liana

2014-01-01

“K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications. PMID:22561602

Opioid overdose mortality in Kansas, 2001-2011: toxicologic evaluation of intent.

PubMed

Okic, Merisa; Cnossen, Leslie; Crifasi, Joseph A; Long, Christopher; Mitchell, Erik K

2013-01-01

Drug concentration is a factor in the determination of the manner of death, but considerable overlap exists between therapeutic and toxic concentrations. This study aims to quantify opioid mortality in Kansas from use of fentanyl, methadone and oxycodone and to evaluate utility of drug concentrations for the determination of the manner of death. Cases referred to a forensic pathology practice in Kansas for autopsy from 1 January 2001 to 31 December 2011 were considered. The criterion for inclusion was detection of fentanyl, methadone and/or oxycodone in postmortem toxicology. Of 9,789 cases, 3,315 had positive toxicology: 180 of fentanyl, 299 of methadone and 310 of oxycodone. There were 207 single opioid fatalities, 264 polydrug overdoses and 318 deaths where an opioid was present but not contributory to the mechanism of death. In line with published studies, incidence of opioid overdose deaths increased over the time of the study. Drug concentrations within each cause and manner of death covered broad ranges. Non-natural and natural manners had less overlap than existed within non-natural manners in limited comparisons. This study shows that drug concentration is independent of manner for non-natural deaths and although insufficient to identify intent, can provide a guideline in differentiating non-natural from natural deaths.

Effects of iron oxide contrast agent in combination with various transfection agents during mesenchymal stem cells labelling: An in vitro toxicological evaluation.

PubMed

Mishra, Sushanta Kumar; Khushu, Subash; Gangenahalli, Gurudutta

2018-03-22

The use of iron oxide nanoparticles for different biomedical applications, hold immense promise to develop negative tissue contrast in magnetic resonance imaging (MRI). Previously, we have optimized the labelling of mesenchymal stem cells (MSCs) with iron oxide nanoparticles complexed to different transfection agents like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of relaxation behaviour and its biological expressions. However, there is a distinct need to investigate the biocompatibility and biosafety concerns coupled with its cytotoxicity and genotoxicity. This study was prepared to evaluate the viability of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in MSCs after labelling. Results demonstrated a marginal alteration in toxicological parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis and DNA damage was detected after stem cell labelling. Insignificant depletion of GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after labelling with IO-PLL and Fe-Pro complexes, which later on recovered and normalized to its baseline. This MSCs labelling could provide a reference guideline for toxicological analysis and relaxometry based in vivo MRI detection. Copyright © 2018. Published by Elsevier Ltd.

Innovative Strategies to Develop Chemical Categories Using a Combination of Structural and Toxicological Properties.

PubMed

Batke, Monika; Gütlein, Martin; Partosch, Falko; Gundert-Remy, Ursula; Helma, Christoph; Kramer, Stefan; Maunz, Andreas; Seeland, Madeleine; Bitsch, Annette

2016-01-01

Interest is increasing in the development of non-animal methods for toxicological evaluations. These methods are however, particularly challenging for complex toxicological endpoints such as repeated dose toxicity. European Legislation, e.g., the European Union's Cosmetic Directive and REACH, demands the use of alternative methods. Frameworks, such as the Read-across Assessment Framework or the Adverse Outcome Pathway Knowledge Base, support the development of these methods. The aim of the project presented in this publication was to develop substance categories for a read-across with complex endpoints of toxicity based on existing databases. The basic conceptual approach was to combine structural similarity with shared mechanisms of action. Substances with similar chemical structure and toxicological profile form candidate categories suitable for read-across. We combined two databases on repeated dose toxicity, RepDose database, and ELINCS database to form a common database for the identification of categories. The resulting database contained physicochemical, structural, and toxicological data, which were refined and curated for cluster analyses. We applied the Predictive Clustering Tree (PCT) approach for clustering chemicals based on structural and on toxicological information to detect groups of chemicals with similar toxic profiles and pathways/mechanisms of toxicity. As many of the experimental toxicity values were not available, this data was imputed by predicting them with a multi-label classification method, prior to clustering. The clustering results were evaluated by assessing chemical and toxicological similarities with the aim of identifying clusters with a concordance between structural information and toxicity profiles/mechanisms. From these chosen clusters, seven were selected for a quantitative read-across, based on a small ratio of NOAEL of the members with the highest and the lowest NOAEL in the cluster (< 5). We discuss the limitations of the approach. Based on this analysis we propose improvements for a follow-up approach, such as incorporation of metabolic information and more detailed mechanistic information. The software enables the user to allocate a substance in a cluster and to use this information for a possible read- across. The clustering tool is provided as a free web service, accessible at http://mlc-reach.informatik.uni-mainz.de.

EPA and EFSA approaches for Benchmark Dose modeling

EPA Science Inventory

Benchmark dose (BMD) modeling has become the preferred approach in the analysis of toxicological dose-response data for the purpose of deriving human health toxicity values. The software packages most often used are Benchmark Dose Software (BMDS, developed by EPA) and PROAST (de...

Using High-Content Imaging to Analyze Toxicological Tipping ...

EPA Pesticide Factsheets

Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points Slide Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points

The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.

PubMed Central

Gold, L S; Manley, N B; Slone, T H; Garfinkel, G B; Rohrbach, L; Ames, B N

1993-01-01

This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long-term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8354183

Brominated flame retardants - Exposure and risk assessment for the general population.

PubMed

Fromme, H; Becher, G; Hilger, B; Völkel, W

2016-01-01

Brominated flame retardants (BFRs) are a large group of different substances used in numerous products to prevent fire hazards. Some of them are persistent in the environment, accumulate in the food chain and are of toxicological concern, while for others current data are limited. Meanwhile, BFRs have been found in many environmental media, foods, and biota including humans. This review presents recent findings obtained from monitoring data in environmental media relevant for human exposure, as well as dietary exposure. In this context, concentrations in indoor and ambient air and in house dust are outlined. Furthermore, we summarize human biomonitoring data on BFR levels in blood and breast milk. Current estimates of the overall exposure of the general population using different relevant subsets are also addressed. All of these data are discussed in relation to currently available toxicological reference values used for risk assessment purposes. Obviously, the exposure of the general population varies considerably in different parts of the world and even within countries. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) show the highest intake during infancy. While the highest intake for BDE 47 for all groups was observed in the US, the total BDE 209 and HBCD intake was highest in the UK. For HBCD and all PBDEs except BDE 209, diet accounts for a large proportion of the total intake during infancy in all countries. With regard to toddlers and adults, the contribution of diet to total intake is high in Germany and the UK, while in the US, the high concentrations of PBDE in dust resulted in a notably smaller proportion of the intake being attributed to diet. Copyright © 2015 Elsevier GmbH. All rights reserved.

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Spacecraft Maximum Allowable Concentrations for Airborne Contaminants

NASA Technical Reports Server (NTRS)

James, John T.

2008-01-01

The enclosed table lists official spacecraft maximum allowable concentrations (SMACs), which are guideline values set by the NASA/JSC Toxicology Group in cooperation with the National Research Council Committee on Toxicology (NRCCOT). These values should not be used for situations other than human space flight without careful consideration of the criteria used to set each value. The SMACs take into account a number of unique factors such as the effect of space-flight stress on human physiology, the uniform good health of the astronauts, and the absence of pregnant or very young individuals. Documentation of the values is given in a 5 volume series of books entitled "Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants" published by the National Academy Press, Washington, D.C. These books can be viewed electronically at http://books.nap.edu/openbook.php?record_id=9786&page=3. Short-term (1 and 24 hour) SMACs are set to manage accidental releases aboard a spacecraft and permit risk of minor, reversible effects such as mild mucosal irritation. In contrast, the long-term SMACs are set to fully protect healthy crewmembers from adverse effects resulting from continuous exposure to specific air pollutants for up to 1000 days. Crewmembers with allergies or unusual sensitivity to trace pollutants may not be afforded complete protection, even when long-term SMACs are not exceeded. Crewmember exposures involve a mixture of contaminants, each at a specific concentration (C(sub n)). These contaminants could interact to elicit symptoms of toxicity even though individual contaminants do not exceed their respective SMACs. The air quality is considered acceptable when the toxicity index (T(sub grp)) for each toxicological group of compounds is less than 1, where T(sub grp), is calculated as follows: T(sub grp) = C(sub 1)/SMAC(sub 1) + C(sub 2/SMAC(sub 2) + ...+C(sub n)/SMAC(sub n).

Assessing the safety of co-exposure to food packaging migrants in food and water using the maximum cumulative ratio and an established decision tree.

PubMed

Price, Paul; Zaleski, Rosemary; Hollnagel, Heli; Ketelslegers, Hans; Han, Xianglu

2014-01-01

Food contact materials can release low levels of multiple chemicals (migrants) into foods and beverages, to which individuals can be exposed through food consumption. This paper investigates the potential for non-carcinogenic effects from exposure to multiple migrants using the Cefic Mixtures Ad hoc Team (MIAT) decision tree. The purpose of the assessment is to demonstrate how the decision tree can be applied to concurrent exposures to multiple migrants using either hazard or structural data on the specific components, i.e. based on the acceptable daily intake (ADI) or the threshold of toxicological concern. The tree was used to assess risks from co-exposure to migrants reported in a study on non-intentionally added substances (NIAS) eluting from food contact-grade plastic and two studies of water bottles: one on organic compounds and the other on ionic forms of various elements. The MIAT decision tree assigns co-exposures to different risk management groups (I, II, IIIA and IIIB) based on the hazard index, and the maximum cumulative ratio (MCR). The predicted co-exposures for all examples fell into Group II (low toxicological concern) and had MCR values of 1.3 and 2.4 (indicating that one or two components drove the majority of the mixture's toxicity). MCR values from the study of inorganic ions (126 mixtures) ranged from 1.1 to 3.8 for glass and from 1.1 to 5.0 for plastic containers. The MCR values indicated that a single compound drove toxicity in 58% of the mixtures. MCR values also declined with increases in the hazard index for the screening assessments of exposure (suggesting fewer substances contributed as risk potential increased). Overall, it can be concluded that the data on co-exposure to migrants evaluated in these case studies are of low toxicological concern and the safety assessment approach described in this paper was shown to be a helpful screening tool.

Repeated-Dose and Reproductive/Developmental Toxicity of NTO (3-Nitro-1,2,4-Triazol-5-One) in the Rat

DTIC Science & Technology

2014-03-21

caused by a parasitic problem or contact dermatitis , the lacerations resolved with topical treatment prior to the skin scrape being performed. Several...14 8 Discussion 16 9 Conclusions 18 10 Point of Contact 19 Appendices A References...postpartum did not indicate that NTO presents a developmental hazard. 18 Toxicology Study No. 85-XC-OFP4-12, April-July 2012 10 Point of Contact

A Gas Chromotographic-Mass Spectrometric Approach to Examining Stereoselective Interaction of Human Plasma Proteins with Soman

DTIC Science & Technology

2008-02-01

ABSTRACT See reprint. 15. SUBJECT TERMS Human plasma proteins, soman, nerve agent , bioscavenger, gas chromatography, mass spectrometry 16. SECURITY...usually referred to as nerve agents ) are tabun (ethyl dimethylamidocyanophosphate, or GA ), sarin (iso- propyl methylfluorophosphonate, or GB), soman...Pharmacology and toxicology of chemical warfare agents Ann. Acad. Med. Singapore 2&: 104-107 (1997). 11. C Macilwain. Study proves Iraq used nerve gas . Nature 3

Hazards posed by a banned drug--phenformin is still hanging around.

PubMed

Ching, C K; Lai, C K; Poon, W T; Wong, Ernest N P; Yan, W W; Chan, Albert Y W; Mak, Tony W L

2008-02-01

The Hospital Authority Toxicology Reference Laboratory confirmed six cases of phenformin use, with or without complications, from July 2005 to November 2006. Two of the patients presented with potentially fatal phenformin-induced lactic acidosis. Phenformin was found (or suspected to be) adulterating Chinese proprietary medicine in five of the six cases. We report these six cases to highlight the underrecognised hazards posed by phenformin, a banned drug in Hong Kong.

USSR and Eastern Europe Scientific Abstracts Biomedical and Behavioral Sciences No. 65.

DTIC Science & Technology

1977-03-01

Biophysics 14 Environmental and Ecological Problems 16 Epidemiology 23 Food Supply 31 Hydrobiology . 32 Immunology 34 Industrial Toxicology 35... productivity was established, as well as a high efficiency of the selection for short stem in .different generations. Figure 1; Tables 6; References 14: 4...on twenty-five sub- jects working in agriculture and handling plant protection products . Measure- ments of the rate of nerve conduction were made on

Hazard identification and risk assessment for biologics targeting the immune system.

PubMed

Weir, Andrea B

2008-01-01

Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed with minimum risks to patients.

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

21 CFR 862.3200 - Clinical toxicology calibrator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Clinical toxicology calibrator. 862.3200 Section... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3200 Clinical toxicology calibrator. (a) Identification. A clinical toxicology calibrator is...

Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

PubMed

Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

2018-03-13

Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of fundamental processes in neural tube formation, brain development and neural specification, aiming at illustrating complexity rather than comprehensiveness. We also give a flavor of the wealth of alternative methods in this area. Given the impressive progress in mechanistic knowledge of human biology and toxicology, the time is right for a conceptual approach for designing testing strategies that cover the integral mechanistic landscape of developmental neurotoxicity. The ontology approach provides a framework for defining this landscape, upon which an integral in silico model for predicting toxicity can be built. It subsequently directs the selection of in vitro assays for rate-limiting events in the biological network, to feed parameter tuning in the model, leading to prediction of the toxicological outcome. Validation of such models requires primary attention to coverage of the biological domain, rather than classical predictive value of individual tests. Proofs of concept for such an approach are already available. The challenge is in mining modern biology, toxicology and chemical information to feed intelligent designs, which will define testing strategies for neurodevelopmental toxicity testing. Copyright © 2018 Elsevier Inc. All rights reserved.

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

21 CFR 862.3280 - Clinical toxicology control material.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Clinical toxicology control material. 862.3280... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3280 Clinical toxicology control material. (a) Identification. A clinical toxicology control...

Toxicity tests aiming to protect Brazilian aquatic systems: current status and implications for management.

PubMed

Martins, Samantha Eslava; Bianchini, Adalto

2011-07-01

The current status of toxicological tests performed with Brazilian native species was evaluated through a survey of the scientific data available in the literature. The information gathered was processed and an electronic toxicology database (http://www.inct-ta.furg.br/bd_toxicologico.php) was generated. This database provides valuable information for researchers to select sensitive and tolerant aquatic species to a large variety of aquatic pollutants. Furthermore, the toxicology database allows researchers to select species representative of an ecosystem of interest. Analysis of the toxicology database showed that ecotoxicological assays have significantly improved in Brazil over the last decade, in spite of the still relatively low number of tests performed and the restricted number of native species tested. This is because most of the research is developed in a few laboratories concentrated in certain regions of Brazil, especially in Southern and Southeast regions. Considering the extremely rich biodiversity and the large variety of aquatic ecosystems in Brazil, this finding points to the urgent need for the development of ecotoxicological studies with other groups of aquatic animals, such as insects, foraminifera, cnidarians, worms, amphibians, among others. This would help to derive more realistic water quality criteria (WQC) values, which would better protect the different aquatic ecosystems in Brazil. Finally, the toxicology database generated presents solid and science based information, which can encourage and drive the Environmental Regulatory Agencies in Brazil to derive WQC based on native species. In this context, the present paper discusses the historical evolution of ecotoxicological studies in Brazil, and how they have contributed to the improvement of the Brazilian Federal and Regional regulations for environment.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 368)

NASA Technical Reports Server (NTRS)

1992-01-01

This bibliography lists 305 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System during Sep. 1992. The subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 486

NASA Technical Reports Server (NTRS)

1999-01-01

In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Create, run, share, publish, and reference your LC-MS, FIA-MS, GC-MS, and NMR data analysis workflows with the Workflow4Metabolomics 3.0 Galaxy online infrastructure for metabolomics.

PubMed

Guitton, Yann; Tremblay-Franco, Marie; Le Corguillé, Gildas; Martin, Jean-François; Pétéra, Mélanie; Roger-Mele, Pierrick; Delabrière, Alexis; Goulitquer, Sophie; Monsoor, Misharl; Duperier, Christophe; Canlet, Cécile; Servien, Rémi; Tardivel, Patrick; Caron, Christophe; Giacomoni, Franck; Thévenot, Etienne A

2017-12-01

Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the multiplicity of bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M; http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Drinking water legislation, pesticides and principles for concern].

PubMed

Dieter, H H

1990-01-01

The limit values prescribed by German drinking water regulations for "pesticides and their toxic main metabolites" (PBSM) protect the consumer from imponderable toxicological risks. It therefore complies with the "principle of concern" which is part of several statutory instruments of the FRG to protect ground and drinking water. Moreover, for about 10% of the permissible active ingredients, health-based limit concentrations in drinking water can be derived which are of the same order of magnitude as the legal limit value for PBSM. The main purpose of the "PBSM Recommendation" of the Federal Health Office of July 1989 is to preserve and to restore a pesticide-free ground and drinking water situation mainly by agricultural measures with at the same time maximum possible health protection for the consumers of drinking water. The bureaucratic handling of this "Recommendation" by the Commission of the EC and the standardised pesticide admittance procedure as envisaged by the EC could seriously endanger this purpose. A consequence would be that, as already in the USA, the same situation could arise in Europe that more and more active ingredients are found in ground water in concentrations which are up to 1,000 fold higher than the respective toxicological limit values for drinking water.

Resource Guide to Careers in Toxicology, 3rd Edition.

ERIC Educational Resources Information Center

Society of Toxicology, Reston, VA.

This resource guide was prepared by the Tox 90's Educational Issues Task Force of the Society of Toxicology. The introduction provides information on the Society of Toxicology and financial support for graduate students in toxicology. Other sections include career opportunities in toxicology, academic and postdoctoral programs in toxicology, and…

Quantitative Assessment of Current Risks to Harlequin Ducks in Prince William Sound, Alaska, from the Exxon Valdez Oil Spill

PubMed Central

Harwell, Mark A.; Gentile, John H.; Parker, Keith R.; Murphy, Stephen M.; Day, Robert H.; Bence, A. Edward; Neff, Jerry M.; Wiens, John A.

2012-01-01

Harlequin Ducks (Histrionicus histrionicus) were adversely affected by the Exxon Valdez oil spill (EVOS) in Prince William Sound (PWS), Alaska, and some have suggested effects continue two decades later. We present an ecological risk assessment evaluating quantitatively whether PWS seaducks continue to be at-risk from polycyclic aromatic hydrocarbons (PAHs) in residual Exxon Valdez oil. Potential pathways for PAH exposures are identified for initially oiled and never-oiled reference sites. Some potential pathways are implausible (e.g., a seaduck excavating subsurface oil residues), whereas other pathways warrant quantification. We used data on PAH concentrations in PWS prey species, sediments, and seawater collected during 2001–2008 to develop a stochastic individual-based model projecting assimilated doses to seaducks. We simulated exposures to 500,000 individuals in each of eight age/gender classes, capturing the variability within a population of seaducks living in PWS. Doses to the maximum-exposed individuals are ∼400–4,000 times lower than chronic toxicity reference values established using USEPA protocols for seaducks. These exposures are so low that no individual-level effects are plausible, even within a simulated population that is orders-of-magnitude larger than exists in PWS. We conclude that toxicological risks to PWS seaducks from residual Exxon Valdez oil two decades later are essentially non-existent. PMID:23723680

Toxicology

NASA Technical Reports Server (NTRS)

Macewen, J. W.

1973-01-01

Oxygen toxicity is examined, including the effects of oxygen partial pressure variations on toxicity and oxygen effects on ozone and nitrogen dioxide toxicity. Toxicity of fuels and oxidizers, such as hydrazines, are reported. Carbon monoxide, spacecraft threshold limit values, emergency exposure limits, spacecraft contaminants, and water quality standards for space missions are briefly summarized.

Sampling the Airway: Improving the Predictive and Toxicological Value of Bronchoalveolar Lavage

EPA Science Inventory

Bronchoalveolar lavage (BAL) is a relatively simple technique to obtain biological material in the form of BAL fluid (BALF) from airways of humans and laboratory animals. Numerous predictive biomarkers of pulmonary injury and diseases can be detected in BALF which aid in diagnosi...

ACToR A Aggregated Computational Toxicology Resource ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

ACToR A Aggregated Computational Toxicology Resource (S) ...

EPA Pesticide Factsheets

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology. We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

QUANTITATIVE TOXICOLOGIC PATHOLOGY-METHODS AND INTERPRETATION' SESSION AT THE JOINT MEETING OF SOCIETY OF TOXICOLOGIC PATHOLOGISTS AND THE INTERNATIONAL FEDERATION OF SOCIETIES OF TOXICOLOGIC PATHOLOGISTS

EPA Science Inventory

Report of the 'Quantitative Toxicologic Pathology - Methods and Interpretation' session at the Joint meeting of Society of Toxicologic Pathologists and the International Federation of Societies of Toxicologic Pathologists, Orlando, Florida, USA, June 24-28, 2001. Douglas C. Wolf,...

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

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

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 citymore » 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.« less

National Toxicology Program: Review of current DHHS, DOE, and EPA research related to toxicology, Fiscal Year 1991

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

Not Available

1991-06-01

The report represents responses by agencies of DHHS, and by DOE and EPA, to requests by the Director of NTP for information on agency programs in basic toxicology research, toxicology testing, and toxicology methods development. Information on dollar and manpower support for agency activities in basic toxicology research, toxicology testing, and toxicology methods development, by DHHS, DOE and EPA, is summarized on pages 4 to 10. All agencies were requested to provide summary information on their programs related to toxicology methods development, whether essential or peripheral to their missions. The information provided in response to the request is summarized inmore » tables on pages 48 to 81. Information was provided on chemical compounds currently being studied for their toxicological properties in intramural laboratories, or on contracts, or through grants.« less

Successful adaption of a forensic toxicological screening workflow employing nontargeted liquid chromatography-tandem mass spectrometry to water analysis.

PubMed

Steger, Julia; Arnhard, Kathrin; Haslacher, Sandra; Geiger, Klemens; Singer, Klaus; Schlapp, Michael; Pitterl, Florian; Oberacher, Herbert

2016-04-01

Forensic toxicology and environmental water analysis share the common interest and responsibility in ensuring comprehensive and reliable confirmation of drugs and pharmaceutical compounds in samples analyzed. Dealing with similar analytes, detection and identification techniques should be exchangeable between scientific disciplines. Herein, we demonstrate the successful adaption of a forensic toxicological screening workflow employing nontargeted LC/MS/MS under data-dependent acquisition control and subsequent database search to water analysis. The main modification involved processing of an increased sample volume with SPE (500 mL vs. 1-10 mL) to reach LODs in the low ng/L range. Tandem mass spectra acquired with a qTOF instrument were submitted to database search. The targeted data mining strategy was found to be sensitive and specific; automated search produced hardly any false results. To demonstrate the applicability of the adapted workflow to complex samples, 14 wastewater effluent samples collected on seven consecutive days at the local wastewater-treatment plant were analyzed. Of the 88,970 fragment ion mass spectra produced, 8.8% of spectra were successfully assigned to one of the 1040 reference compounds included in the database, and this enabled the identification of 51 compounds representing important illegal drugs, members of various pharmaceutical compound classes, and metabolites thereof. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enrichment with Wood Blocks Does Not Affect Toxicity Assessment in an Exploratory Toxicology Model Using Sprague–Dawley Rats

PubMed Central

Ditewig, Amy C; Bratcher, Natalie A; Davila, Donna R; Dayton, Brian D; Ebert, Paige; Lesuisse, Philippe; Liguori, Michael J; Wetter, Jill M; Yang, Hyuna; Buck, Wayne R

2014-01-01

Environmental enrichment in rodents may improve animal well-being but can affect neurologic development, immune system function, and aging. We tested the hypothesis that wood block enrichment affects the interpretation of traditional and transcriptomic endpoints in an exploratory toxicology testing model using a well-characterized reference compound, cyclophosphamide. ANOVA was performed to distinguish effects of wood block enrichment separate from effects of 40 mg/kg cyclophosphamide treatment. Biologically relevant and statistically significant effects of wood block enrichment occurred only for body weight gain. ANOVA demonstrated the expected effects of cyclophosphamide on food consumption, spleen weight, and hematology. According to transcriptomic endpoints, cyclophosphamide induced fewer changes in gene expression in liver than in spleen. Splenic transcriptomic pathways affected by cyclophosphamide included: iron hemostasis; vascular tissue angiotensin system; hepatic stellate cell activation and fibrosis; complement activation; TGFβ-induced hypertrophy and fibrosis; monocytes, macrophages, and atherosclerosis; and platelet activation. Changes in these pathways due to cyclophosphamide treatment were consistent with bone marrow toxicity regardless of enrichment. In a second study, neither enrichment nor type of cage flooring altered body weight or food consumption over a 28-d period after the first week. In conclusion, wood block enrichment did not interfere with a typical exploratory toxicology study; the effects of ingested wood on drug level kinetics may require further consideration. PMID:24827566

Fragrance material review on 16-hydroxy-7-hexadecenoic acid lactone.

PubMed

McGinty, D; Letizia, C S; Api, A M

2011-12-01

A toxicologic and dermatologic review of 16-hydroxy-7-hexadecenoic acid lactone when used as a fragrance ingredient is presented. 16-Hydroxy-7-hexadecenoic acid lactone is a member of the fragrance structural group macrocyclic lactone and lactide derivatives. The fragrance ingredient described herein is one of 12 structurally diverse C14, C15 and C16 compounds that include (1) saturated mono-and (2) saturated di-ester lactones and (3) unsaturated lactones. For the latter, the double bond is not adjacent to (in conjugation with) the ester group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to 16-hydroxy-7-hexadecenoic acid lactone and is not intended as a stand-alone document. Available data were evaluated, then summarized, and include physical properties data. A safety assessment of the entire macrocyclic lactone and lactide derivatives will be published simultaneously with this document. Please refer to Belsito et al., 2011 for an overall assessment of the safe use of this material and all macrocyclic lactone and lactide derivatives in fragrances. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of macrocylic lactones and lactide derivatives when used as fragrance ingredients. Copyright © 2011. Published by Elsevier Ltd.

Fire Safety Aspects of Polymeric Materials. Volume 3. Smoke and Toxicity (Combustion Toxicology of Polymers)

DTIC Science & Technology

1978-01-01

Analytical Test Methodology Sampling and analysis of thermal decomposition products are formidable tasks (Rasbash, 1967; Gaskill, 1973; Bankston ...by a flowing solution. A Sample Gas Inlet B Alkali Solution Inlet C Gas and Solution Outlet D Specific Ion Electrode E Reference Electrode E D 1 0 1 2...of radiant heat (Zinn, Powell, Cassanova and Bankston , 1977) ° Seader and Ou have recently proposed a theory relating optical density to particulate

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 97

NASA Technical Reports Server (NTRS)

1972-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 94)

NASA Technical Reports Server (NTRS)

1971-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 96

NASA Technical Reports Server (NTRS)

1971-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

Aerospace medicine and biology: A continuing bibliography with indexes, supplement

NASA Technical Reports Server (NTRS)

1972-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 100)

NASA Technical Reports Server (NTRS)

1972-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. Reference describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

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

EPA Science Inventory

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

[Regulations for decontamination of surfaces polluted as a result of chemical accidents (concept approaches)].

PubMed

Filatov, B N; Britanov, N G; Tochilkina, L P; Zhukov, V E; Maslennikov, A A; Ignatenko, M N; Volchek, K

2011-01-01

The threat of industrial chemical accidents and terrorist attacks requires the development of safety regulations for the cleanup of contaminated surfaces. This paper presents principles and a methodology for the development of a new toxicological parameter, "relative value unit" (RVU) as the primary decontamination standard.

The Evolution of Toxicology and Chemical Regulation ...

EPA Pesticide Factsheets

Presentation for lecture for the 17th Annual Sitlington Lecture in Toxicology at Oklahoma State University Interdisciplinary Toxicology Symposium Presentation for lecture for the 17th Annual Sitlington Lecture in Toxicology at Oklahoma State University Interdisciplinary Toxicology Symposium

[The Journal de chimie médicale (Journal of Medical Chemistry) : a major innovation on French public health during the 19th century ].

PubMed

Bonnemain, Bruno

2017-03-01

JBA Chevallier is first known for his publication in 1850 of his book on falsifications. But he had also a major role for the opening of the pharmacy world to toxicological and Public Health issues, through the founding in 1825, and the management for more than 50 years, of the Journal de chimie médicale, de pharmacie et de toxicologie (Journal of Medical Chemistry, of Pharmacy and of Toxicology). The purpose of the present study has been to look at the evolution of that publication over the years and to compare its content with the reference pharmaceutical journal at that time : the Journal de pharmacie et de chimie (Journal of Pharmacy and Chemistry). One can observe that the editorial lines of both journals will progressively diverge from each other, but Chevallier remained strongly connected with pharmacy, his journal merging finally in 1876 with the Répertoire de pharmacie (Index of Pharmacy).

Risk assessment for pesticides' MRL non-compliances in Poland in the years 2011-2015.

PubMed

Struciński, Paweł; Ludwicki, Jan K; Góralczyk, Katarzyna; Czaja, Katarzyna; Hernik, Agnieszka; Liszewska, Monika

2015-01-01

Human exposure to trace levels of pesticide residues present in food of plant origin is inevitable as long as pesticides continue to be applied in agriculture. Since Maximum Residue Levels (MRL) are not toxicological endpoint values, their violation is not by default equivalent to health risk for consumers. However, its essential to provide a health- based risk assessment for each case of MRL non-compliance reported during monitoring and official control of foodstuffs. To assess the potential short-term risk associated with consumption of food products of plant origin containing pesticide residues above MRL values based on notifications forwarded by the National Contact Point for RASFF in Poland during 2011-2015. 115 notifications including 127 analytical results non-compliant with respective MRL values were forwarded to provide risk assessment. An internationally accepted deterministic approach based on conservative model assumptions for short-term exposure assessment was applied. The risk was characterized by comparing an estimated dietary intake with respective acute reference dose (ARfD). Black currant, tea, lettuce, Chinese cabbage and carrot were among the most frequently notified products in years 2011-2015. Among pesticides exceeding respective MRL values, over 90% belonged to fungicides and insecticides/acaricides such as acetamiprid, chlorpyrifos, dimethoate, imidacloprid, dithiocarbamates and procymidone. For 15 and 6 results noncompliant with respective MRL value, a predicted short-term intake exceeded ARfD for children and adults, respectively. Residue levels that could potentially pose a health threat are found incidentally. The science-based and transparent risk assessment process with regard to the data, methods and assumptions that are applied is essential to risk management authorities. risk assessment, pesticide residues, MRL, dietary intake, RASFF, food safety.

TOXICOLOGICAL EVALUATION OF REALISTIC EMISSIONS OF SOURCE AEROSOLS (TERESA): APPLICATION TO POWER PLANT-DERIVED PM2.5

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

Annette Rohr

2004-12-02

This report documents progress made on the subject project during the period of March 1, 2004 through August 31, 2004. The TERESA Study is designed to investigate the role played by specific emissions sources and components in the induction of adverse health effects by examining the relative toxicity of coal combustion and mobile source (gasoline and/or diesel engine) emissions and their oxidative products. The study involves on-site sampling, dilution, and aging of coal combustion emissions at three coal-fired power plants, as well as mobile source emissions, followed by animal exposures incorporating a number of toxicological endpoints. The DOE-EPRI Cooperative Agreementmore » (henceforth referred to as ''the Agreement'') for which this technical progress report has been prepared covers the analysis and interpretation of the field data collected at the first power plant (henceforth referred to as Plant 0, and located in the Upper Midwest), followed by the performance and analysis of similar field experiments at two additional coal-fired power plants (Plants 1 and 2) utilizing different coal types and with different plant configurations. Significant progress was made on the Project during this reporting period, with field work being initiated at Plant 0. Initial testing of the stack sampling system and reaction apparatus revealed that primary particle concentrations were lower than expected in the emissions entering the mobile chemical laboratory. Initial animal exposures to primary emissions were carried out (Scenario 1) to ensure successful implementation of all study methodologies and toxicological assessments. Results indicated no significant toxicological effects in response to primary emissions exposures. Exposures were then carried out to diluted, oxidized, neutralized emissions with the addition of secondary organic aerosol (Scenario 5), both during the day and also at night when primary particle concentrations in the sampled stack emissions tended to be slightly higher. Exposure concentrations were about 249 {micro}g/m{sup 3} PM, of which 87 {micro}g/m{sup 3} was sulfate and approximately 110 {micro}g/m{sup 3} was secondary organic material ({approx}44%). Results indicated subtle differences in breathing pattern between exposed and control (sham) animals, but no differences in other endpoints (in vivo chemiluminescence, blood cytology, bronchoalveolar lavage fluid analysis). It was suspected that primary particle losses may have been occurring in the venturi aspirator/orifice sampler; therefore, the stack sampling system was redesigned. The modified system resulted in no substantial increase in particle concentration in the emissions, leading us to conclude that the electrostatic precipitator at the power plant has high efficiency, and that the sampled emissions are representative of those exiting the stack into the atmosphere. This is important, since the objective of the Project is to carry out exposures to realistic coal combustion-derived secondary PM arising from power plants. During the next reporting period, we will document and describe the remainder of the fieldwork at Plant 0, which we expect to be complete by mid-November 2004. This report will include detailed Phase I toxicological findings for all scenarios run, and Phase II toxicological findings for one selected scenario. Depending upon the outcome of the ongoing fieldwork at Plant 0 (i.e. the biological effects observed), not all the proposed scenarios may be evaluated. The next report is also expected to include preliminary field data for Plant 1, located in the Southeast.« less

Computational toxicity in 21st century safety sciences (China ...

EPA Pesticide Factsheets

presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China

The Toxicology Education Summit: Building the Future of Toxicology Through Education

PubMed Central

Barchowsky, Aaron; Buckley, Lorrene A.; Carlson, Gary P.; Fitsanakis, Vanessa A.; Ford, Sue M.; Genter, Mary Beth; Germolec, Dori R.; Leavens, Teresa L.; Lehman-McKeeman, Lois D.; Safe, Stephen H.; Sulentic, Courtney E. W.; Eidemiller, Betty J.

2012-01-01

Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collaborative approaches that require advanced and continuing education in toxicology and associated disciplines. This requires paradigm shifts in educational programs that support recruitment, development, and training of the modern toxicologist, as well as continued education and retraining of the midcareer professional to keep pace and sustain careers in industry, government, and academia. The Society of Toxicology convened the Toxicology Educational Summit to discuss the state of toxicology education and to strategically address educational needs and the sustained advancement of toxicology as a profession. The Summit focused on core issues of: building for the future of toxicology through educational programs; defining education and training needs; developing the “Total Toxicologist”; continued training and retraining toxicologists to sustain their careers; and, finally, supporting toxicology education and professional development. This report summarizes the outcomes of the Summit, presents examples of successful programs that advance toxicology education, and concludes with strategies that will insure the future of toxicology through advanced educational initiatives. PMID:22461448

The Toxicology Education Summit: building the future of toxicology through education.

PubMed

Barchowsky, Aaron; Buckley, Lorrene A; Carlson, Gary P; Fitsanakis, Vanessa A; Ford, Sue M; Genter, Mary Beth; Germolec, Dori R; Leavens, Teresa L; Lehman-McKeeman, Lois D; Safe, Stephen H; Sulentic, Courtney E W; Eidemiller, Betty J

2012-06-01

Toxicology and careers in toxicology, as well as many other scientific disciplines, are undergoing rapid and dramatic changes as new discoveries, technologies, and hazards advance at a blinding rate. There are new and ever increasing demands on toxicologists to keep pace with expanding global economies, highly fluid policy debates, and increasingly complex global threats to public health. These demands must be met with new paradigms for multidisciplinary, technologically complex, and collaborative approaches that require advanced and continuing education in toxicology and associated disciplines. This requires paradigm shifts in educational programs that support recruitment, development, and training of the modern toxicologist, as well as continued education and retraining of the midcareer professional to keep pace and sustain careers in industry, government, and academia. The Society of Toxicology convened the Toxicology Educational Summit to discuss the state of toxicology education and to strategically address educational needs and the sustained advancement of toxicology as a profession. The Summit focused on core issues of: building for the future of toxicology through educational programs; defining education and training needs; developing the "Total Toxicologist"; continued training and retraining toxicologists to sustain their careers; and, finally, supporting toxicology education and professional development. This report summarizes the outcomes of the Summit, presents examples of successful programs that advance toxicology education, and concludes with strategies that will insure the future of toxicology through advanced educational initiatives.

[Concerning the crisis of the West German politics of limit values in the 1970s: the transformation of cancer at the workplace from a toxicological into a socioeconomic problem].

PubMed

Bächi, Beat

2010-12-01

The paper tackles the changes that occurred in the political culture and the episteme of risk in the Federal Republic of Germany in the 1970s. The objects of observation are limit values for hazardous industrial materials, especially for carcinogens. At the forefront of the production of such values in Germany was the German Research Society's Senate Commission for the Examination of Hazardous Industrial Materials. Limit values bring economy, politics, and science together and they mediate different interests. This makes limit values an ideal object of study to bring together changes in different parts of society. In 1972, a new category of limit values for carcinogenic substances is introduced, the so called "Technische Richtkonzentration" (TRK). This category of values does not assume that complete safety can be reached, as do limit values for hazardous industrial materials, so called "Maximale Arbeitsplatzkonzentrationen" (MAK). This means an important rupture in toxicological thinking. Until the 1970s, Paracelsus' dictum about dosage and poison still served as starting point for toxicologists. The innovation of TRK marks an important rupture in the episteme of regulating dangerous matters. Whereas until the 1970s there existed, at least as an ideal, the myth of "no risk" or "zero tolerance" even in the case of carcinogens, since the beginning of the 1970s, certainty is no more guaranteed by epistemically, but by socially robust knowledge. This also means the return of the risk society at the beginning of the 1970s, whereby cancer at the workplace becomes--in the view of the regulatory bodies--out of a medical problem a socioeconomic illness. The paper argues that these changes are connected to a general feeling of disorientation.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

78 FR 45253 - National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-26

... Scientific Advisory Committee on Alternative Toxicological Methods; Announcement of Meeting; Request for... Toxicological Methods (SACATM). SACATM advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of...

The Role of Toxicology in the Pharmacy Curriculum

ERIC Educational Resources Information Center

Autian, John; Wood, George

1976-01-01

The past history of toxicology courses, recent trends, departments or divisions of toxicology, undergraduate and graduate courses, and residency programs are described. The emphasis of clinical toxicology in the University of Tennessee program is discussed, along with the school's Drug and Toxicology Information Center. (LBH)

A multi-disciplinary approach to the removal of emerging contaminants in municipal wastewater treatment plants in New York state (2003-2004)

USGS Publications Warehouse

Philips, Patrick J.; Stinson, Beverley; Zaugg, Steven D.; Furlong, Edward T.; Kolpin, Dana W.; Esposito, Kathleen; Bodniewicz, B.; Pape, R.; Anderson, J.

2008-01-01

Across the United States, there is a rapidly growing awareness of the occurrence and the toxicological impacts of natural and synthetic trace compounds in the environment. These trace compounds, referred to as emerging contaminants (ECs), are reported to cause a range of negative impacts in the environment, such as adverse effects on biota in receiving streams and interference with the normal functions of the endocrine system, which controls growth and development in living organisms.

A cumulative index to a continuing bibliography on aerospace medicine and biology, January 1972

NASA Technical Reports Server (NTRS)

1972-01-01

Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

The various aspects of genetic and epigenetic toxicology: testing methods and clinical applications.

PubMed

Ren, Ning; Atyah, Manar; Chen, Wan-Yong; Zhou, Chen-Hao

2017-05-22

Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.

Aerospace Medicine and Biology: A Continuing Bibliography With Indexes

NASA Technical Reports Server (NTRS)

1997-01-01

This issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes NASA SP-7O11 lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 475

NASA Technical Reports Server (NTRS)

1998-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Predictive Toxicology: Current Status and Future Outlook (EBI ...

EPA Pesticide Factsheets

Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA. Slide presentation at the EBI-EMBL Industry Programme Workshop on Predictive Toxicology and the currently status of Computational Toxicology activities at the US EPA.

Cornerstones of Toxicology.

PubMed

Hayes, A Wallace; Dixon, Darlene

2017-01-01

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).

Cornerstones of Toxicology

PubMed Central

Hayes, A. Wallace; Dixon, Darlene

2016-01-01

The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, CA, focused on “The Basis and Relevance of Variation in Toxicologic Responses. In order to review the basic tenants of toxicology a ‘broad brush” interactive talk was presented that gave an overview of the Cornerstones of Toxicology. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation). PMID:28068892

Toxicology: a discipline in need of academic anchoring--the point of view of the German Society of Toxicology.

PubMed

Gundert-Remy, U; Barth, H; Bürkle, A; Degen, G H; Landsiedel, R

2015-10-01

The paper describes the importance of toxicology as a discipline, its past achievements, current scientific challenges, and future development. Toxicological expertise is instrumental in the reduction of human health risks arising from chemicals and drugs. Toxicological assessment is needed to evaluate evidence and arguments, whether or not there is a scientific base for concern. The immense success already achieved by toxicological work is exemplified by reduced pollution of air, soil, water, and safer working places. Predominantly predictive toxicological testing is derived from the findings to assess risks to humans and the environment. Assessment of the adversity of molecular effects (including epigenetic effects), the effects of mixtures, and integration of exposure and biokinetics into in vitro testing are emerging challenges for toxicology. Toxicology is a translational science with its base in fundamental science. Academic institutions play an essential part by providing scientific innovation and education of young scientists.

Massive intoxication involving unusual high concentration of amitriptyline.

PubMed

Margalho, Cláudia; Barroso, Mário; Gallardo, Eugenia; Monsanto, Paula; Vieira, Duarte Nuno

2007-08-01

Amitriptyline is a tricyclic antidepressant widely used in the treatment of depression. Antidepressant drugs are among the most commonly encountered causes of self-poisoning, as illustrated by several published cases in the literature. This investigation reports a case of massive amitriptyline intoxication, involving a 44-year old female found dead in bed. The presence of this tricyclic antidepressant was revealed by a routine screening procedure. The concentration was calculated by gas chromatography/ electron ionization-mass spectrometry in the selected ion monitoring mode after solid-phase extraction using proadifen as internal standard and was in the post-mortem whole blood sample 85.9 mug/mL. This value was much higher than the reported toxic values ever found in the literature, and may therefore have caused the victim's death. Nortriptyline was also detected in the toxic concentration range, as well as therapeutic levels of diazepam and nor-diazepam. Taking into account both the available circumstantial information and toxicological results, it is very likely that death was caused by self-poisoning. Human & Experimental Toxicology (2007) 26, 667-670.

Compilation of Physicochemical and Toxicological Information ...

EPA Pesticide Factsheets

The purpose of this product is to make accessible the information about the 1,173 hydraulic fracturing-related chemicals that were listed in the external review draft of the Hydraulic Fracturing Drinking Water Assessment that was released recently. The product consists of a series of spreadsheets with physicochemical and toxicological information pulled from several sources of information, including: EPI Suite, LeadScope, QikiProp, Reaxys, IRIS, PPRTV, ATSDR, among other sources. The spreadsheets also contain background information about how the list of chemicals were compiled, what the different sources of chemical information are, and definitions and descriptions of the values presented. The purpose of this product is to compile and make accessible information about the 1,173 hydraulic fracturing-related chemicals listed in the external review draft of the Hydraulic Fracturing Drinking Water Assessment.

COMPUTATIONAL TOXICOLOGY-WHERE IS THE DATA? ...

EPA Pesticide Factsheets

This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource). This talk will briefly describe the state of the data world for computational toxicology and one approach to improve the situation, called ACToR (Aggregated Computational Toxicology Resource).

Forensic Toxicology: An Introduction.

PubMed

Smith, Michael P; Bluth, Martin H

2016-12-01

This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline. Copyright © 2016 Elsevier Inc. All rights reserved.

The toxicological significance of post-mortem drug concentrations in bile.

PubMed

Ferner, Robin E; Aronson, Jeffrey K

2018-01-01

Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile concentrations exceeded blood concentrations by one order of magnitude for several drugs, including dihydrocodeine, quetiapine and sildenafil; and by two orders of magnitude of for buprenorphine, colchicine and 3,4-methylenedioxy-methamphetamine (MDMA), among others. The minimum and maximum values for the ratio differed by a factor of three or more in three-quarters of the cases where data were available and by a factor of 10 or more for over half of the analytes. The data were difficult to find. Medline does not explicitly index the term "drug bile concentration". It may well be that other reports exist, although they would not alter our major conclusion. Many of the papers that contributed data failed to specify the source of the blood samples or the post-mortem interval, so that no judgment was possible regarding post-mortem redistribution in whole blood or bile. For most drugs, there are wide ranges of bile:blood concentration ratios, which means that bile and blood concentrations are generally poorly correlated. Bile concentration measurements cannot readily be used to establish post-mortem blood concentrations; nor can they be extrapolated to ante-mortem concentrations. However, because drug concentrations in bile often exceed those in blood, bile may allow qualitative identification of drugs present, even when the blood concentration is below the limit of detection.

Jatropha gossypiifolia L. (Euphorbiaceae): A Review of Traditional Uses, Phytochemistry, Pharmacology, and Toxicology of This Medicinal Plant

PubMed Central

Félix-Silva, Juliana; Giordani, Raquel Brandt; da Silva-Jr, Arnóbio Antonio; Zucolotto, Silvana Maria; Fernandes-Pedrosa, Matheus de Freitas

2014-01-01

Jatropha gossypiifolia L. (Euphorbiaceae), widely known as “bellyache bush,” is a medicinal plant largely used throughout Africa and America. Several human and veterinary uses in traditional medicine are described for different parts and preparations based on this plant. However, critical reviews discussing emphatically its medicinal value are missing. This review aims to provide an up-to-date overview of the traditional uses, as well as the phytochemistry, pharmacology, and toxicity data of J. gossypiifolia species, in view of discussing its medicinal value and potential application in complementary and alternative medicine. Pharmacological studies have demonstrated significant action of different extracts and/or isolated compounds as antimicrobial, anti-inflammatory, antidiarrheal, antihypertensive, and anticancer agents, among others, supporting some of its popular uses. No clinical trial has been detected to date. Further studies are necessary to assay important folk uses, as well as to find new bioactive molecules with pharmacological relevance based on the popular claims. Toxicological studies associated with phytochemical analysis are important to understand the eventual toxic effects that could reduce its medicinal value. The present review provides insights for future research aiming for both ethnopharmacological validation of its popular use and its exploration as a new source of herbal drugs and/or bioactive natural products. PMID:25002902

Antioxidant capacity versus chemical safety of wheat bread enriched with pomegranate peel powder.

PubMed

Altunkaya, Arzu; Hedegaard, Rikke V; Brimer, Leon; Gökmen, Vural; Skibsted, Leif H

2013-04-30

Pomegranate peel powder (PP), a by-product of the pomegranate juice industry rich in polyphenols, was explored for use in bread production, due to its potential health effects. Wheat bread was prepared using different levels for replacement of flour with PP (0 to 10 g per 100 g flour) resulting in antioxidant levels expressed as Trolox equivalent antioxidant capacity values (TEAC) ranging from 1.8 to 6.8 μmol TEAC per g bread for fresh bread. TEAC remained constant during 5 days of storage in polyethylene bags at room temperature. The oxidative stability was evaluated by detection of radicals by direct electron spin resonance (ESR) spectroscopy, and peroxide value, and the highest capacity of scavenging of radicals (Fremy's salt) and the lowest content of peroxide values were found in bread with the highest percentage of PP. Safety evaluation was performed by the Artemia salina assay. An increased death rate of the brine shrimp larvae was found as a function of the replacement of wheat flour with PP in fortified bread providing a general screening method for the toxicological test of polyphenol fortified bread to be recommended for use in product development in addition to subjective evaluation. Based on both toxicological and subjective evaluations an addition of 2.5% PP is recommended for the actual product.

Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations.

PubMed

Dolan, David G; Naumann, Bruce D; Sargent, Edward V; Maier, Andrew; Dourson, Michael

2005-10-01

A scientific rationale is provided for estimating acceptable daily intake values (ADIs) for compounds with limited or no toxicity information to support pharmaceutical manufacturing operations. These ADIs are based on application of the "thresholds of toxicological concern" (TTC) principle, in which levels of human exposure are estimated that pose no appreciable risk to human health. The same concept has been used by the US Food and Drug Administration (FDA) to establish "thresholds of regulation" for indirect food additives and adopted by the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In practice, these values are used as a statement of safety and indicate when no actions need to be taken in a given exposure situation. Pharmaceutical manufacturing relies on ADIs for cleaning validation of process equipment and atypical extraneous matter investigations. To provide practical guidance for handling situations where relatively unstudied compounds with limited or no toxicity data are encountered, recommendations are provided on ADI values that correspond to three categories of compounds: (1) compounds that are likely to be carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3) compounds that are not likely to be potent, highly toxic or carcinogenic. Corresponding ADIs for these categories of materials are 1, 10, and 100 microg/day, respectively.

Conservative Exposure Predictions for Rapid Risk Assessment of Phase-Separated Additives in Medical Device Polymers.

PubMed

Chandrasekar, Vaishnavi; Janes, Dustin W; Saylor, David M; Hood, Alan; Bajaj, Akhil; Duncan, Timothy V; Zheng, Jiwen; Isayeva, Irada S; Forrey, Christopher; Casey, Brendan J

2018-01-01

A novel approach for rapid risk assessment of targeted leachables in medical device polymers is proposed and validated. Risk evaluation involves understanding the potential of these additives to migrate out of the polymer, and comparing their exposure to a toxicological threshold value. In this study, we propose that a simple diffusive transport model can be used to provide conservative exposure estimates for phase separated color additives in device polymers. This model has been illustrated using a representative phthalocyanine color additive (manganese phthalocyanine, MnPC) and polymer (PEBAX 2533) system. Sorption experiments of MnPC into PEBAX were conducted in order to experimentally determine the diffusion coefficient, D = (1.6 ± 0.5) × 10 -11  cm 2 /s, and matrix solubility limit, C s  = 0.089 wt.%, and model predicted exposure values were validated by extraction experiments. Exposure values for the color additive were compared to a toxicological threshold for a sample risk assessment. Results from this study indicate that a diffusion model-based approach to predict exposure has considerable potential for use as a rapid, screening-level tool to assess the risk of color additives and other small molecule additives in medical device polymers.

Understanding alterations on blood and biochemical parameters in athletes that use dietary supplements, steroids and illicit drugs.

PubMed

Bordin, Dayanne Mozaner; Bettim, Bárbara Beltrame; Perdona, Gleici Castro; de Campos, Eduardo Geraldo; De Martinis, Bruno Spinosa

2017-02-01

In recent years it was verified there are an alarming growing number of teenagers and young adults using a combination of dietary supplements (DS) anabolic androgenic steroids (AAS) and drugs of abuse. This practice is used to improve physical fitness and appearance, may cause serious side effects. This article shows the alterations in the hematological and renal function parameters associate with these substances in 40 athletes. This research involved three steps: 1-the administration of a self-completion questionnaire ; 2-the assessment of hematological and biochemical parameters of renal function and; 3-toxicological urinalysis. Hematological and biochemical tests were conducted in an accredited laboratory and the toxicological urinalysis was validated in our laboratory using liquid-liquid extraction (LLE) and gas chromatography-mass spectrometry (GC-MS). The testosterone levels in the participants who consumed steroids increased 20-60% and alterations in serum creatinine, urea and uric reached values of up to 1.9; 60.6 and 7.5mg/dL, respectively. The toxicological urinalysis supports self-reports confirming the use of AAS and recreational drugs, putting at risk the health of those athletes increasing the chances of kidney diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the First Year of a Novel Toxicology Education Project.

PubMed

Wong, Anselm; Vohra, Rais; Ruha, Anne-Michelle; Koutsogiannis, Zeff; Graeme, Kimberlie; Dargan, Paul I; Wood, David M; Greene, Shaun L

2015-09-01

The international boundaries to medical education are becoming less marked as new technologies such as multiuser videoconferencing are developed and become more accessible to help bridge the communication gaps. The Global Educational Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries with established clinical toxicology services to clinicians in countries without clinical toxicologists around the globe. Centers that manage or consult on toxicology cases were registered through the American College of Medical Toxicology website via Survey Monkey®. Data was analyzed retrospectively from February 2014 to January 2015. Google hangouts® was used as the main conferencing software, but some sites preferred the use of Skype®. Registration data included contact details and toxicology background and qualifications. Thirty sites in 19 different countries in Australasia, Europe, Africa, and America were registered. Twenty-eight (93 %) sites were located in a major urban center, one (3.5 %) site in a major rural center and one (3.5 %) a private practice. Expectations of GETUP included sharing toxicology cases and education (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %), assistance with providing a toxicology teaching curriculum in languages other than English (2, 7 %), and managing toxicology presentations in resource-poor settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty-two conferences were performed during the first 12 months with a mean of 3 cases per conference. GETUP has connected countries and clinical units with and without toxicology services and will provide a platform to improve international collaboration in clinical toxicology.

From the Cover: Manganese Stimulates Mitochondrial H2O2 Production in SH-SY5Y Human Neuroblastoma Cells Over Physiologic as well as Toxicologic Range

PubMed Central

Fernandes, Jolyn; Hao, Li; Bijli, Kaiser M.; Chandler, Joshua D.; Orr, Michael; Hu, Xin; Jones, Dean P.

2017-01-01

Manganese (Mn) is an abundant redox-active metal with well-characterized mitochondrial accumulation and neurotoxicity due to excessive exposures. Mn is also an essential co-factor for the mitochondrial antioxidant protein, superoxide dismutase-2 (SOD2), and the range for adequate intake established by the Institute of Medicine Food and Nutrition Board is 20% of the interim guidance value for toxicity by the Agency for Toxic Substances and Disease Registry, leaving little margin for safety. To study toxic mechanisms over this critical dose range, we treated human neuroblastoma SH-SY5Y cells with a series of MnCl2 concentrations (from 0 to 100 μM) and measured cellular content to compare to human brain Mn content. Concentrations ≤10 μM gave cellular concentrations comparable to literature values for normal human brain, whereas concentrations ≥50 μM resulted in values comparable to brains from individuals with toxic Mn exposures. Cellular oxygen consumption rate increased as a function of Mn up to 10 μM and decreased with Mn dose ≥50 μM. Over this range, Mn had no effect on superoxide production as measured by aconitase activity or MitoSOX but increased H2O2 production as measured by MitoPY1. Consistent with increased production of H2O2, SOD2 activity, and steady-state oxidation of total thiol increased with increasing Mn. These findings have important implications for Mn toxicity by re-directing attention from superoxide anion radical to H2O2-dependent mechanisms and to investigation over the entire physiologic range to toxicologic range. Additionally, the results show that controlled Mn exposure provides a useful cell manipulation for toxicological studies of mitochondrial H2O2 signaling. PMID:27701121

Human adipose-derived stem cells (ADSC) and human periodontal ligament stem cells (PDLSC) as cellular substrates of a toxicity prediction assay.

PubMed

Corrêa, Natássia Caroline Resende; Kuligovski, Crisciele; Paschoal, Ariane Caroline Campos; Abud, Ana Paula Ressetti; Rebelatto, Carmen Lucia Kuniyoshi; Leite, Lidiane Maria Boldrini; Senegaglia, Alexandra Cristina; Dallagiovanna, Bruno; Aguiar, Alessandra Melo de

2018-02-01

With the increasing need to develop in vitro assays to replace animal use, human stem cell-derived methods are emerging and showing outstanding contributions to the toxicological screening of substances. Adult human stem cells such as adipose-derived stem cells (ADSC) and periodontal ligament stem cells (PDLSC) were used as cell substrates for a cytotoxicity assay and toxicity prediction using the neutral red uptake (NRU) assay. First, primary cell cultures from three independent donors, from each tissue source, were characterized as mesenchymal stem cells (MSC) by plastic adherence and appropriate immunophenotype for MSC markers (positive for CD90, CD73, and CD105 and negative for CD11b, CD34, CD45, HLADR, and CD19). Furthermore, ADSC and PDLSC were able to differentiate into adipocytes and osteoblasts when maintained under the same culture conditions previously established for the NRU assay. NRU assays for three reference test substances were performed. R 2 was higher than 0.85 for all conditions, showing the feasibility to calculate IC 50 values. The IC 50 values were then used to predict the LD 50 of the test substances, which were comparable to previous results and the ICCVAM standard test report. Primary ADSC and PDLSC showed the potential to be considered as additional models for use in cytotoxicity assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary intake of dioxins, furans and dioxin-like PCBs in Austria.

PubMed

Rauscher-Gabernig, Elke; Mischek, Daniela; Moche, Wolfgang; Prean, Michael

2013-01-01

Human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like PCBs (dl-PCBs) should be assessed regularly. In order to evaluate the contamination levels in various food products on the Austrian market and to assess the dietary exposure of the Austrian population for the first time, a national monitoring programme was conducted from 2005 to 2011. The 235 food products comprised meat, poultry, game and offal, fish and fish products, milk and dairy products, eggs, animal fats and vegetable oils. To estimate the dietary intakes of PCDD/Fs and dl-PCBs, mean concentrations in food were combined with the respective food consumption data from the Austrian food consumption survey. Estimated dietary intakes were expressed as toxic equivalents (WHO-TEQs 1998). The mean intakes for PCDD/Fs and dl-PCBs were estimated as 0.77, 0.75 and 0.61 pg WHO-TEQ kg(-1) bw day(-1) for children, women and men, respectively. The main contributors to total intake were milk and dairy products followed by fish and fish products for children and women, and meat, poultry, game and offal for men (65% and 15% for children, 67% and 14% for women, and 63% and 19% for men, respectively). Comparison of the estimated dietary intakes with the toxicological reference values shows that both children and adults are well below those values.

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

DTIC Science & Technology

1984-04-01

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

ACToR-AGGREGATED COMPUTATIONAL TOXICOLOGY ...

EPA Pesticide Factsheets

One goal of the field of computational toxicology is to predict chemical toxicity by combining computer models with biological and toxicological data. predict chemical toxicity by combining computer models with biological and toxicological data

National Toxicology Program

MedlinePlus

... develops and applies tools of modern toxicology and molecular biology to identify substances in the environment that may ... application of new technologies for modern toxicology and molecular biology. A world leader in toxicology research, NTP has ...

Using High-Content Imaging to Analyze Toxicological Tipping Points (ICTATT meeting China)

EPA Science Inventory

Presentation at International Conference on Toxicological Alternatives & Translational Toxicology (ICTATT) held in China and Discussing the possibility of using High Content Imaging to Analyze Toxicological Tipping Points

The Emergence of Systematic Review in Toxicology.

PubMed

Stephens, Martin L; Betts, Kellyn; Beck, Nancy B; Cogliano, Vincent; Dickersin, Kay; Fitzpatrick, Suzanne; Freeman, James; Gray, George; Hartung, Thomas; McPartland, Jennifer; Rooney, Andrew A; Scherer, Roberta W; Verloo, Didier; Hoffmann, Sebastian

2016-07-01

The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

The influence of global climate change on the scientific foundations and applications of Environmental Toxicology and Chemistry: introduction to a SETAC international workshop.

PubMed

Stahl, Ralph G; Hooper, Michael J; Balbus, John M; Clements, William; Fritz, Alyce; Gouin, Todd; Helm, Roger; Hickey, Christopher; Landis, Wayne; Moe, S Jannicke

2013-01-01

This is the first of seven papers resulting from a Society of Environmental Toxicology and Chemistry (SETAC) international workshop titled "The Influence of Global Climate Change on the Scientific Foundations and Applications of Environmental Toxicology and Chemistry." The workshop involved 36 scientists from 11 countries and was designed to answer the following question: How will global climate change influence the environmental impacts of chemicals and other stressors and the way we assess and manage them in the environment? While more detail is found in the complete series of articles, some key consensus points are as follows: (1) human actions (including mitigation of and adaptation to impacts of global climate change [GCC]) may have as much influence on the fate and distribution of chemical contaminants as does GCC, and modeled predictions should be interpreted cautiously; (2) climate change can affect the toxicity of chemicals, but chemicals can also affect how organisms acclimate to climate change; (3) effects of GCC may be slow, variable, and difficult to detect, though some populations and communities of high vulnerability may exhibit responses sooner and more dramatically than others; (4) future approaches to human and ecological risk assessments will need to incorporate multiple stressors and cumulative risks considering the wide spectrum of potential impacts stemming from GCC; and (5) baseline/reference conditions for estimating resource injury and restoration/rehabilitation will continually shift due to GCC and represent significant challenges to practitioners. Copyright © 2013 SETAC.

The influence of global climate change on the scientific foundations and applications of Environmental Toxicology and Chemistry: Introduction to a SETAC international workshop

USGS Publications Warehouse

Stahl, Ralph G.; Hooper, Michael J.; Balbus, John M.; Clements, William; Fritz, Alyce; Gouin, Todd; Helm, Roger; Hickey, Christopher; Landis, Wayne; Moe, S. Jannicke

2013-01-01

This is the first of seven papers resulting from a Society of Environmental Toxicology and Chemistry (SETAC) international workshop titled “The Influence of Global Climate Change on the Scientific Foundations and Applications of Environmental Toxicology and Chemistry.” The workshop involved 36 scientists from 11 countries and was designed to answer the following question: How will global climate change influence the environmental impacts of chemicals and other stressors and the way we assess and manage them in the environment? While more detail is found in the complete series of articles, some key consensus points are as follows: (1) human actions (including mitigation of and adaptation to impacts of global climate change [GCC]) may have as much influence on the fate and distribution of chemical contaminants as does GCC, and modeled predictions should be interpreted cautiously; (2) climate change can affect the toxicity of chemicals, but chemicals can also affect how organisms acclimate to climate change; (3) effects of GCC may be slow, variable, and difficult to detect, though some populations and communities of high vulnerability may exhibit responses sooner and more dramatically than others; (4) future approaches to human and ecological risk assessments will need to incorporate multiple stressors and cumulative risks considering the wide spectrum of potential impacts stemming from GCC; and (5) baseline/reference conditions for estimating resource injury and restoration/rehabilitation will continually shift due to GCC and represent significant challenges to practitioners.

Acute pesticide poisoning related deaths in Tehran during the period 2003-2004.

PubMed

Soltaninejad, Kambiz; Faryadi, Mansoor; Sardari, Fariba

2007-08-01

Acute pesticide poisoning is an important cause of morbidity and mortality in Iran and worldwide. Determination of inducing factors in pesticide poisoning is very important parameter for planning of preventive and controlling programs. The aim of present study is assessing of effects of epidemiological variables on fatal pesticide poisoning. Data was obtained from autopsies on suspected pesticide poisoning deaths were performed in the Tehran Legal Medicine Center between 2003 and 2004. Among these medicolegal autopsies, fatal poisoning cases were evaluated retrospectively by reports of toxicological analysis. The variables such as age, sex, job, residential location, educational level, type of pesticide and cause of poisoning were reviewed. From total of 3885 autopsies referred to forensic toxicology laboratory for pesticide toxicology analysis, 51 (1.31%) deaths were due to pesticide poisoning. The age of cases was 32+/-17 years old. 63.3% of cases were male and 36.7% of them were female. The majority of cases (31.4%) were housekeeper and 23.5% were student. 66.7% of cases were lived in urban and 33.3% were lived in rural area. The most common type of poisoning was suicide (52.9%). 33.3% of cases had primary education. The common type of pesticide in this study was aluminum phosphide 18 (35.8%) and organophosphates 17 (33.3%). According to fatal aluminum phosphide poisoning, more stringent legislation and enforcement regarding the sale and distribution of this toxic substance is needed. Thus substitution of this pesticide with safer agents is necessary.

The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP): pharmacokinetic and pharmacodynamic clinical and forensic aspects.

PubMed

Nóbrega, Leandro; Dinis-Oliveira, Ricardo Jorge

2018-05-01

New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U.S. National Library of Medicine) and governmental websites without limitation of the period. α-PVP is a wide spread and easy to get special type of synthetic cathinone with seemingly powerful cocaine-like stimulant effects, high brain penetration, high liability for abuse and with increased risk of adverse effects such as tachycardia, agitation, hypertension, hallucinations, delirium, mydriasis, self-injury, aggressive behavior, and suicidal ideations. α-PVP undergoes extensive metabolism via different pathways and the α-PVP itself or its metabolites β-hydroxy-α-PVP and α-PVP lactam represent the main targets for toxicological analysis in urine. There is a limited knowledge regarding the short- and long-term effects of α-PVP and metabolites, and pharmacogenetic influence, hence further clinical and forensic toxicological studies are required. Moreover, since α-PVP cannot be detected with classic routine analysis procedures, statements on the frequency of their consumption cannot be made.

Diesel fumes do kill: a case of fatal carbon monoxide poisoning directly attributed to diesel fuel exhaust with a 10-year retrospective case and literature review*.

PubMed

Griffin, Sean M; Ward, Michael K; Terrell, Andrea R; Stewart, Donna

2008-09-01

While it is known that diesel fuel combustion engines produce much lower concentrations of carbon monoxide (CO) than gasoline engines, these emissions could certainly generate lethal ambient concentrations given a sufficient amount of time in an enclosed space and under suitable environmental conditions. The authors report a case of CO poisoning which was initially referred for autopsy as a presumed natural death of a truck driver found in the secure cab of a running diesel tractor trailer truck. Completion of the preliminary investigation ascribed death to complications of ischemic heart disease (IHD), pending toxicological analysis that included quantification of CO. When the toxicology results showed lethal blood COHbg, the cause of death was re-certified as CO intoxication secondary to inhalation of (diesel) vehicular exhaust fumes. Because of the unique source of fatal CO intoxication in this case, the contributory IHD and the possible contaminants in the putrefied blood, a 10-year retrospective review was conducted on all nonfire related CO deaths autopsied (n = 94) at the Office of the Chief Medical Examiner in Louisville, KY from 1994 to 2003. For validation of the COHbg detection method used by the Kentucky Office of Forensic Toxicology (KYOFT), blood samples from these cases along with controls were submitted to three laboratories using various analytical methods yielding no statistically significant differences. Lastly, an extensive literature review produced no scientifically reported cases of fatal CO poisoning attributed to diesel fuel exhaust.

Aluminum Phosphide Poisoning-Related Deaths in Tehran, Iran, 2006 to 2013

PubMed Central

Etemadi-Aleagha, Afshar; Akhgari, Maryam; Iravani, Fariba Sardari

2015-01-01

Abstract Metal phosphides such as aluminum phosphide are potent insecticides. This highly toxic substance is used for rice and other grains protection in Iran. Due to its high toxicity potential and easy availability, it is widely used as a suicide poison. This substance has no effective antidote and the incidence of deaths due to its poisoning is increasing day by day in Iran. The present study was conducted to show the increasing incidence of fatal aluminum phosphide poisoning and its toxicological and forensic aspects in an 8-year study, 2006 to 2013. Autopsy sheets were reviewed and cases with the history of aluminum phosphide poisoning were selected. Toxicological analysis results, demographic and necroscopic examination findings were studied. A total of 51.8% of studied cases were female. Most of the cases were between 10 and 40 years old. The manner of death was self-poisoning in 85% of cases. Morphine, ethanol, and amitriptyline were the most common additional drugs detected in toxicological analysis. The incidence of fatal aluminum phosphide poisoning cases referred for phosphine analysis was 5.22 and 37.02 per million of population of Tehran in 2006 and 2013, respectively. The results of this study showed that in spite of ban and restrictions, there was a dramatic increase in the incidence of fatal aluminum phosphide poisoning in Tehran from 2006 to 2013. Safety alert should be highlighted in training program for all population groups about the toxic effects of aluminum phosphide tablets. PMID:26402837

Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control.

PubMed

Ojanperä, Ilkka; Kolmonen, Marjo; Pelander, Anna

2012-05-01

Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography-mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology.

Towards a Fuzzy Expert System on Toxicological Data Quality Assessment.

PubMed

Yang, Longzhi; Neagu, Daniel; Cronin, Mark T D; Hewitt, Mark; Enoch, Steven J; Madden, Judith C; Przybylak, Katarzyna

2013-01-01

Quality assessment (QA) requires high levels of domain-specific experience and knowledge. QA tasks for toxicological data are usually performed by human experts manually, although a number of quality evaluation schemes have been proposed in the literature. For instance, the most widely utilised Klimisch scheme1 defines four data quality categories in order to tag data instances with respect to their qualities; ToxRTool2 is an extension of the Klimisch approach aiming to increase the transparency and harmonisation of the approach. Note that the processes of QA in many other areas have been automatised by employing expert systems. Briefly, an expert system is a computer program that uses a knowledge base built upon human expertise, and an inference engine that mimics the reasoning processes of human experts to infer new statements from incoming data. In particular, expert systems have been extended to deal with the uncertainty of information by representing uncertain information (such as linguistic terms) as fuzzy sets under the framework of fuzzy set theory and performing inferences upon fuzzy sets according to fuzzy arithmetic. This paper presents an experimental fuzzy expert system for toxicological data QA which is developed on the basis of the Klimisch approach and the ToxRTool in an effort to illustrate the power of expert systems to toxicologists, and to examine if fuzzy expert systems are a viable solution for QA of toxicological data. Such direction still faces great difficulties due to the well-known common challenge of toxicological data QA that "five toxicologists may have six opinions". In the meantime, this challenge may offer an opportunity for expert systems because the construction and refinement of the knowledge base could be a converging process of different opinions which is of significant importance for regulatory policy making under the regulation of REACH, though a consensus may never be reached. Also, in order to facilitate the implementation of Weight of Evidence approaches and in silico modelling proposed by REACH, there is a higher appeal of numerical quality values than nominal (categorical) ones, where the proposed fuzzy expert system could help. Most importantly, the deriving processes of quality values generated in this way are fully transparent, and thus comprehensible, for final users, which is another vital point for policy making specified in REACH. Case studies have been conducted and this report not only shows the promise of the approach, but also demonstrates the difficulties of the approach and thus indicates areas for future development. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Africa's present and future needs in toxicology education: Southern African perspective.

PubMed

Gulumian, Mary; Ginsburg, Carren; Stewart, Michael J

2005-09-01

Degrees and diplomas as well as certificates that are granted by universities and technikons in South Africa in scientific disciplines, such as forensic medicine, pharmacology, marine and veterinary sciences, environmental health, and occupational hygiene, include toxicology as one of the subjects in their overall syllabus. However, aspects of toxicology included in each of these courses are biased towards that particular subdiscipline and basic level of toxicology may be taught. Educational needs in toxicology in South Africa can be summarized as follows: (a) recognition of toxicology as a discipline in its own right at these tertiary education institutions and (b) creation of opportunities to study and obtain higher degrees in one or more of the many subdisciplines of toxicology. The results from a survey conducted on the toxicology syllabi offered at these tertiary education institutions are used to substantiate these needs.

Serbia National Poison Control Centre: organization and current activities.

PubMed

Jovanović, Dugan; Joksović, Dragan; Vucinić, Savica; Todorović, Veljko; Segrt, Zoran; Kilibarda, Vesna; Bokonjić, Dubravko

2005-01-01

Ministry of Health of the former Federal Republic of Yugoslavia established the National Poison Control Centre in 1995. However, that was only the formally solution since clinical, analytical and experimental services in toxicology had worked independently for at least 40 years. Besides the Headquarters, NPCC has currently 2 main units, the Clinic of Emergency and Clinical Toxicology and Pharmacology and the Institute of Toxicology and Pharmacology. The latter is consisted of Toxicological Information Department, Department of Analytical Toxicology and Department of Experimental Toxicology and Pharmacology. The Mobile Toxicological Chemical Unit is a separate department that is activated from personnel of the NPCC in a case of chemical accidents and/or disasters. Clinical, information and analytical parts of NPCC have a 365-day/24-hour working service. The Clinic of Emergency and Clinical Toxicology and Pharmacology is a place where the intoxicated patients are treated, including those that need the intensive care measures. Toxicological Information Department uses the data from a self-made computer Database for different information purposes. Department of Analytical Toxicology is equipped with a lot of contemporary analytical equipment that is giving the opportunity of identification and quantification of chemicals/metabolites/degradation products in biological material, food, water, air and soil. Basic pharmacological and toxicological research of chemicals and pre-clinical investigations of antidotes are realized in the Department of Experimental Toxicology and Pharmacology. In terms of medical prevention and rational treatment of human poison exposures in Serbia, the current organization of NPCC has so far proven to be effective.

A multiple testing approach for hazard evaluation of complex mixtures in the aquatic environment: the use of diesel oil as a model

USGS Publications Warehouse

Johnson, B. Thomas

1989-01-01

Traditional single species toxicity tests and multiple component laboratory-scaled microcosm assays were combined to assess the toxicological hazard of diesel oil, a model complex mixture, to a model aquatic environment. The immediate impact of diesel oil dosed on a freshwater community was studied in a model pond microcosm over 14 days: a 7-day dosage and a 7-day recovery period. A multicomponent laboratory microcosm was designed to monitor the biological effects of diesel oil (1·0 mg litre−1) on four components: water, sediment (soil + microbiota), plants (aquatic macrophytes and algae), and animals (zooplanktonic and zoobenthic invertebrates). To determine the sensitivity of each part of the community to diesel oil contamination and how this model community recovered when the oil dissipated, limnological, toxicological, and microbiological variables were considered. Our model revealed these significant occurrences during the spill period: first, a community production and respiration perturbation, characterized in the water column by a decrease in dissolved oxygen and redox potential and a concomitant increase in alkalinity and conductivity; second, marked changes in microbiota of sediments that included bacterial heterotrophic dominance and a high heterotrophic index (0·6), increased bacterial productivity, and the marked increases in numbers of saprophytic bacteria (10 x) and bacterial oil degraders (1000 x); and third, column water acutely toxic (100% mortality) to two model taxa: Selenastrum capricornutum and Daphnia magna. Following the simulated clean-up procedure to remove the oil slick, the recovery period of this freshwater microcosm was characterized by a return to control values. This experimental design emphasized monitoring toxicological responses in aquatic microcosm; hence, we proposed the term ‘toxicosm’ to describe this approach to aquatic toxicological hazard evaluation. The toxicosm as a valuable toxicological tool for screening aquatic contaminants was demonstrated using diesel oil as a model complex mixture.

MutAIT: an online genetic toxicology data portal and analysis tools.

PubMed

Avancini, Daniele; Menzies, Georgina E; Morgan, Claire; Wills, John; Johnson, George E; White, Paul A; Lewis, Paul D

2016-05-01

Assessment of genetic toxicity and/or carcinogenic activity is an essential element of chemical screening programs employed to protect human health. Dose-response and gene mutation data are frequently analysed by industry, academia and governmental agencies for regulatory evaluations and decision making. Over the years, a number of efforts at different institutions have led to the creation and curation of databases to house genetic toxicology data, largely, with the aim of providing public access to facilitate research and regulatory assessments. This article provides a brief introduction to a new genetic toxicology portal called Mutation Analysis Informatics Tools (MutAIT) (www.mutait.org) that provides easy access to two of the largest genetic toxicology databases, the Mammalian Gene Mutation Database (MGMD) and TransgenicDB. TransgenicDB is a comprehensive collection of transgenic rodent mutation data initially compiled and collated by Health Canada. The updated MGMD contains approximately 50 000 individual mutation spectral records from the published literature. The portal not only gives access to an enormous quantity of genetic toxicology data, but also provides statistical tools for dose-response analysis and calculation of benchmark dose. Two important R packages for dose-response analysis are provided as web-distributed applications with user-friendly graphical interfaces. The 'drsmooth' package performs dose-response shape analysis and determines various points of departure (PoD) metrics and the 'PROAST' package provides algorithms for dose-response modelling. The MutAIT statistical tools, which are currently being enhanced, provide users with an efficient and comprehensive platform to conduct quantitative dose-response analyses and determine PoD values that can then be used to calculate human exposure limits or margins of exposure. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmaco-toxicological study of diterpenoids.

PubMed

Delporte, Carla; Backhouse, Nadine; Salinas, Pedro; San-Martín, Aurelio; Bórquez, Jorge; Loyola, Alberto

2003-04-03

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

The Draft Toxicological Review was developed to evaluate both the cancer and non cancer human health risks from environmental exposure to vinyl chloride. A reference concentration (RfC), and a reference dose (RfD) were developed based upon induction of liver cell polymorphism in a chronic dietary study utilizing Wistar rats. An RfC of 1E-1 mg/m3 and an RfD of 5E-3 mg/kg-d are recommended. On the basis of sufficient evidence for carcinogenicity in human epidemiology studies vinyl chloride is reaffirmed to be a known human carcinogen. Cancer potencies were derived for oral and inhalation exposure. An oral slope factor of 1.3 per (mg/kg-day) for continuous exposure during adulthood and 2.5 per (mg/kg-day) for continuous lifetime exposure from birth, based upon a chronic dietary study in female Wistar rats is recommended; an inhalation unit risk of 4.3 E-6 per (55g/m3) for continuous exposure during adulthood and 8.7 E-6 per (55g/m3) for continuous lifetime exposure from birth is also recommended, based upon exposure of male and female Sprague Dawley rats and Swiss mice, via inhalation, for a lifetime. A PBPK model was used in the derivation of the RfC, RfD, and cancer potency estimates. Its use is based on the assumption that equal tissue concentrations of reactive metabolite, chlorethylene oxide or chloracetaldehyde, at the critical target site will result in equivalent toxicity between species.

Urinary trichloroacetic acid levels and semen quality: A hospital-based cross-sectional study in Wuhan, China

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

Xie, Shao-Hua; The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Li, Yu-Feng

Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured withmore » the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20 million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1) {mu}g/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence of the relationship between decreased sperm motility and increased urinary TCAA levels. The effect of exposure to DBPs on human male reproductive health in Chinese populations still warrants further investigations. - Research highlights: {yields} No association between DBPs exposure and semen quality was found. {yields} Effects of DBPs exposure on male reproductive health need further investigations. {yields} Intra-individual variability of urinary TCAA should be considered in the future.« less

Advancing alternatives analysis: The role of predictive toxicology in selecting safer chemical products and processes.

PubMed

Malloy, Timothy; Zaunbrecher, Virginia; Beryt, Elizabeth; Judson, Richard; Tice, Raymond; Allard, Patrick; Blake, Ann; Cote, Ila; Godwin, Hilary; Heine, Lauren; Kerzic, Patrick; Kostal, Jakub; Marchant, Gary; McPartland, Jennifer; Moran, Kelly; Nel, Andre; Ogunseitan, Oladele; Rossi, Mark; Thayer, Kristina; Tickner, Joel; Whittaker, Margaret; Zarker, Ken

2017-09-01

Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in a more cost-effective manner than traditional approaches. The present article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents 4 recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA, adopting a stepwise process to employing predictive toxicology in AA beginning with prioritization of chemicals of concern, leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting transdisciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. Integr Environ Assess Manag 2017;13:915-925. © 2017 SETAC. © 2017 SETAC.

Toxicology in Asia--Past, present, and future.

PubMed

Satoh, T

2015-12-01

The Asian Society of Toxicology (ASIATOX), which consists of the seven national toxicology member societies of Japan, Korea, China, Taiwan, Thailand, Singapore, and Iran, now boasts of more than 3,000 members from a variety of industries, academia, and regulatory organizations. ASIATOX congresses are spaced three years apart and rotated among the member societies. In 1995, ASIATOX joined the International Union of Toxicology (IUTOX) as a regional society, and now serves as the scientific voice of toxicology in Asia under the IUTOX umbrella. Since its inauguration, the society has worked diligently to handle matters deemed essential to promoting the vision set fourth by its founders. Future perspectives of ASIATOX include the establishment of education and training programs, and the certification and accreditation of toxicologists. As the leading voice of toxicology in Asia, the society seeks to extend knowledge of toxicological issues to developing nations in Asia based on the following missions and goals: (1) to provide leadership as a worldwide scientific organization that objectively addresses global issues involving the toxicological sciences, (2) to broaden the geographical base of toxicology as a discipline and profession to all countries of the world, and (3) to pursue capacity building in toxicology, particularly in developing countries, while utilizing its global perspective and network to contribute to the enhancement of toxicology education and the career development of young toxicologists. © The Author(s) 2015.

ACToR A Aggregated Computational Toxicology Resource

EPA Science Inventory

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

ACToR A Aggregated Computational Toxicology Resource (S)

EPA Science Inventory

We are developing the ACToR system (Aggregated Computational Toxicology Resource) to serve as a repository for a variety of types of chemical, biological and toxicological data that can be used for predictive modeling of chemical toxicology.

The Emergence of Systematic Review in Toxicology

PubMed Central

Stephens, Martin L.; Betts, Kellyn; Beck, Nancy B.; Cogliano, Vincent; Dickersin, Kay; Fitzpatrick, Suzanne; Freeman, James; Gray, George; Hartung, Thomas; McPartland, Jennifer; Rooney, Andrew A.; Scherer, Roberta W.; Verloo, Didier; Hoffmann, Sebastian

2016-01-01

The Evidence-based Toxicology Collaboration hosted a workshop on “The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology,” on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, historical antecedents in both medicine and toxicology, challenges to the translation of systematic review from medicine to toxicology, and thoughts on the way forward. We conclude with a recommendation that as various agencies and organizations adapt systematic review methods, they continue to work together to ensure that there is a harmonized process for how the basic elements of systematic review methods are applied in toxicology. PMID:27208075

Emerging approaches in predictive toxicology.

PubMed

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

2014-12-01

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. © 2014 Wiley Periodicals, Inc.

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

Africa's present and future needs in toxicology education: Southern African perspective

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

Gulumian, Mary; Ginsburg, Carren; Stewart, Michael J.

2005-09-01

Degrees and diplomas as well as certificates that are granted by universities and technikons in South Africa in scientific disciplines, such as forensic medicine, pharmacology, marine and veterinary sciences, environmental health, and occupational hygiene, include toxicology as one of the subjects in their overall syllabus. However, aspects of toxicology included in each of these courses are biased towards that particular subdiscipline and basic level of toxicology may be taught. Educational needs in toxicology in South Africa can be summarized as follows: (a) recognition of toxicology as a discipline in its own right at these tertiary education institutions and (b) creationmore » of opportunities to study and obtain higher degrees in one or more of the many subdisciplines of toxicology. The results from a survey conducted on the toxicology syllabi offered at these tertiary education institutions are used to substantiate these needs.« less

Moving beyond a descriptive aquatic toxicology: the value of biological process and trait information.

PubMed

Segner, Helmut

2011-10-01

In order to improve the ability to link chemical exposure to toxicological and ecological effects, aquatic toxicology will have to move from observing what chemical concentrations induce adverse effects to more explanatory approaches, that are concepts which build on knowledge of biological processes and pathways leading from exposure to adverse effects, as well as on knowledge on stressor vulnerability as given by the genetic, physiological and ecological (e.g., life history) traits of biota. Developing aquatic toxicology in this direction faces a number of challenges, including (i) taking into account species differences in toxicant responses on the basis of the evolutionarily developed diversity of phenotypic vulnerability to environmental stressors, (ii) utilizing diversified biological response profiles to serve as biological read across for prioritizing chemicals, categorizing them according to modes of action, and for guiding targeted toxicity evaluation; (iii) prediction of ecological consequences of toxic exposure from knowledge of how biological processes and phenotypic traits lead to effect propagation across the levels of biological hierarchy; and (iv) the search for concepts to assess the cumulative impact of multiple stressors. An underlying theme in these challenges is that, in addition to the question of what the chemical does to the biological receptor, we should give increasing emphasis to the question how the biological receptor handles the chemicals, i.e., through which pathways the initial chemical-biological interaction extends to the adverse effects, how this extension is modulated by adaptive or compensatory processes as well as by phenotypic traits of the biological receptor. 2011 Elsevier B.V. All rights reserved.

The SPOTS System: An Ocular Scoring System Optimized for Use in Modern Preclinical Drug Development and Toxicology.

PubMed

Eaton, Joshua Seth; Miller, Paul E; Bentley, Ellison; Thomasy, Sara M; Murphy, Christopher J

2017-12-01

To present a semiquantitative ocular scoring system comprising elements and criteria that address many of the limitations associated with systems commonly used in preclinical studies, providing enhanced cross-species applicability and predictive value in modern ocular drug and device development. Revisions to the ocular scoring systems of McDonald-Shadduck and Hackett-McDonald were conducted by board-certified veterinary ophthalmologists at Ocular Services On Demand (OSOD) over the execution of hundreds of in vivo preclinical ocular drug and device development studies and general toxicological investigations. This semiquantitative preclinical ocular toxicology scoring (SPOTS) system was driven by limitations of previously published systems identified by our group's recent review of slit lamp-based scoring systems in clinical ophthalmology, toxicology, and vision science. The SPOTS system provides scoring criteria for the anterior segment, posterior segment, and characterization of intravitreal test articles. Key elements include: standardized slit lamp settings; expansion of criteria to enhance applicability to nonrabbit species; refinement and disambiguation of scoring criteria for corneal opacity, fluorescein staining severity, and aqueous flare; introduction of novel criteria for scoring of aqueous and anterior vitreous cell; and introduction of criteria for findings observed with drugs/devices targeting the posterior segment. A modified Standardization of Uveitis Nomenclature (SUN) system is also introduced to facilitate accurate use of SUN's criteria in laboratory species. The SPOTS systems provide criteria that stand to enhance the applicability of semiquantitative scoring criteria to the full range of laboratory species, in the context of modern approaches to ocular therapeutics and drug delivery and drug and device development.

The concentration of no toxicologic concern (CoNTC) and airborne mycotoxins.

PubMed

Hardin, Bryan D; Robbins, Coreen A; Fallah, Payam; Kelman, Bruce J

2009-01-01

The threshold of toxicologic concern (TTC) concept was developed as a method to identify a chemical intake level that is predicted to be without adverse human health effects assuming daily intake over the course of a 70-yr life span. The TTC values are based on known structure-activity relationships and do not require chemical-specific toxicity data. This allows safety assessment (or prioritization for testing) of chemicals with known molecular structure but little or no toxicity data. Recently, the TTC concept was extended to inhaled substances by converting a TTC expressed in micrograms per person per day to an airborne concentration (ng/m(3)), making allowance for intake by routes in addition to inhalation and implicitly assuming 100% bioavailability of inhaled toxicants. The resulting concentration of no toxicologic concern (CoNTC), 30 ng/m(3), represents a generic airborne concentration that is expected to pose no hazard to humans exposed continuously throughout a 70-yr lifetime. Published data on the levels of mycotoxins in agricultural dusts or in fungal spores, along with measured levels of airborne mycotoxins, spores, or dust in various environments, were used to identify conditions under which mycotoxin exposures might reach the CoNTC. Data demonstrate that airborne concentrations of dusts and mold spores sometimes encountered in agricultural environments have the potential to produce mycotoxin concentrations greater than the CoNTC. On the other hand, these data suggest that common exposures to mycotoxins from airborne molds in daily life, including in the built indoor environment, are below the concentration of no toxicologic concern.

Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry.

PubMed

Grapp, Marcel; Kaufmann, Christoph; Streit, Frank; Binder, Lutz

2018-06-01

Comprehensive screening procedures for psychoactive agents in body fluids are an essential task in clinical and forensic toxicology. With the continuous emergence and adaption of new psychoactive substances (NPS) keeping a screening method up to date is challenging. To meet these demands, hyphenated high-resolution mass spectrometry has gained interest as extensive and expandable screening approach. Here we present a comprehensive method for systematic toxicological analysis of serum by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) with data independent acquisition. The potential of this method was demonstrated by analysis of 247 authentic serum- and 12 post-mortem femoral blood samples. Thus 950 compounds, comprising 185 different drugs and metabolites could be identified. For the detected substances, including pharmaceutical substances, illicit drugs as well as NPS, serum concentrations were confirmed ranging from traces to toxic values indicating the capability for forensic toxicological requirements. Positive identification of drugs was achieved by accurate mass measurement (±5ppm for [M+H] + ; ±10ppm for [M-H] - ), retention time (±0.35min), isotopic pattern match (less than 10 m/z RMS [ppm]), isotope match intensity (less than 20% RMS) and the presence of at least two fragment ions. The LC-QTOF-MS procedure was shown to be superior to serum screening by GC-MS, since 240% (335 versus 141) more drugs were identified in serum samples compared to GC-MS. Copyright © 2018 Elsevier B.V. All rights reserved.

Space X First Entry Sample Analysis

NASA Technical Reports Server (NTRS)

James, John T.

2012-01-01

The toxicological assessment of one sample collected on May 26, 2012 and returned to earth on May 31, 2012 was analyzed for pollutants that had offgassed into the Dragon capsule by the time of first entry operations performed by the ISS crew. The components identified in the first-entry sample and their contributions to the total T-value are shown.

[Clinical toxicology of the Academy: yesterday, today and tomorrow].

PubMed

Sofronov, G A; Khalimov, Iu Sh; Matveev, S Iu; Kuz'mich, V G; Fomichev, A V

2013-12-01

National toxicology school of the Kirov Military Medical Academy, demonstrates the unity of clinical and experimental approaches related to one purpose throughout its history--saving human life and health from exposure to toxic substances of chemical nature. For more than three centuries the russian science of toxicology has been steadily developing, often ahead of the world science. It helped to create the means of protection and develop methods of treatment for chemical lesions. Currently, toxicology departments of military field therapy and military toxicology and medical protection are actively involved in the current study of military medicine, restructuring policy to provide toxicological aid in the Armed Forces, the development and introduction of Innovative methods of diagnosis and treatment of victims of toxicological etiology.

TOXNET (TOXICOLOGY DATA NETWORK)

EPA Science Inventory

TOXNET (Toxicology Data Network) is a computerized system of files oriented to toxicology and related areas. It is managed by the National Library of Medicines Toxicology and Environmental Health Information Program (TEHIP) and runs on a series of microcomputers in a networked cl...

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 488

NASA Technical Reports Server (NTRS)

1999-01-01

This report lists reports, articles and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 107, October 1972

NASA Technical Reports Server (NTRS)

1972-01-01

This Supplement of Aerospace Medicine and Biology lists 353 reports, articles, and other documents announced during September 1972 in Scientific and Technical Aerospace Reports or in International Aerospace Abstracts. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Graduate Training in Toxicology in Colleges of Veterinary Medicine.

ERIC Educational Resources Information Center

Robens, J. F.; Buck, W. B.

1979-01-01

Presented are an American Board of Veterinary Toxicology survey and evaluation of the training resources available in graduate programs in toxicology located in colleges of veterinary medicine. Regulatory toxicology, number of toxicologists needed, and curriculum are also discussed. (JMD)

Regulatory issues in accreditation of toxicology laboratories.

PubMed

Bissell, Michael G

2012-09-01

Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Mapping the Human Toxome by Systems Toxicology

PubMed Central

Bouhifd, Mounir; Hogberg, Helena T.; Kleensang, Andre; Maertens, Alexandra; Zhao, Liang; Hartung, Thomas

2014-01-01

Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which human beings are potentially exposed whose potential toxicity remains largely unknown. Employing new testing strategies that employ the use of predictive, high-throughput cell-based assays (of human origin) to evaluate perturbations in key pathways, referred as pathways of toxicity, and to conduct targeted testing against those pathways, we can begin to greatly accelerate our ability to test the vast “storehouses” of chemical compounds using a rational, risk-based approach to chemical prioritization, and provide test results that are more predictive of human toxicity than current methods. The NIH Transformative Research Grant project Mapping the Human Toxome by Systems Toxicology aims at developing the tools for pathway mapping, annotation and validation as well as the respective knowledge base to share this information. PMID:24443875

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

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

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 providesmore » 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.« less

[Assessment of so called organic trace compounds in drinking water from the regulatory, health and aesthetic-quality points of view, with special consideration given to pharmaceuticals].

PubMed

Dieter, H H; Mückter, H

2007-03-01

More than 2500 chemically defined substances are approved as drugs in Germany. Unlike agricultural pesticides, these biologically active structures are not used in open environmental compartments and therefore their environmental toxicological data base is not nearly as complete. Nevertheless, some of them become environmental contaminants after their intended use. Therefore, from the viewpoint of environmental health protection, there are gaps in their health-related environmental risk assessment. Organic trace compounds that lack an adequate toxicological database, and their mixtures, in drinking water can be safely regulated and provisionally assessed by combining the "similar joint action" addition rule with the recommendation of the Federal Environment Agency of March 2003 "Assessing the presence of substances in drinking water without (adequate) toxicological database from the health point of view". The general precautionary value (Gesundheitlicher Orientierungswert GOW1=0.10 microg/l), which is a recommendation for weakly to not genotoxic compounds, re presents a workable compromise between preventive health protection, water management considerations and aesthetic quality claims (purity). Compliance with this value in the long term will only be possible if the chemical and biological degradation of pharmaceuticals and their metabolites in waste water and waste water treatment plants is effectively improved. Alternatively, there is the risk of drinking water degenerating into a sink for highly mobile, polar and persistent compounds. Their elimination at a stage as late as technical drinking water treatment would be neither close to the initial cause nor justifiable in terms of technical effectiveness. The risk assessment of their byproducts would give rise to further uncertainties. Possible conflicts with the therapeutic quality must be solved by developing substitute products which are environmentally sound.

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, the...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 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, the...

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, the...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 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, the...

42 CFR 493.1213 - Condition: Toxicology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 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, the...

Identification of suitable qPCR reference genes in leaves of Brassica oleracea under abiotic stresses.

PubMed

Brulle, Franck; Bernard, Fabien; Vandenbulcke, Franck; Cuny, Damien; Dumez, Sylvain

2014-04-01

Real-time quantitative PCR is nowadays a standard method to study gene expression variations in various samples and experimental conditions. However, to interpret results accurately, data normalization with appropriate reference genes appears to be crucial. The present study describes the identification and the validation of suitable reference genes in Brassica oleracea leaves. Expression stability of eight candidates was tested following drought and cold abiotic stresses by using three different softwares (BestKeeper, NormFinder and geNorm). Four genes (BolC.TUB6, BolC.SAND1, BolC.UBQ2 and BolC.TBP1) emerged as the most stable across the tested conditions. Further gene expression analysis of a drought- and a cold-responsive gene (BolC.DREB2A and BolC.ELIP, respectively), confirmed the stability and the reliability of the identified reference genes when used for normalization in the leaves of B. oleracea. These four genes were finally tested upon a benzene exposure and all appeared to be useful reference genes along this toxicological condition. These results provide a good starting point for future studies involving gene expression measurement on leaves of B. oleracea exposed to environmental modifications.

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 139

NASA Technical Reports Server (NTRS)

1975-01-01

The biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space are referenced. Similar effects on biological organisms of lower order are also included. Related topics such as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors are discussed. Applied research is emphasized, but references to fundamental studies and theoretical principles related to experimental development are also included. A total of 242 reports, articles, and other documents are listed.

Hamilton and Hardy for the 21st Century

PubMed Central

Ogden, Trevor

2016-01-01

Hamilton and Hardy’s Industrial Toxicology is now 80 years old, and the new sixth edition links us with a pioneer era. This is an impressive book, but the usefulness of the hardback version as a reference book is unfortunately limited by its poor index. There is now an ebook version, and for the practitioner on the move this has the great advantages of searchability and portability. However, Wiley ebooks can apparently only be downloaded when first purchased, so their lifetime is limited to that of the device. The Kindle edition should avoid this shortcoming.

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

PubMed

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

1980-03-01

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

77 FR 40358 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... Alternative Toxicological Methods (SACATM) AGENCY: Division of the National Toxicology Program (DNTP.../live ). SACATM advises the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM...

[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.

Mass Spectrometry Applications for Toxicology

PubMed Central

Mbughuni, Michael M.; Jannetto, Paul J.

2016-01-01

Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

Essential and toxic element concentrations in blood and urine and their associations with diet: results from a Norwegian population study including high-consumers of seafood and game.

PubMed

Birgisdottir, B E; Knutsen, H K; Haugen, M; Gjelstad, I M; Jenssen, M T S; Ellingsen, D G; Thomassen, Y; Alexander, J; Meltzer, H M; Brantsæter, A L

2013-10-01

The first aim of the study was to evaluate calculated dietary intake and concentrations measured in blood or urine of essential and toxic elements in relation to nutritional and toxicological reference values. The second aim was to identify patterns of the element concentrations in blood and urine and to identify possible dietary determinants of the concentrations of these elements. Adults with a known high consumption of environmental contaminants (n=111), and a random sample of controls (n=76) answered a validated food frequency questionnaire (FFQ). Complete data on biological measures were available for 179 individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic, mercury, cadmium and lead. Principal component analysis was used to identify underlying patterns of correlated blood and urine concentrations. The calculated intakes of selenium, iodine, inorganic arsenic and mercury were within guideline levels. For cadmium 24% of the high consumer group and 8% of the control group had intakes above the tolerable weekly intake. Concentrations of lead in blood exceeded the bench-mark dose lower confidence limits for some participants. However, overall, the examined exposures did not give rise to nutritional or toxicological concerns. Game consumption was associated with lead in blood (B(ln) 0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015). A novel finding was a distinct pattern of positively associated biological markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8), reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly demonstrates the significance of seafood as a source of both essential nutrients and toxic elements simultaneously and shows that exposure to various essential and toxic elements can be intertwined. © 2013 Elsevier B.V. All rights reserved.

Reaching Nutritional Adequacy Does Not Necessarily Increase Exposure to Food Contaminants: Evidence from a Whole-Diet Modeling Approach.

PubMed

Barré, Tangui; Vieux, Florent; Perignon, Marlène; Cravedi, Jean-Pierre; Amiot, Marie-Josèphe; Micard, Valérie; Darmon, Nicole

2016-10-01

Dietary guidelines are designed to help meet nutritional requirements, but they do not explicitly or quantitatively account for food contaminant exposures. In this study, we aimed to test whether dietary changes needed to achieve nutritional adequacy were compatible with acceptable exposure to food contaminants. Data from the French national dietary survey were linked with food contaminant data from the French Total Diet Study to estimate the mean intake of 204 representative food items and mean exposure to 27 contaminants, including pesticides, heavy metals, mycotoxins, nondioxin-like polychlorinated biphenyls (NDL-PCBs) and dioxin-like compounds. For each sex, 2 modeled diets that departed the least from the observed diet were designed: 1) a diet respecting only nutritional recommendations (NUT model), and 2) a diet that met nutritional recommendations without exceeding Toxicological Reference Values (TRVs) and observed contaminant exposures (NUTOX model). Food, nutrient, and contaminant contents in observed diets and NUT and NUTOX diets were compared with the use of paired t tests. Mean observed diets did not meet all nutritional recommendations, but no contaminant was over 48% of its TRV. Achieving all the nutrient recommendations through the NUT model mainly required increases in fruit, vegetable, and fish intake and decreases in meat, cheese, and animal fat intake. These changes were associated with significantly increased dietary exposure to some contaminants, but without exceeding 57% of TRVs. The highest increases were found for NDL-PCBs (from 26% to 57% of TRV for women). Reaching nutritional adequacy without exceeding observed contaminant exposure (NUTOX model) was possible but required further departure from observed food quantities. Based on a broad range of nutrients and contaminants, this first assessment of compatibility between nutritional adequacy and toxicological exposure showed that reaching nutritional adequacy might increase exposure to food contaminants, but within tolerable levels. However, there are some food combinations that can meet nutritional recommendations without exceeding observed exposures. © 2016 American Society for Nutrition.

A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

PubMed Central

Slob, Wout

2015-01-01

Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Results Probabilistically derived exposure limits are based on estimating a “target human dose” (HDMI), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes. Conclusions Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions. Citation Chiu WA, Slob W. 2015. A unified probabilistic framework for dose–response assessment of human health effects. Environ Health Perspect 123:1241–1254; http://dx.doi.org/10.1289/ehp.1409385 PMID:26006063

Historical milestones and discoveries that shaped the toxicology sciences.

PubMed

Hayes, Antoinette N; Gilbert, Steven G

2009-01-01

Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages, toxicological science has provided information that has shaped and guided society. This chapter examines the development of the discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This chapter also examines how toxicology and the toxicologist have interacted with other scientific and cultural disciplines, including religion, politics, and the government. Toxicology has evolved to a true scientific discipline with its own dedicated scientists, educational institutes, sub-disciplines, professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, pharmacology, and molecular biology. We invite you to join us on a path of discovery and to offer our suggestions as to what are the most significant milestones and discoveries in toxicology. Additional information is available on the history section of Toxipedia (www.toxipedia.org).

76 FR 23323 - Meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... Alternative Toxicological Methods (SACATM) AGENCY: National Toxicology Program (NTP), National Institute of... the Validation of Alternative Methods (ICCVAM), the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), and the Director of the NIEHS and NTP regarding statutorily...

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)

TOXNET and Beyond: Using the National Library of Medicine's Environmental Health and Toxicology Portal

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

Templin-Branner, W.

2010-10-20

The National Library of Medicine's Environmental Health and Toxicology Portal provides access to numerous databases that can help you explore environmental chemicals and risks. TOXNET and Beyond: Using NLM's Environmental Health and Toxicology Portal conveys the fundamentals of searching the NLM's TOXNET system of databases in chemistry, toxicology, environmental health, and related fields. In addition to TOXNET, the course will highlight various resources available through the Environmental Health and Toxicology Portal.

Overview of Forensic Toxicology, Yesterday, Today and in the Future.

PubMed

Chung, Heesun; Choe, Sanggil

2017-01-01

The scope of forensic toxicology has been tremendously expanded over the past 50 years. From two general sections forensic toxicology can be further classified into 8-9 sections. The most outstanding improvement in forensic toxicology is the changes brought by instrumental development. The field of forensic toxicology was revolutionized by the development of immunoassay and benchtop GC-MS in the 1980's and LC-MS-MS in 2000's. Detection of trace amounts of analytes has allowed the use of new specimens such as hair and oral fluids, along with blood and urine. Over a longer period of time, continuous efforts have been made to efficiently extract and separate drug and poison from biological fluids. International endeavors to develop high quality standards and guidelines for drugs and poisons in biological specimens and to promote them in order to increase reliability of laboratories are also part of the recent advancement of forensic toxicology. Interpretation of postmortem toxicology encompasses various factors including postmortem redistribution and stability. Considering the recent trend, the interpretation of toxicological results should account for autopsy findings, crime scene information, and related medical history. The fields of forensic toxicology will continuously develop to improve analysis of target analytes from various specimens, quality assurance program, and results interpretation. In addition, the development of analytical techniques will also contribute further advancement of forensic toxicology. The societies of forensic toxicologists, such as TIAFT, will play an important role for the advancement of forensic toxicology by collaborating and sharing ideas between toxicologists from both developed and developing countries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Personal digital assistant applications for the healthcare provider.

PubMed

Keplar, Kristine E; Urbanski, Christopher J

2003-02-01

To review some common medical applications available for personal digital assistants (PDAs), with brief discussion of the different PDA operating systems and memory requirements. Key search terms included handheld, PDA, personal digital assistants, and medical applications. The literature was accessed through MEDLINE (1999-August 2002). Other information was obtained through secondary sources such as Web sites describing common PDAs. Medical applications available on PDAs are numerous and include general drug references, specialized drug references (e.g., pediatrics, geriatrics, cardiology, infectious disease), diagnostic guides, medical calculators, herbal medication references, nursing references, toxicology references, and patient tracking databases. Costs and memory requirements for these programs can vary; consequently, the healthcare provider must limit the medication applications that are placed on the handheld computer. This article attempts to systematically describe the common medical applications available for the handheld computer along with cost, memory and download requirements, and Web site information. This review found many excellent PDA drug information applications offering many features which will aid the healthcare provider. Very likely, after using these PDA applications, the healthcare provider will find them indispensable, as their multifunctional capabilities can save time, improve accuracy, and allow for general business procedures as well as being a quick reference tool. To avoid the benefits of this technology might be a step backward.

Health risk assessment of organic micropollutants in greywater for potable reuse.

PubMed

Etchepare, Ramiro; van der Hoek, Jan Peter

2015-04-01

In light of the increasing interest in development of sustainable potable reuse systems, additional research is needed to elucidate the risks of producing drinking water from new raw water sources. This article investigates the presence and potential health risks of organic micropollutants in greywater, a potential new source for potable water production introduced in this work. An extensive literature survey reveals that almost 280 organic micropollutants have been detected in greywater. A three-tiered approach is applied for the preliminary health risk assessment of these chemicals. Benchmark values are derived from established drinking water standards for compounds grouped in Tier 1, from literature toxicological data for compounds in Tier 2, and from a Threshold of Toxicological Concern approach for compounds in Tier 3. A risk quotient is estimated by comparing the maximum concentration levels reported in greywater to the benchmark values. The results show that for the majority of compounds, risk quotient values were below 0.2, which suggests they would not pose appreciable concern to human health over a lifetime exposure to potable water. Fourteen compounds were identified with risk quotients above 0.2 which may warrant further investigation if greywater is used as a source for potable reuse. The present findings are helpful in prioritizing upcoming greywater quality monitoring and defining the goals of multiple barriers treatment in future water reclamation plants for potable water production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space.

PubMed

Yang, Chihae; Barlow, Susan M; Muldoon Jacobs, Kristi L; Vitcheva, Vessela; Boobis, Alan R; Felter, Susan P; Arvidson, Kirk B; Keller, Detlef; Cronin, Mark T D; Enoch, Steven; Worth, Andrew; Hollnagel, Heli M

2017-11-01

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

PubMed

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

PubMed

Contrera, Joseph F

2011-02-01

The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values. Copyright © 2010 Elsevier Inc. All rights reserved.

Fundamentals of translational neuroscience in toxicologic pathology: optimizing the value of animal data for human risk assessment.

PubMed

Morrison, James P; Sharma, Alok K; Rao, Deepa; Pardo, Ingrid D; Garman, Robert H; Kaufmann, Wolfgang; Bolon, Brad

2015-01-01

A half-day Society of Toxicologic Pathology continuing education course on "Fundamentals of Translational Neuroscience in Toxicologic Pathology" presented some current major issues faced when extrapolating animal data regarding potential neurological consequences to assess potential human outcomes. Two talks reviewed functional-structural correlates in rodent and nonrodent mammalian brains needed to predict behavioral consequences of morphologic changes in discrete neural cell populations. The third lecture described practical steps for ensuring that specimens from rodent developmental neurotoxicity tests will be processed correctly to produce highly homologous sections. The fourth talk detailed demographic factors (e.g., species, strain, sex, and age); physiological traits (body composition, brain circulation, pharmacokinetic/pharmacodynamic patterns, etc.); and husbandry influences (e.g., group housing) known to alter the effects of neuroactive agents. The last presentation discussed the appearance, unknown functional effects, and potential relevance to humans of polyethylene glycol (PEG)-associated vacuoles within the choroid plexus epithelium of animals. Speakers provided real-world examples of challenges with data extrapolation among species or with study design considerations that may impact the interpretability of results. Translational neuroscience will be bolstered in the future as less invasive and/or more quantitative techniques are devised for linking overt functional deficits to subtle anatomic and chemical lesions. © 2014 by The Author(s).

Which level of evidence does the US National Toxicology Program provide? Statistical considerations using the Technical Report 578 on Ginkgo biloba as an example.

PubMed

Gaus, Wilhelm

2014-09-02

The US National Toxicology Program (NTP) is assessed by a statistician. In the NTP-program groups of rodents are fed for a certain period of time with different doses of the substance that is being investigated. Then the animals are sacrificed and all organs are examined pathologically. Such an investigation facilitates many statistical tests. Technical Report TR 578 on Ginkgo biloba is used as an example. More than 4800 statistical tests are possible with the investigations performed. Due to a thought experiment we expect >240 false significant tests. In actuality, 209 significant pathological findings were reported. The readers of Toxicology Letters should carefully distinguish between confirmative and explorative statistics. A confirmative interpretation of a significant test rejects the null-hypothesis and delivers "statistical proof". It is only allowed if (i) a precise hypothesis was established independently from the data used for the test and (ii) the computed p-values are adjusted for multiple testing if more than one test was performed. Otherwise an explorative interpretation generates a hypothesis. We conclude that NTP-reports - including TR 578 on Ginkgo biloba - deliver explorative statistics, i.e. they generate hypotheses, but do not prove them. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

NLM Web Resources for Environmental Health and Biomedical Research

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

Foster, R.

2010-09-12

The National Library of Medicine (NLM) is sponsoring this course to increase awareness of the availability and value of NLM’s online environmental health and toxicology information resources that provide invaluable tools to address these issues—for professionals and consumers alike. Participants will receive hands-on practice with selected NLM resources, and demonstrations of other valuable resources will be provided.

A Partial Exploration of the Potential Energy Surfaces of SCN and HSCN: Implications for the Enzyme-Mediated Detoxification of Cyanide

DTIC Science & Technology

2009-01-01

its role in toxicology , Tox. Sci. 78 (2004) 185–188. [6] (a) B.H. Sorbo, Crystalline rhodanese. I. Purification and physicochemical exam- ination, Acta...the devel- opment of quantitative structure–activity relationships ( QSARs ). pKa-values of phenols and aromatic and aliphatic carboxylic acids, Chemosphere 19 (1989) 1595.

Measurement of Libby Amphibole (LA) Elongated Particle Dissolution Rates and Alteration of Size/Shape Distributions in Support of Human Dosimetry Model Development and Relative Potency Determinations

EPA Science Inventory

To maximize the value of toxicological data in development of human health risk assessment models of inhaled elongated mineral particles, improvements in human dosimetry modeling are needed. In order to extend the dosimetry model of deposited fibers (Asgharian et aI., Johnson 201...

Harold Seifried, PhD | Division of Cancer Prevention

Cancer.gov

Dr. Harold Seifried is a member of the American Chemical Society Biological Chemistry Division; American College of Toxicology Industrial Toxicology Subcommittee; American Industrial Hygiene Association; Society of Toxicology; International Society for the Study of Xenobiotics; Diplomate of the American Board of Toxicology since 1980; American Board of Industrial Hygiene,

40 CFR 159.165 - Toxicological and ecological studies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Toxicological and ecological studies... Information § 159.165 Toxicological and ecological studies. Adverse effects information must be submitted as follows: (a) Toxicological studies. (1) The results of a study of the toxicity of a pesticide to humans or...

40 CFR 159.165 - Toxicological and ecological studies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxicological and ecological studies... Information § 159.165 Toxicological and ecological studies. Adverse effects information must be submitted as follows: (a) Toxicological studies. (1) The results of a study of the toxicity of a pesticide to humans or...

Society of Toxicologic Pathologists (STP) Annual Symposium General Session II: Modem Pathology Methods for Neural Investigations

EPA Science Inventory

This half-day session at the 20I0 Joint Symposium of the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP) explored many deceptively simple questions related to toxicologic neuropathology. What is the best met...

The limits of regulatory toxicology

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

Carrington, Clark D.; Bolger, P. Michael, E-mail: mike.bolger@fda.hhs.go

2010-03-01

The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standardsmore » are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.« less

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

Is contaminated unrecorded alcohol a health problem in the European Union? A review of existing and methodological outline for future studies.

PubMed

Lachenmeier, Dirk W; Schoeberl, Kerstin; Kanteres, Fotis; Kuballa, Thomas; Sohnius, Eva-Maria; Rehm, Jürgen

2011-03-01

Some European countries with high levels of unrecorded alcohol consumption have anomalously high rates of death attributable to liver cirrhosis. Hepatotoxic compounds in illegally produced spirits may be partly responsible. Based on a review of the evidence on the chemical composition and potential harm from unrecorded alcohol, the Alcohol Measures for Public Health Research Alliance (AMPHORA) project's methodology for identifying, analysing and toxicologically evaluating such alcohols is provided. A computer-assisted literature review concentrated on unrecorded alcohol. Additionally, we refer to our work in the capacity of governmental alcohol control authority and a number of pilot studies. The risk-oriented identification of substances resulted in the following compounds probably posing a public health risk in unrecorded alcohol: ethanol, methanol, acetaldehyde, higher alcohols, heavy metals, ethyl carbamate, biologically active flavourings (e.g. coumarin) and diethyl phthalate. Suggestions on a sampling strategy for identifying unrecorded alcohol that may be most prone to contamination include using probable distribution points such as local farmers and flea markets for selling surrogate alcohol (including denatured alcohol) to focusing on lower socio-economic status or alcohol-dependent individuals, and selecting home-produced fruit spirits prone to ethyl carbamate contamination. Standardized guidelines for the chemical and toxicological evaluation of unrecorded alcohol that will be used in a European-wide sampling and are applicable globally are provided. These toxicological guidelines may also be used by alcohol control laboratories for recorded alcohol products, and form a scientific foundation for establishing legislative limits. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

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

Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the toxicological detection of PPP and 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP) studied in rat urine using gas chromatography-mass spectrometry.

PubMed

Springer, Dietmar; Fritschi, Giselher; Maurer, Hans H

2003-11-05

R,S-alpha-pyrrolidinopropiophenone (PPP) is a new designer drug with assumed amphetamine-like effects which has appeared on the illicit drug market. The aim of this study was to identify the PPP metabolites using solid-phase extraction, ethylation or acetylation as well as to develop a toxicological detection procedure in urine using solid-phase extraction, trimethylsilylation and gas chromatography-mass spectrometry (GC-MS). Analysis of urine samples of rats treated with PPP revealed that PPP was extensively metabolized by hydroxylation of the pyrrolidine ring with subsequent dehydrogenation to the corresponding lactam, hydroxylation of the aromatic ring in position 4' or double dealkylation of the pyrrolidine ring to the corresponding primary amine (cathinone) partly followed by reduction of the keto group to the corresponding secondary alcohol (norephedrines). As cathinone and the norephedrine diastereomers are also formed after intake of other drugs of abuse or medicaments, special attention must be paid to the detection of the unequivocal metabolite 2"-oxo-PPP as an unambiguous proof for the intake of PPP. The hydroxy groups were found to be partly conjugated. Based on these data, PPP could be detected in urine via its metabolites by full-scan GC-MS using mass chromatography for screening and library search for identification by comparison of the spectra with reference spectra. The same toxicological detection procedure can be applied to other designer drugs of the pyrrolidinophenone type, like MOPPP, MDPPP, MPHP, and MPPP. The detection of the latter will also be presented here.

THE INFLUENCE OF GLOBAL CLIMATE CHANGE ON THE SCIENTIFIC FOUNDATIONS AND APPLICATIONS OF ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY: INTRODUCTION TO A SETAC INTERNATIONAL WORKSHOP

PubMed Central

Stahl, Ralph G; Hooper, Michael J; Balbus, John M; Clements, William; Fritz, Alyce; Gouin, Todd; Helm, Roger; Hickey, Christopher; Landis, Wayne; Moe, S Jannicke

2013-01-01

This is the first of seven papers resulting from a Society of Environmental Toxicology and Chemistry (SETAC) international workshop titled “The Influence of Global Climate Change on the Scientific Foundations and Applications of Environmental Toxicology and Chemistry.” The workshop involved 36 scientists from 11 countries and was designed to answer the following question: How will global climate change influence the environmental impacts of chemicals and other stressors and the way we assess and manage them in the environment? While more detail is found in the complete series of articles, some key consensus points are as follows: (1) human actions (including mitigation of and adaptation to impacts of global climate change [GCC]) may have as much influence on the fate and distribution of chemical contaminants as does GCC, and modeled predictions should be interpreted cautiously; (2) climate change can affect the toxicity of chemicals, but chemicals can also affect how organisms acclimate to climate change; (3) effects of GCC may be slow, variable, and difficult to detect, though some populations and communities of high vulnerability may exhibit responses sooner and more dramatically than others; (4) future approaches to human and ecological risk assessments will need to incorporate multiple stressors and cumulative risks considering the wide spectrum of potential impacts stemming from GCC; and (5) baseline/reference conditions for estimating resource injury and restoration/rehabilitation will continually shift due to GCC and represent significant challenges to practitioners. Environ. Toxicol. Chem. 2013;32:13–19. © 2012 SETAC PMID:23097130

The International Union of Toxicology (IUTOX): history and its role in information on toxicology.

PubMed

Schou, Jens S; Hodel, Christian M

2003-08-21

The International Union of Toxicology (IUTOX) was founded in 1980 in Brussels. The initiative was started by the Society of Toxicology (SOT), USA, and the European Society of Toxicology in 1975 (EST), and the foundation prepared by an Inter Society Liason Committee. Eight National Societies of Toxicology were founding members of IUTOX besides SOT and EST. It now comprises 43 national/regional Societies from all over the world, representing over 20,000 toxicologists. Information has always been a key element in toxicology. Information exchange in IUTOX has evolved from letters and phone calls to fax, e-mail and the use of the Internet. Initially, newsletters were created which were mailed and later displayed on the Web. The website has been developed as a major information tool with many useful links, thereby providing information for the scientific community, the media and the lay public.

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.

PubMed

Zhang, Boyang; Huang, Kunlun; Zhu, Liye; Luo, Yunbo; Xu, Wentao

2017-07-01

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

FORUM - FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology

EPA Science Inventory

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo resp...

76 FR 36923 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of Cancellation AGENCY: National Toxicology Program (NTP), National... Toxicology Program. [FR Doc. 2011-15656 Filed 6-22-11; 8:45 am] BILLING CODE 4140-01-P ...

76 FR 10906 - Proposed Substances To Be Evaluated for Set 25 Toxicological Profiles

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

...-269] Proposed Substances To Be Evaluated for Set 25 Toxicological Profiles AGENCY: Agency for Toxic... comments on the proposed substances to be evaluated for Set 25 toxicological profiles. SUMMARY: ATSDR is initiating the development of its 25th set of toxicological profiles (CERCLA Set 25). This notice announces...

Aspects of matrix effects in applications of liquid chromatography-mass spectrometry to forensic and clinical toxicology--a review.

PubMed

Peters, Frank T; Remane, Daniela

2012-06-01

In the last decade, liquid chromatography coupled to (tandem) mass spectrometry (LC-MS(-MS)) has become a versatile technique with many routine applications in clinical and forensic toxicology. However, it is well-known that ionization in LC-MS(-MS) is prone to so-called matrix effects, i.e., alteration in response due to the presence of co-eluting compounds that may increase (ion enhancement) or reduce (ion suppression) ionization of the analyte. Since the first reports on such matrix effects, numerous papers have been published on this matter and the subject has been reviewed several times. However, none of the existing reviews has specifically addressed aspects of matrix effects of particular interest and relevance to clinical and forensic toxicology, for example matrix effects in methods for multi-analyte or systematic toxicological analysis or matrix effects in (alternative) matrices almost exclusively analyzed in clinical and forensic toxicology, for example meconium, hair, oral fluid, or decomposed samples in postmortem toxicology. This review article will therefore focus on these issues, critically discussing experiments and results of matrix effects in LC-MS(-MS) applications in clinical and forensic toxicology. Moreover, it provides guidance on performance of studies on matrix effects in LC-MS(-MS) procedures in systematic toxicological analysis and postmortem toxicology.

History of Japanese Society of Toxicology.

PubMed

Satoh, Tetsuo

2016-01-01

Founded in 1981, the Japanese Society of Toxicology (JSOT) has grown into an organization of nearly 3,000 members working together to advance the nation's scientific knowledge and understanding of toxicology through the implementation of planning that ensures a systematic and efficient expenditure of energies and resources, and is closely aligned with a strategy for accomplishing the Society's long-range plans. To promote public education in toxicology, the Society organizes public lectures during each year's annual meeting. Other activities include hosting scientific conferences, promoting continuing education, and facilitating international collaboration. Internally, the JSOT operates five standing committees: General Affairs, Educational, Editorial, Finance, and Science and Publicity to handle its necessary relationships. To bestow official recognition, the Society established its Toxicologist Certification Program in 1997, and has certified 536 members as Diplomat Toxicologists (DJSOT) as of May 1, 2016. Furthermore, on the same date, 43 JSOT members were certified as Emeritus Diplomats of the JSOT (EDJSOT). The Society has launched two official journals, the "Journal of Toxicological Sciences (JTS)" in 1981 and "Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.)" in 2014. As for participation in the international organizations, the JSOT (then known as the Toxicological Research Group) joined the International Union of Toxicology as a charter member in 1980, and became a founding member of the Asian Society of Toxicology at its inauguration in 1994. Into the future, the JSOT will continue working diligently to advance knowledge and understanding of toxicology and secure its place among the interdisciplinary fields of science, humane studies, and ethics.

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, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.

Opportunity for Collaboration Between Radiation Injury Treatment Network Centers and Medical Toxicology Specialists.

PubMed

Davlantes, Elizabeth; Shartar, Samuel; Venero, Jennifer; Steck, Alaina; Langston, Amelia; Kazzi, Ziad N

2017-08-01

The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers. We determined the locations of existing RITN centers and assessed their proximity to various medical toxicology resources, including medical toxicology fellowship programs, inpatient toxicology services, outpatient toxicology clinics, and poison control centers. Data were derived from publicly available Internet sources in March 2015. The majority of RITN centers do not have a medical toxicology fellowship, an inpatient toxicology service, or an outpatient toxicology clinic within the same institution. Fifty-seven percent of RITN centers have at least one of these resources located in the same city, however, and 73% of centers have at least one of these resources or a poison control center within the same city. Ninety-five percent of RITN centers have at least one medical toxicology resource within the state. Most RITN centers are located in the same city as at least one medical toxicology resource. Establishing relationships between RITN centers and medical toxicologists needs to be explored further.

Ethnobotanical, phytochemical and toxicological studies of Xanthium strumarium L.

PubMed

Islam, Mohammad Rashedul; Uddin, Mohammad Zashim; Rahman, Mohammad Sharifur; Tutul, Ershad; Rahman, Mohammed Zakiur; Hassan, Md Abul; Faiz, M A; Hossain, Moazzem; Hussain, Maleeha; Rashid, Mohammad Abdur

2009-12-01

The present study describes the ethnobotanical, phytochemical, and toxicological evaluations of Xanthium strumarium L. growing in Bangladesh. In toxicity evaluation on rats, the methanol extract of seedlings showed mortality, while both seedling and mature plant extracts raised the serum alanine transaminase and aspartate transaminase values and produced significant abnormalities in the histopathology of liver and kidney of rats. On the other hand, the aqueous soluble fraction of methanol extract of mature plant (LC50 = 0.352 microg/mL) and methanol crude extract of seedlings (LC50 = 0.656 microg/mL) demonstrated significant toxicity in the brine shrimp lethality bioassay. A total of four compounds were purified and characterized as stigmasterol (1), 11-hydroxy-11-carboxy-4-oxo-1(5),2(Z)-xanthadien-12,8-olide (2), daucosterol (3) and lasidiol-10-anisate (4). The present study suggests that X. strumarium is toxic to animal.

Vinyl Chloride: A Case Study of Data Suppression and Misrepresentation

PubMed Central

Sass, Jennifer Beth; Castleman, Barry; Wallinga, David

2005-01-01

When the U.S. Environmental Protection Agency (EPA) finalized its 2000 update of the toxicological effects of vinyl chloride (VC), it was concerned with two issues: the classification of VC as a carcinogen and the numerical estimate of its potency. In this commentary we describe how the U.S. EPA review of VC toxicology, which was drafted with substantial input from the chemical industry, weakened safeguards on both points. First, the assessment downplays risks from all cancer sites other than the liver. Second, the estimate of cancer potency was reduced 10-fold from values previously used for environmental decision making, a finding that reduces the cost and extent of pollution reduction and cleanup measures. We suggest that this assessment reflects discredited scientific practices and recommend that the U.S. EPA reverse its trend toward ever-increasing collaborations with the regulated industries when generating scientific reviews and risk assessments. PMID:16002366

Comparative toxicology of laboratory organisms for assessing hazardous-waste sites

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

Miller, W.E.; Peterson, S.A.; Greene, J.C.

1985-01-01

Multi-media/multi-trophic level bioassays have been proposed to determine the extent and severity of environmental contamination at hazardous waste sites. Comparative toxicological profiles for algae, daphnia, earthworms, microbes, mixed sewage and plants; wheat Stephens, lettuce, butter crunch, radish, Cherry Belle, red clover, Kenland, and cucumber, Spartan Valor are presented for selected heavy metals, herbicides and insecticides. Specific chemical EC50 values are presented for each test organism. Differences in standard deviations were compared between each individual test organism, as well as for the chemical subgroup assayed. Algae and daphnia are the most sensitive test organisms to heavy metals and insecticides followed inmore » order of decreasing sensitivity by Microtox, DO depletion rate, seed germination and earthworms. Differences in toxicity of 2,4-D chemical formulations and commercial sources of insecticides were observed with algae and daphnia tests.« less

Biological, medicinal and toxicological significance of Eucalyptus leaf essential oil: a review.

PubMed

Dhakad, Ashok K; Pandey, Vijay V; Beg, Sobia; Rawat, Janhvi M; Singh, Avtar

2018-02-01

The genus Eucalyptus L'Heritier comprises about 900 species, of which more than 300 species contain volatile essential oil in their leaves. About 20 species, within these, have a high content of 1,8-cineole (more than 70%), commercially used for the production of essential oils in the pharmaceutical and cosmetic industries. However, Eucalyptus is extensively planted for pulp, plywood and solid wood production, but its leaf aromatic oil has astounding widespread biological activities, including antimicrobial, antiseptic, antioxidant, chemotherapeutic, respiratory and gastrointestinal disorder treatment, wound healing, and insecticidal/insect repellent, herbicidal, acaricidal, nematicidal, and perfumes, soap making and grease remover. In the present review, we have made an attempt to congregate the biological ingredients of leaf essential oil, leaf oil as a natural medicine, and pharmacological and toxicological values of the leaf oil of different Eucalyptus species worldwide. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Risk assessment of manganese: A comparison of oral and inhalation derivations

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

Poirier, K.A.; Velazquez, S.F.

1991-03-11

An oral and inhalation human exposure-response risk assessment was calculated for manganese (Mn) using USEPA methodologies for both oral reference dose (RfD) and inhalation reference concentration (RfC) determination. When ingested, Mn is among the least toxic of the essential trace elements. The RfD for Mn is based on ingestion data from normal human diets, balance studies and neurotoxicity resulting from drinking contaminated well water. From these data, a NOAEL of 0.14 mg/kb/day was estimated. Since the NOAEL was thought to account for human sensitivity and Mn is an essential element required for normal human growth, an uncertainty factor (UF) ofmore » 1 was used resulting in a RfD of 1E-1 mg/kg/day. Although neurotoxic effects are rarely observed from oral exposures, they are more commonly associated with exposure to Mn by inhalation. Toxicity from inhaled Mn results in an increased prevalence of respiratory symptoms, reproductive dysfunction and psychomotor disturbances that can ultimately be expressed in a frank effect of manganism characterized by Parkinson disease-like symptoms. Using data from occupational exposure to in organic Mn, a dose duration adjusted LOAEL of 0.34 mg/m{sup 3} is identified. Application of an UF of 300 results in an RfC of 4E-4 mg/m{sup 3}. The RfD and RfC analyses demonstrate a dichotomous data set of toxicological effects dependent upon the route of exposure to Mn. Furthermore, these analyses demonstrate the unique issues of characterizing toxicological risk assessment for essential trace elements.« less

Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 476

NASA Technical Reports Server (NTRS)

1998-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Drug screening in clinical or forensic toxicology: are there differences?

PubMed

Gerostamoulos, Dimitri; Beyer, Jochen

2010-09-01

Legal and medical practitioners need to remember that, with respect to drug analysis, there are two distinct disciplines in analytical toxicology concerned with human biological matrices, namely clinical and forensic toxicology. Both fields use similar analytical techniques designed to detect and quantify drugs, chemicals and poisons in fluids or tissues. In clinical toxicology, analytical results help to specify the appropriate treatment of a poisoned or intoxicated patient. In forensic toxicology, the results often play a vital role in determining the possible impairment or behavioural changes in an individual, or the contribution of drugs or poisons to death in a medico-legal investigation. This column provides an overview of the similarities and differences inherent in clinical and forensic toxicology.

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)

Novel ion imprinted magnetic mesoporous silica for selective magnetic solid phase extraction of trace Cd followed by graphite furnace atomic absorption spectrometry detection

NASA Astrophysics Data System (ADS)

Zhao, Bingshan; He, Man; Chen, Beibei; Hu, Bin

2015-05-01

Determination of trace Cd in environmental, biological and food samples is of great significance to toxicological research and environmental pollution monitoring. While the direct determination of Cd in real-world samples is difficult due to its low concentration and the complex matrix. Herein, a novel Cd(II)-ion imprinted magnetic mesoporous silica (Cd(II)-II-MMS) was prepared and was employed as a selective magnetic solid-phase extraction (MSPE) material for extraction of trace Cd in real-world samples followed by graphite furnace atomic absorption spectrometry (GFAAS) detection. Under the optimized conditions, the detection limit of the proposed method was 6.1 ng L- 1 for Cd with the relative standard deviation (RSD) of 4.0% (c = 50 ng L- 1, n = 7), and the enrichment factor was 50-fold. To validate the proposed method, Certified Reference Materials of GSBZ 50009-88 environmental water, ZK018-1 lyophilized human urine and NIES10-b rice flour were analyzed and the determined values were in a good agreement with the certified values. The proposed method exhibited a robust anti-interference ability due to the good selectivity of Cd(II)-II-MMS toward Cd(II). It was successfully employed for the determination of trace Cd(II) in environmental water, human urine and rice samples with recoveries of 89.3-116%, demonstrating that the proposed method has good application potential in real world samples with complex matrix.

Using In Vitro High-Throughput Screening Data for Predicting ...

EPA Pesticide Factsheets

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values and risk screening values. We aim to use computational toxicology and quantitative high throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. By coupling qHTS data with adverse outcome pathways (AOPs) we can use ontologies to make predictions about potential hazards and to identify those assays which are sufficient to infer these same hazards. Once those assays are identified, we can use bootstrap natural spline-based metaregression to integrate the evidence across multiple replicates or assays (if a combination of assays are together necessary to be sufficient). In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene (B[k]F) may induce DNA damage and steatosis using qHTS data and two separate AOPs. We also demonstrate how bootstrap natural spline-based metaregression can be used to integrate the data across multiple assay replicates to generate a concentration-response curve. We used this analysis to calculate an internal point of departure of 0.751µM and risk-specific concentrations of 0.378µM for both 1:1,000 and 1:10,000 additive risk for B[k]F induced DNA damage based on the p53 assay. Based on the available evidence, we

Seasonal variation in diagnostic enzymes and biochemical constituents of captive northern bobwhites and passerines

USGS Publications Warehouse

Hill, E.F.; Murray, H.C.

1987-01-01

1. A variety of biochemical measurements were taken periodically in captive northern bobwhite (Colinus virginianus L.), European starlings (Sturnus vulgaris L.), red-winged blackbirds (Agelaius phoeniceus L.) and common grackles (Quiscalus quiscula L.) to determine whether baseline values remain sufficiently stable throughout the year for general clinical use in the absence of concurrent control specimens.2. Variables included whole blood hemotacrit and hemoglobin, plasma lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alinine aminotransferase, creatine kinase, butyrylcholinesterase, alkaline phosphatase, glucose, albumin, total protein, creatinine, urea nitrogen, uric acid, cholesterol, and triglycerides, and brain acetylcholinesterase. Butyrl- and acetylcholinesterase were included because of their specific uses in toxicology.3. Significant seasonal differences were detected for each of the variables except brain acetylcholinesterase in at least one of the species. Significant species differences were detected during at least one season for all of the variables measured.4. All species were maintained outdoors, but only northern bobwhites came into reproductive condition and showed sex-differences in the clinical variables during their normal breeding season.5. It was concluded that reference values for the 18 clinical variables measured could be calculated from our data for adult specimens of the species studied, and that results for one species cannot be extrapolated with certainty to any other species.6. Estimated normal bounds for each of the 18 variables measured by commonly used clinical procedures are presented for reproductively quiescent northern bobwhites, European starlings, red-winged blackbirds, and common grackles.

Translational toxicology: a developmental focus for integrated research strategies.

PubMed

Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo

2013-09-30

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? 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. 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.

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future.

PubMed

Orr, Michael S

2014-05-01

To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as 'e-cigarettes' and 'electronic delivery devices' were used to identify the toxicology information for e-cigarettes. As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users' toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes.

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future

PubMed Central

Orr, Michael S

2014-01-01

Objective To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Methods Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as ‘e-cigarettes’ and ‘electronic delivery devices’ were used to identify the toxicology information for e-cigarettes. Results As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Conclusions Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users’ toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes. PMID:24732158

Urine toxicology screening in an urban stroke and TIA population.

PubMed

Silver, Brian; Miller, Daniel; Jankowski, Michelle; Murshed, Nawaf; Garcia, Patricia; Penstone, Patricia; Straub, Melissa; Logan, Sean P; Sinha, Anita; Morris, Daniel C; Katramados, Angelos; Russman, Andrew N; Mitsias, Panayiotis D; Schultz, Lonni R

2013-04-30

We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department. In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients. A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (<50 years) and black race (<0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients. In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.

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.

Multifaceted toxicity assessment of catalyst composites in transgenic zebrafish embryos.

PubMed

Jang, Gun Hyuk; Lee, Keon Yong; Choi, Jaewon; Kim, Sang Hoon; Lee, Kwan Hyi

2016-09-01

Recent development in the field of nanomaterials has given rise into the inquiries regarding the toxicological characteristics of the nanomaterials. While many individual nanomaterials have been screened for their toxicological effects, composites that accompany nanomaterials are not common subjects to such screening through toxicological assessment. One of the widely used composites that accompany nanomaterials is catalyst composite used to reduce air pollution, which was selected as a target composite with nanomaterials for the multifaceted toxicological assessment. As existing studies did not possess any significant data regarding such catalyst composites, this study focuses on investigating toxicological characteristics of catalyst composites from various angles in both in-vitro and in-vivo settings. Initial toxicological assessment on catalyst composites was conducted using HUVECs for cell viability assays, and subsequent in-vivo assay regarding their direct influence on living organisms was done. The zebrafish embryo and its transgenic lines were used in the in-vivo assays to obtain multifaceted analytic results. Data obtained from the in-vivo assays include blood vessel formation, mutated heart morphology, and heart functionality change. Our multifaceted toxicological assessment pointed out that chemical composites augmented with nanomaterials can too have toxicological threat as much as individual nanomaterials do and alarms us with their danger. This manuscript provides a multifaceted assessment for composites augmented with nanomaterials, of which their toxicological threats have been overlooked. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicology Testing in Fatally Injured Workers: A Review of Five Years of Iowa FACE Cases

PubMed Central

Ramirez, Marizen; Bedford, Ronald; Sullivan, Ryan; Anthony, T. Renee; Kraemer, John; Faine, Brett; Peek-Asa, Corinne

2013-01-01

Toxicology testing of fatally injured workers is not routinely conducted. We completed a case-series study of 2005–2009 occupational fatalities captured by Iowa’s Fatality Assessment and Control Evaluation (FACE) Program. The goals of our research were to: (1) measure the proportion of FACE cases that undergo toxicology testing, and describe the factors associated with being tested, and (2) measure the rate of positive toxicology tests, the substances identified and the demographics and occupations of victims who tested positive. Case documents and toxicology laboratory reports were reviewed. There were 427 occupational deaths from 2005 to 2009. Only 69% underwent toxicology testing. Younger workers had greater odds of being tested. Among occupational groups, workers in farming, fishing and forestry had half the odds of being tested compared to other occupational groups. Of the 280 cases with toxicology tests completed, 22% (n = 61) were found to have positive toxicology testing. Commonly identified drug classes included cannabinoids and alcohols. Based on the small number of positive tests, older victims (65+ years) tested positive more frequently than younger workers. Management, business, science, arts, service and sales/office workers had proportionately more positive toxicology tests (almost 30%) compared with other workers (18–22%). These results identify an area in need of further research efforts and a potential target for injury prevention strategies. PMID:24240727

Analysis of Sertraline in Postmortem Fluids and Tissues in 11 Aviation Accident Victims

DTIC Science & Technology

2012-11-01

likely undergoes significant postmortem redistribution. 17. Key Words 18. Distribution Statement Forensic Toxicology , Sertraline, Norsertraline... Toxicology .. Forensic Sci Int,.142:.75-100.(2004) . 29 .. Skopp,.G ..Postmortem.Toxicology .. Forensic Sci Med Pathol,.6:.314-25.(2010) . ... toxicological . analysis. on. specimens.from.….aircraft.accident.fatalities”.and.“in- vestigate.….general.aviation.and.air.carrier.accidents. and. search

International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies*

PubMed Central

Bolon, Brad; Barale-Thomas, Erio; Bradley, Alys; Ettlin, Robert A.; Franchi, Carla A.S.; George, Catherine; Giusti, Anna Maria; Hall, Robert; Jacobsen, Matthew; Konishi, Yoichi; Ledieu, David; Morton, Daniel; Park, Jae-Hak; Scudamore, Cheryl L.; Tsuda, Hiroyuki; Vijayasarathi, S.K.; Wijnands, Marcel V.W.

2010-01-01

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job “apprenticeship,” at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one’s understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. PMID:22272030

A primer on systematic reviews in toxicology.

PubMed

Hoffmann, Sebastian; de Vries, Rob B M; Stephens, Martin L; Beck, Nancy B; Dirven, Hubert A A M; Fowle, John R; Goodman, Julie E; Hartung, Thomas; Kimber, Ian; Lalu, Manoj M; Thayer, Kristina; Whaley, Paul; Wikoff, Daniele; Tsaioun, Katya

2017-07-01

Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology community with a starting point for conducting or understanding systematic reviews, we herein summarized available guidance documents from various fields of application. We have elaborated on the systematic review process by breaking it down into ten steps, starting with planning the project, framing the question, and writing and publishing the protocol, and concluding with interpretation and reporting. In addition, we have identified the specific methodological challenges of toxicological questions and have summarized how these can be addressed. Ultimately, this primer is intended to stimulate scientific discussions of the identified issues to fuel the development of toxicology-specific methodology and to encourage the application of systematic review methodology to toxicological issues.

Forensic toxicology.

PubMed

Davis, Gregory G

2012-01-01

Toxicologic analysis is an integral part of death investigation, and the use or abuse of an unsuspected substance belongs in the differential diagnosis of patients who have a sudden, unexpected change in their condition. History and physical findings may alter suspicion that intoxication played a role in a patient's decline or death, but suspicions cannot be confirmed and is performed, analysis unless toxicologic no toxicologic analysis is possible unless someone collects the proper specimens necessary for analysis. In a hospital autopsy the only specimens that can rightfully be collected are those within the restrictions stated in the autopsy permit. Autopsies performed by the medical examiner do not have these restrictions. Sometimes the importance of toxicologic testing in a case is not evident until days or weeks after the change in the patient's status, thus retaining the appropriate specimens until investigation of that case has ended is important. Proper interpretation of toxicologic findings requires integrating the clinical setting and findings with the toxicologic results in a way that makes medical sense. If called upon to testify concerning findings, answer the questions truthfully, politely, and in a way that is understandable to someone who has no special training in toxicology.

Drug concentrations in post-mortem femoral blood compared with therapeutic concentrations in plasma

PubMed Central

Launiainen, Terhi; Ojanperä, Ilkka

2014-01-01

Therapeutic drug concentrations measured in plasma are of limited value as reference intervals for interpretation in post-mortem (PM) toxicology. In this study, drug concentration distributions were studied in PM femoral venous blood from 57 903 Finnish autopsy cases representing all causes of death during an 11-year period. Cause-of-death information was obtained from death certificates issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th, 97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median concentrations relate to established therapeutic ranges in plasma, a PM blood/plasma relationship was calculated for each drug. Males represented 75% of the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43% of these cases, blood alcohol concentration was higher than 0.2‰, and the median was 1.8‰. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs (35%), the relationship was >1. No marked correlation was found between the PM blood/plasma relationship and the volume of distribution (Vd). For 36 drugs, more than 10% of cases were fatal poisonings attributed to this drug as the main finding. These drug concentration distributions based on a large database provide a helpful reference not only to forensic toxicologists and pathologists but also to clinical pharmacologists in charge of interpreting drug concentrations in PM cases. © 2013 The Authors. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:23881890

A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

PubMed Central

Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

2015-01-01

Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

Advantages and Challenges of Dried Blood Spot Analysis by Mass Spectrometry Across the Total Testing Process.

PubMed

Zakaria, Rosita; Allen, Katrina J; Koplin, Jennifer J; Roche, Peter; Greaves, Ronda F

2016-12-01

Through the introduction of advanced analytical techniques and improved throughput, the scope of dried blood spot testing utilising mass spectrometric methods, has broadly expanded. Clinicians and researchers have become very enthusiastic about the potential applications of dried blood spot based mass spectrometric applications. Analysts on the other hand face challenges of sensitivity, reproducibility and overall accuracy of dried blood spot quantification. In this review, we aim to bring together these two facets to discuss the advantages and current challenges of non-newborn screening applications of dried blood spot quantification by mass spectrometry. To address these aims we performed a key word search of the PubMed and MEDLINE online databases in conjunction with individual manual searches to gather information. Keywords for the initial search included; "blood spot" and "mass spectrometry"; while excluding "newborn"; and "neonate". In addition, databases were restricted to English language and human specific. There was no time period limit applied. As a result of these selection criteria, 194 references were identified for review. For presentation, this information is divided into: 1) clinical applications; and 2) analytical considerations across the total testing process; being pre-analytical, analytical and post-analytical considerations. DBS analysis using MS applications is now broadly applied, with drug monitoring for both therapeutic and toxicological analysis being the most extensively reported. Several parameters can affect the accuracy of DBS measurement and further bridge experiments are required to develop adjustment rules for comparability between dried blood spot measures and the equivalent serum/plasma values. Likewise, the establishment of independent reference intervals for dried blood spot sample matrix is required.

A compilation of safety impact information for extractables associated with materials used in pharmaceutical packaging, delivery, administration, and manufacturing systems.

PubMed

Jenke, Dennis; Carlson, Tage

2014-01-01

Demonstrating suitability for intended use is necessary to register packaging, delivery/administration, or manufacturing systems for pharmaceutical products. During their use, such systems may interact with the pharmaceutical product, potentially adding extraneous entities to those products. These extraneous entities, termed leachables, have the potential to affect the product's performance and/or safety. To establish the potential safety impact, drug products and their packaging, delivery, or manufacturing systems are tested for leachables or extractables, respectively. This generally involves testing a sample (either the extract or the drug product) by a means that produces a test method response and then correlating the test method response with the identity and concentration of the entity causing the response. Oftentimes, analytical tests produce responses that cannot readily establish the associated entity's identity. Entities associated with un-interpretable responses are termed unknowns. Scientifically justifiable thresholds are used to establish those individual unknowns that represent an acceptable patient safety risk and thus which do not require further identification and, conversely, those unknowns whose potential safety impact require that they be identified. Such thresholds are typically based on the statistical analysis of datasets containing toxicological information for more or less relevant compounds. This article documents toxicological information for over 540 extractables identified in laboratory testing of polymeric materials used in pharmaceutical applications. Relevant toxicological endpoints, such as NOELs (no observed effects), NOAELs (no adverse effects), TDLOs (lowest published toxic dose), and others were collated for these extractables or their structurally similar surrogates and were systematically assessed to produce a risk index, which represents a daily intake value for life-long intravenous administration. This systematic approach uses four uncertainty factors, each assigned a factor of 10, which consider the quality and relevance of the data, differences in route of administration, non-human species to human extrapolations, and inter-individual variation among humans. In addition to the risk index values, all extractables and most of their surrogates were classified for structural safety alerts using Cramer rules and for mutagenicity alerts using an in silico approach (Benigni/Bossa rule base for mutagenicity via Toxtree). Lastly, in vitro mutagenicity data (Ames Salmonella typimurium and Mouse Lymphoma tests) were collected from available databases (Chemical Carcinogenesis Research Information and Carcinogenic Potency Database). The frequency distributions of the resulting data were established; in general risk index values were normally distributed around a band ranging from 5 to 20 mg/day. The risk index associated with 95% level of the cumulative distribution plot was approximately 0.1 mg/day. Thirteen extractables in the dataset had individual risk index values less than 0.1 mg/day, although four of these had additional risk indices, based on multiple different toxicological endpoints, above 0.1 mg/day. Additionally, approximately 50% of the extractables were classified in Cramer Class 1 (low risk of toxicity) and approximately 35% were in Cramer Class 3 (no basis to assume safety). Lastly, roughly 20% of the extractables triggered either an in vitro or in silico alert for mutagenicity. When Cramer classifications and the mutagenicity alerts were compared to the risk indices, extractables with safety alerts generally had lower risk index values, although the differences in the risk index data distributions, extractables with or without alerts, were small and subtle. Leachables from packaging systems, manufacturing systems, or delivery devices can accumulate in drug products and potentially affect the drug product. Although drug products can be analyzed for leachables (and material extracts can be analyzed for extractables), not all leachables or extractables can be fully identified. Safety thresholds can be used to establish whether the unidentified substances can be deemed to be safe or whether additional analytical efforts need to be made to secure the identities. These thresholds are typically based on the statistical analysis of datasets containing toxicological information for more or less relevant compounds. This article contains safety data for over 500 extractables that were identified in laboratory characterizations of polymers used in pharmaceutical applications. The safety data consists of structural toxicity classifications of the extractables as well as calculated risk indices, where the risk indices were obtained by subjecting toxicological safety data, such as NOELs (no observed effects), NOAELs (no adverse effects), TDLOs (lowest published toxic dose), and others to a systematic evaluation process using appropriate uncertainty factors. Thus the risk index values represent daily exposures for the lifetime intravenous administration of drugs. The frequency distributions of the risk indices and Cramer classifications were examined. The risk index values were normally distributed around a range of 5 to 20 mg/day, and the risk index associated with the 95% level of the cumulative frequency plot was 0.1 mg/day. Approximately 50% of the extractables were in Cramer Class 1 (low risk of toxicity) and approximately 35% were in Cramer Class 3 (high risk of toxicity). Approximately 20% of the extractables produced an in vitro or in silico mutagenicity alert. In general, the distribution of risk index values was not strongly correlated with the either extractables' Cramer classification or by mutagenicity alerts. However, extractables with either in vitro or in silico alerts were somewhat more likely to have low risk index values. © PDA, Inc. 2014.

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

42 CFR 493.937 - Toxicology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a laboratory's responses for quantitative toxicology tests or analytes, the program must compare the... sample in toxicology is the score determined under paragraph (c)(2) of this section. (2) For quantitative...

National toxicology program review of current DHHS, DOE, and EPA research related to toxicology, fiscal year 1996

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

NONE

1996-11-01

The Annual Plan for the National Toxicology Program requires an annual review of toxicology-related research supported by DHHS agencies. Four of the five Public Health Service Agencies support research related to toxicology. Within the National Institutes of Health alone, sixteen separate institutes and several other components support relevant research. Toxicology-related research is also conducted by other Federal agencies--particularly the Department of Energy (DOE) and the Environmental Protection Agency (EPA). An overall review is thought to be of considerable interest to research managers for purposes of coordinating research and reducing unnecessary duplication. This is the seventeenth review responding to this requirement.more » For the fifteenth time a survey of similar research at DOE and the EPA is included.« less

Stakeholder value-linked sustainability assessment: Evaluating remedial alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA.

PubMed

Apitz, Sabine E; Fitzpatrick, Anne G; McNally, Amanda; Harrison, David; Coughlin, Conor; Edwards, Deborah A

2018-01-01

Regulatory decisions on remediation should consider affected communities' needs and values, and how these might be impacted by remedial options; this process requires that diverse stakeholders are able to engage in a transparent consideration of value trade-offs and of the distribution of risks and benefits associated with remedial actions and outcomes. The Stakeholder Values Assessment (SVA) tool was developed to evaluate remedial impacts on environmental quality, economic viability, and social equity in the context of stakeholder values and priorities. Stakeholder values were linked to the pillars of sustainability and also to a range of metrics to evaluate how sediment remediation affects these values. Sediment remedial alternatives proposed by the US Environmental Protection Agency (USEPA) for the Portland Harbor Superfund Site were scored for each metric, based upon data provided in published feasibility study (FS) documents. Metric scores were aggregated to generate scores for each value; these were then aggregated to generate scores for each pillar of sustainability. In parallel, the inferred priorities (in terms of regional remediation, restoration, planning, and development) of diverse stakeholder groups (SGs) were used to evaluate the sensitivity and robustness of the values-based sustainability assessment to diverse SG priorities. This approach, which addresses social indicators of impact and then integrates them with indicators of environmental and economic impacts, goes well beyond the Comprehensive Environmental Response, Compensation and Liability Act's (CERCLA) 9 criteria for evaluating remedial alternatives because it evaluates how remedial alternatives might be ranked in terms of the diverse values and priorities of stakeholders. This approach identified trade-offs and points of potential contention, providing a systematic, semiquantitative, transparent valuation tool that can be used in community engagement. Integr Environ Assess Manag 2018;14:43-62. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Handbook of ecotoxicology, second edition

USGS Publications Warehouse

Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

2003-01-01

Handbook of Ecotoxicology, Second Edition focuses on toxic substances and how they affect ecosystems worldwide. It presents methods for quantifying and measuring ecotoxicological effects in the field and in the lab, as well as methods for estimating, predicting, and modeling in ecotoxicology studies. Completely revised and updated with 18 new chapters, this second edition includes contributions from over 75 international experts. Also, a Technical Review Board reviewed all manuscripts for accuracy and currency. This authoritative work is the definitive reference for students, researchers, consultants, and other professionals in the environmental sciences, toxicology, chemistry, biology, and ecology - in academia, industry, and government.

Respiratory Toxicology: 1981

DTIC Science & Technology

1981-08-01

AFAMRL-TR-81-81 D /a , 𔄁 RESPIRATORY TOXICOLOGY Annual Technical Report: 1981 P. E. NEWTON, Ph.D. UNIVERSITY OF CALIFORNIA, IRVINE OVERLOOK BRANCH...OF REPORT & PERIOD COVERED RESPIRATORY TOXICOLOGY: 1981 Annual Technical June 1980 through May 198 Ś. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(s) 8...ABSTRACT (Continue on reverse side if necessary and Identify by block number) The Respiratory Toxicology research programs conducted at the Toxic Hazards

75 FR 51815 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... water, consumption of contaminated food, ingestion of lead dust, eating of paint flakes by children..., renal toxicology, immunotoxicology, epidemiology, general toxicology, medicine, pharmacokinetics...

TOXLINE (TOXICOLOGY INFORMATION ONLINE)

EPA Science Inventory

TOXLINE? (TOXicology information onLINE) are the National Library of Medicines extensive collection of online bibliographic information covering the pharmacological, biochemical, physiological, and toxicological effects of drugs and other chemicals. TOXLINE and TOXLINE65 together...

An audit of the toxicology findings in 555 medico-legal autopsies finds manner of death changed in 5 cases.

PubMed

Langlois, Neil E I; Gilbert, John D; Heath, Karen J; Winskog, Calle; Kostakis, Chris

2013-03-01

An audit of toxicological analysis in Coronial autopsies performed at Forensic Science South Australia was conducted on the cases of three pathologists. Toxicological analysis had been performed in 555 (68 %) from a total of 815 autopsies. It was found that the proffered manner of death was changed from the provisional report (provided immediately after the post-mortem examination) in five cases (just under 1 %) as a consequence of the toxicological findings. This is a limited study as it is retrospective, not all cases had toxicological analysis and the findings are constrained by the range of the substances that could be detected. Nonetheless, the audit supports the application of toxicological analysis in medico-legal death investigation and suggests that an inclusive policy should be adopted.

Poisonings and clinical toxicology: a template for Ireland.

PubMed

Tormey, W P; Moore, T

2013-03-01

Poisons information is accessed around the clock in the British Isles from six centres of which two are in Ireland at Dublin and Belfast accompanied by consultant toxicologist advisory service. The numbers of calls in Ireland are down to about 40 per day due to easy access to online data bases. Access to Toxbase, the clinical toxicology database of the National Poisons Information Service is available to National Health Service (NHS) health professionals and to Emergency Departments and Intensive Care units in the Republic of Ireland. There are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates in Emergency Departments. All United States Poison Control Centres primarily use Poisindex which is a commercial database from Thomson Reuters. Information on paracetamol, diazepam, analgesics and psycho-active compounds are the commonest queries. Data from telephone and computer accesses provide an indicator of future trends in both licit and illicit drug poisons which may direct laboratory analytical service developments. Data from National Drug-Related Deaths Index is the most accurate information on toxicological deaths in Ireland. Laboratory toxicology requirements to support emergency departments are listed. Recommendations are made for a web-based open access Toxbase or equivalent; for a co-location of poisons information and laboratory clinical toxicology; for the establishment of a National Clinical Toxicology Institute for Ireland; for a list of accredited medical advisors in clinical toxicology; for multidisciplinary case conferences in complex toxicology cases for coroners; for the establishment of a national clinical toxicology referral out-patients service in Ireland.

Teens, Drugs, & Vegas: Toxicological surveillance of illicit prescription and illegal drug abuse in adolescents (12-17 years) using post-mortem data in Clark County, Nevada from 2005 to 2015.

PubMed

Paul, Anthea B Mahesan; Simms, Lary; Mahesan, Andrew A; Belanger, Eric Charles

2018-04-14

Illegal drug abuse, particularly prescription drug abuse is a growing problem in the United States. Research on adolescent drug abuse is based on national self-reported data. Using local coroner data, quantitative prevalence of illegal substance toxicology and trends can be assessed to aid directed outreach and community-based prevention initiatives. Retrospective analysis was conducted on all cases aged 12-17 years referred to the Office of the Medical Examiner, Clark County from 2005 to 2015 (n = 526). The prevalence of illegal opioid use in this population was 13.3%. The most commonly used drug was tetrahydrocannabinol (THC) in 29.7%. Illegal-prescription opioids and benzodiazepines were used approximately 1.7 times as much as all other illegal-drugs, excluding THC combined. The largest proportion of illicit prescription drug users were accidental death victims (p = 0.02, OR = 2.02). Drug trends by youth are ever evolving and current specific data is necessary to target prevention initiatives in local communities. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

The reduced-risk insecticide azadirachtin poses a toxicological hazard to stingless bee Partamona helleri (Friese, 1900) queens.

PubMed

Bernardes, Rodrigo Cupertino; Barbosa, Wagner Faria; Martins, Gustavo Ferreira; Lima, Maria Augusta Pereira

2018-06-01

Large-scale pesticide application poses a major threat to bee biodiversity by causing a decline in bee populations that, in turn, compromises ecosystem maintenance and agricultural productivity. Biopesticides are considered an alternative to synthetic pesticides with a focus on reducing potential detrimental effects to beneficial organisms such as bees. The production of healthy queen stingless bees is essential for the survival and reproduction of hives, although it remains unknown whether biopesticides influence stingless bee reproduction. In the present study, we investigated the effects of the biopesticide azadirachtin on the survival, behavior, morphology, development, and reproduction of queens of the stingless bee Partamona helleri (Friese, 1900). The neonicotinoid imidacloprid was used as a toxic reference standard. Queens were orally exposed in vitro to a contaminated diet (containing azadirachtin and imidacloprid) during development. Azadirachtin resulted in reduced survival, similarly to imidacloprid, altered development time, caused deformations, and reduced the size of the queens' reproductive organs. All of these factors could potentially compromise colony survival. Results from the present study showed azadirachtin posed a toxicological hazard to P. helleri queens. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analytical Strategies to Disclose Repeated Consumption of New Psychoactive Substances by Hair Analysis.

PubMed

Rotolo, Maria C; Klein, Julia; Pacifici, Roberta; Busardo, Francesco Paolo; Pichini, Simona; Marchei, Emilia

2017-01-01

New psychoactive substances (NPS) are a heterogenic group of substances with different chemical structures and psychotropic effects. Many pharmacotoxicological laboratories performing drug testing in conventional and nonconventional biological matrices for clinical and forensic purposes do not include screening procedures for NPS in their routine protocols. This is mainly due to the continued entry in the market of newly synthesized products, the low availability of reference standards, in particular of their metabolites, the low availability of immunochemical kits, etc. Moreover, many of the new compounds are very potent, and low doses ingested will lead to low concentrations in biological matrices, especially in hair. Hair analysis has become a powerful tool for detecting chronic drug use and has become a routine technique in forensic toxicology laboratories. The aim of this study was to set up analytical strategies to identify repeated consumption of NPS by hair analysis. Although UHPLC-MS/MS may represent the elective technique in studying NPS, a combination of both GC-MS and UHPLC-MS/MS techniques is useful in creating a complete toxicological image. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.

PubMed

Frazzoli, Chiara; Dragone, Roberto; Mantovani, Alberto; Massimi, Cristiana; Campanella, Luigi

2007-12-01

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.

Toxicological evaluation of hydrochlorofluorocarbon 142b.

PubMed

Seckar, J A; Trochimowicz, H J; Hogan, G K

1986-03-01

Groups of 110 rats of each sex were exposed by whole-body inhalation to 0, 1000, 10,000 or 20,000 ppm (v/v) of hydrochlorofluorocarbon 142b (CFC 142b or 1-chloro-1, 1-difluoroethane) for 6 hr/day, 5 days/wk for 104 wk (ten rats from each group were killed after 52 wk) in a combined chronic toxicity and oncogenicity study. Concurrently, ten male rats per group were exposed to the same concentrations for 13 wk in a bone-marrow cytogenicity study and another ten male rats per group were exposed for 15 wk in a dominant lethal study. No toxicologically significant compound-related effects were observed in behaviour, appearance, growth, clinical pathology, or gross and microscopic pathology. Respiratory infection and consequently higher than expected mortality during the first year did not compromise the studies or conclusions but may have contributed to the intergroup differences in the numbers of chromosome breaks and acentric fragments. No evidence for mutagenic potential was seen in either the dominant lethal or the cytogenetic assays. These data indicate the very low toxicity of CFC 142b with respect to chronic effects and genotoxic and oncogenic potential. The toxicological profile of CFC 142b is similar to that of other chlorofluorocarbons that have been assigned a threshold limit value (TLV) of 1000 ppm as a workplace 8-hr time-weighted average by the American Conference of Governmental Industrial Hygienists.

Mixture risk assessment: a case study of Monsanto experiences.

PubMed

Nair, R S; Dudek, B R; Grothe, D R; Johannsen, F R; Lamb, I C; Martens, M A; Sherman, J H; Stevens, M W

1996-01-01

Monsanto employs several pragmatic approaches for evaluating the toxicity of mixtures. These approaches are similar to those recommended by many national and international agencies. When conducting hazard and risk assessments, priority is always given to using data collected directly on the mixture of concern. To provide an example of the first tier of evaluation, actual data on acute respiratory irritation studies on mixtures were evaluated to determine whether the principle of additivity was applicable to the mixture evaluated. If actual data on the mixture are unavailable, extrapolation across similar mixtures is considered. Because many formulations are quite similar in composition, the toxicity data from one mixture can be extended to a closely related mixture in a scientifically justifiable manner. An example of a family of products where such extrapolations have been made is presented to exemplify this second approach. Lastly, if data on similar mixtures are unavailable, data on component fractions are used to predict the toxicity of the mixture. In this third approach, process knowledge and scientific judgement are used to determine how the known toxicological properties of the individual fractions affect toxicity of the mixture. Three examples of plant effluents where toxicological data on fractions were used to predict the toxicity of the mixture are discussed. The results of the analysis are used to discuss the predictive value of each of the above mentioned toxicological approaches for evaluating chemical mixtures.

An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

PubMed

Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

2011-06-01

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

[Threshold values for chemical agents in the light of the REACH regulation].

PubMed

Cavallo, Domenico Maria; Cattaneo, Andrea; Colosio, Claudio; Moretto, Angelo; Carrer, Paolo; Bartolucci, Giovanni Battista

2011-01-01

The European Regulation 1907/2006 (REACH--Registration, Evaluation, Authorization and Restriction of Chemicals) obliges manufacture companies and import chemicals to assess the risks arising from their use and to take the necessary measures to manage the risks identified. The Chemical Safety Report provides an accurate assessment of hazards to human health and the environment necessary to prepare an exposure scenario for the "identified uses" of the substance. An exposure scenario is the set of conditions that describe how the substance is manufactured or used during its life cycle and how the manufacturer or importer controls, or recommends downstream users to control the 'exposure to humans and the environment. Firms therefore need specific skills. The spectrum of toxicological risk is extremely large, the information required in some cases are very complex and undoubtedly require a thorough knowledge in toxicology and environmental industry. The expertise and experience in toxicology of the occupational physician in this case may become useful in the environmental field as well as another familiar figure of relevant importance is the occupational hygienist who develop exposure scenarios for workers and their uses experience for the exposure scenarios for the consumer. It provides an obvious involvement of medical toxicologists and occupational hygienists for public tasks of control and inspection of chemical safety reports and, locally, even the accuracy of risk that arise from this.

Comparison between self-report of cannabis use and toxicological detection of THC/THCCOOH in blood and THC in oral fluid in drivers in a roadside survey.

PubMed

Van der Linden, Trudy; Silverans, Peter; Verstraete, Alain G

2014-01-01

The objective of this study was to compare the number of drivers who self-reported cannabis use by questionnaires to the results of toxicological analysis. During roadside surveys, 2957 respondents driving a personal car or van completed a questionnaire to report their use of drugs and medicines during the previous two weeks and to indicate the time of their last intake. Cannabis was analyzed in oral fluid by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), in blood by gas chromatography-mass spectrometry (GC-MS). Frequencies in the time categories were calculated and compared with toxicological results. Diagnostic values were calculated for the time categories in which positive findings were to be expected (<4 h and <2 4h, respectively for tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinol (THCCOOH) in blood, <12 h for THC in oral fluid). Most self-reported cannabis use was more than 12 h before driving. The sensitivity of the questionnaire was low, while the specificity and accuracy were high. Kappa statistics revealed a fair agreement between self-report and positive findings for THC in oral fluid and blood and moderate agreement with THCCOOH in blood. Self-report largely underestimates driving under the influence of cannabis, particularly recent cannabis use; therefore analysis of biological samples is necessary. Copyright © 2013 John Wiley & Sons, Ltd.

[Forensic medicine as the cradle of toxicology in Russia].

PubMed

Popov, V L; Grebeniuk, A N; Pigolkin, Iu I; Tolmachev, I A; Bozhchenko, A P; Timoshevskiĭ, A A

2013-01-01

Modern toxicology as a science and educational subject originated from forensic medicine in the middle of the XIXth century. In the beginning, selected toxicological problems were taught in the Emperor's Medical Surgical Academy (presently S.M. Kirov Military Medical Academy, Sankt-Peterburg) and at the Medical Faculty of the Moscow University (presently I.M. Sechenov First Moscow State Medical University, Moscow). The greatest contribution to the development of toxicology was made by such outstanding scientists as professors S.A. Gromov, P.P. Pelekhin, P.P. Zablotsky-Desyatovsky, E.V. Pelikan, Ya.A. Chistovich, G.I. Blosfel'd, I.M. Sorokin, D.P. Kosorotov, A.V. Grigoriev, V.V. Andreev, A.A. Glebovich, A.N. Grigoriev, B.I. Predtechensky, V.M. Rozhkov, S.S. Vail, M.N. Lubotsky, etc. The works of these researchers predetermined the further development of toxicology in this country, its main purpose being provision of medical aid in case of poisoning and diseases of chemical etiology. Another line of toxicological research became industrial and environmental toxicology having the purpose of hygienic rating and prevention of poisoning. Nevertheless, all aspects of the multifaceted science of toxicology are related to forensic medicine as the cradle in which it originated, evolved, and turned into a self-consistent science.

High Throughput Transcriptomics @ USEPA (Toxicology ...

EPA Pesticide Factsheets

The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

Integrating the Principles of Toxicology into a Chemistry Curriculum

EPA Science Inventory

Designing safer products, processes and materials requires a commitment to engaging a transdisciplinary, systems approach utilizing the principles of chemistry, toxicology, environmental sciences and other allied disciplines. Chemistry and toxicology are inherently complementary ...

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...

A 90-day OECD TG 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of the aerosol from the carbon heated tobacco product version 1.2 (CHTP1.2) compared with cigarette smoke. I. Inhalation exposure, clinical pathology and histopathology.

PubMed

Phillips, Blaine W; Schlage, Walter K; Titz, Bjoern; Kogel, Ulrike; Sciuscio, Davide; Martin, Florian; Leroy, Patrice; Vuillaume, Gregory; Krishnan, Subash; Lee, Tom; Veljkovic, Emilija; Elamin, Ashraf; Merg, Celine; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia; Vanscheeuwijck, Patrick

2018-06-01

Within the framework of a systems toxicology approach, the inhalation toxicity of aerosol from a novel tobacco-heating potentially modified risk tobacco product (MRTP), the carbon-heated tobacco product (CHTP) 1.2, was characterized and compared with that of mainstream smoke (CS) from the 3R4F reference cigarette in a 90-day nose-only rat inhalation study in general accordance with OECD TG 413. CHTP1.2 is a heat-not-burn product using a carbon heat source to produce an aerosol that contains nicotine and tobacco flavor. At equal or twice the nicotine concentration in the test atmospheres, inhalation of CHTP1.2 aerosol led to a significantly lower exposure to harmful constituents and induced less respiratory tract irritation, systemic, and pathological effects compared with CS. Nasal epithelial changes were less pronounced in the CHTP1.2- than in the CS-exposed groups and reverted in the nicotine concentration-matched group after a recovery period. Lung inflammation was minimal in the CHTP1.2-treated groups compared with the moderate extent seen in the 3R4F groups. Many other toxicological endpoints evaluated did not show CHTP1.2 aerosol exposure-related effects, and no effects not seen for 3R4F were observed. These observations were consistent with findings from previous studies in which rats were exposed to MRTP aerosols containing similar nicotine concentrations. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats.

PubMed

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-12-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

PubMed Central

Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

2015-01-01

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats. PMID:26877840

ALiEM Blog and Podcast Watch: Toxicology.

PubMed

Zaver, Fareen; Craddick, Michael; Sanford, Audrey; Sefa, Nana; Hughes, George; Lin, Michelle

2017-10-01

The WestJEM Blog and Podcast Watch presents high-quality open-access educational blogs and podcasts in emergency medicine based on the ongoing Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) and AIR-Professional (Pro) series. Both series critically appraise open-access educational blogs and podcasts in EM using an objective scoring instrument. This installment of the blog and podcast watch series curated and scored relevant posts in the specific topic of toxicology emergencies from the AIR-Pro Series. The AIR-Pro Series is a continuously building curriculum covering a new subject area every two months. For each area, eight EM chief residents identify 3-5 advanced clinical questions. Using FOAMsearch.net and FOAMSearcher to search blogs and podcasts, relevant posts are scored by eight reviewers from the AIR-Pro editorial board, which is comprised of EM faculty and chief residents at various institutions across North America. The scoring instrument contains five measurement outcomes based on seven-point Likert scales: recency, accuracy, educational utility, evidence based, and references. The AIR-Pro label is awarded to posts with a score of ≥28 (out of 35) points. An "honorable mention" label is awarded if board members collectively felt that the blogs were valuable and the scores were > 25. A total of 31 blog posts and podcasts were included. Key educational pearls from the six high-quality AIR-Pro posts and four honorable mentions are summarized. The WestJEM ALiEM Blog and Podcast Watch series is based on the AIR and AIR-Pro Series, which attempts to identify high-quality educational content on open-access blogs and podcasts. This series provides an expert-based, crowdsourced approach towards critically appraising educational social media content for EM clinicians. This installment focuses on toxicology emergencies.

ALiEM Blog and Podcast Watch: Toxicology

PubMed Central

Zaver, Fareen; Craddick, Michael; Sanford, Audrey; Sefa, Nana; Hughes, George; Lin, Michelle

2017-01-01

Introduction The WestJEM Blog and Podcast Watch presents high-quality open-access educational blogs and podcasts in emergency medicine based on the ongoing Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) and AIR-Professional (Pro) series. Both series critically appraise open-access educational blogs and podcasts in EM using an objective scoring instrument. This installment of the blog and podcast watch series curated and scored relevant posts in the specific topic of toxicology emergencies from the AIR-Pro Series. Methods The AIR-Pro Series is a continuously building curriculum covering a new subject area every two months. For each area, eight EM chief residents identify 3–5 advanced clinical questions. Using FOAMsearch.net and FOAMSearcher to search blogs and podcasts, relevant posts are scored by eight reviewers from the AIR-Pro editorial board, which is comprised of EM faculty and chief residents at various institutions across North America. The scoring instrument contains five measurement outcomes based on seven-point Likert scales: recency, accuracy, educational utility, evidence based, and references. The AIR-Pro label is awarded to posts with a score of ≥28 (out of 35) points. An “honorable mention” label is awarded if board members collectively felt that the blogs were valuable and the scores were > 25. Results A total of 31 blog posts and podcasts were included. Key educational pearls from the six high-quality AIR-Pro posts and four honorable mentions are summarized. Conclusion The WestJEM ALiEM Blog and Podcast Watch series is based on the AIR and AIR-Pro Series, which attempts to identify high-quality educational content on open-access blogs and podcasts. This series provides an expert-based, crowdsourced approach towards critically appraising educational social media content for EM clinicians. This installment focuses on toxicology emergencies. PMID:29085545

Progress in computational toxicology.

PubMed

Ekins, Sean

2014-01-01

Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed. A literature review was performed on computational models for hepatotoxicity (e.g. for drug-induced liver injury (DILI)), cardiotoxicity, renal toxicity and genotoxicity. In addition various publications have been highlighted that use machine learning methods. Several computational toxicology model datasets from past publications were used to compare Bayesian and Support Vector Machine (SVM) learning methods. The increasing amounts of data for defined toxicology endpoints have enabled machine learning models that have been increasingly used for predictions. It is shown that across many different models Bayesian and SVM perform similarly based on cross validation data. Considerable progress has been made in computational toxicology in a decade in both model development and availability of larger scale or 'big data' models. The future efforts in toxicology data generation will likely provide us with hundreds of thousands of compounds that are readily accessible for machine learning models. These models will cover relevant chemistry space for pharmaceutical, consumer product and environmental applications. Copyright © 2013 Elsevier Inc. All rights reserved.

A practice analysis of toxicology.

PubMed

Wood, Carol S; Weis, Christopher P; Caro, Carla M; Roe, Amy

2016-12-01

In 2015, the American Board of Toxicology (ABT), with collaboration from the Society of Toxicology (SOT), in consultation with Professional Examination Service, performed a practice analysis study of the knowledge required for general toxicology. The purpose of this study is to help assure that the examination and requirements for attainment of Diplomate status are relevant to modern toxicology and based upon an empirical foundation of knowledge. A profile of the domains and tasks used in toxicology practice was developed by subject-matter experts representing a broad range of experiences and perspectives. An on-line survey of toxicologists, including Diplomates of the ABT and SOT members, confirmed the delineation. Results of the study can be used to improve understanding of toxicology practice, to better serve all toxicologists, and to present the role of toxicologists to those outside the profession. Survey results may also be used by the ABT Board of Directors to develop test specifications for the certifying examination and will be useful for evaluating and updating the content of professional preparation, development, and continuing education programs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of microgravity or simulated launch on testicular function in rats

NASA Technical Reports Server (NTRS)

Amann, R. P.; Deaver, D. R.; Zirkin, B. R.; Grills, G. S.; Sapp, W. J.; Veeramachaneni, D. N. R.; Clemens, J. W.; Banerjee, S. D.; Folmer, J.; Gruppi, C. M.

1992-01-01

Reproductive toxicology and cellular and molecular biology approaches were used to evaluate testicular function in rats from Cosmos 2044. It is found that concentrations of testosterone in testicular tissue or peripheral blood plasma were reduced in flight rates to less than 20 percent of values for simulated-launch or vivarium controls. Spermatogenesis was essentially normal in flight rats, but production of testosterone was severely depressed.

Toxicological properties of thio- and alkylphenols causing flavor tainting in fish from the upper Wisconsin River

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

Heil, T.P.; Lindsay, R.C.

1989-08-01

EC50 Microtox (5 min, 25 degrees C) assay values for 2-isopropylphenol, 3-isopropylphenol, 4-isopropylphenol, 2,4-diisopropylphenol, 2,5-diisopropylphenol 2,6-diisopropylphenol, 3,5-diisopropylphenol, carvacrol, thymol, thiophenol, and thiocresol ranged from 2 x 10(-2) mM for thymol (least toxic) to 2 x 10(-4) mM for 2,4-diisopropylphenol and 4-isopropylphenol (most toxic).

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach.

PubMed

Lachenmeier, Dirk W; Rehm, Jürgen

2015-01-30

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the "high risk" category with MOE < 10, the rest of the compounds except THC fall into the "risk" category with MOE < 100. On a population scale, only alcohol would fall into the "high risk" category, and cigarette smoking would fall into the "risk" category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk).

Identifying and designing chemicals with minimal acute aquatic toxicity

PubMed Central

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

2015-01-01

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

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

2015-05-19

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

Comparative risk assessment of alcohol, tobacco, cannabis and other illicit drugs using the margin of exposure approach

PubMed Central

Lachenmeier, Dirk W.; Rehm, Jürgen

2015-01-01

A comparative risk assessment of drugs including alcohol and tobacco using the margin of exposure (MOE) approach was conducted. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Median lethal dose values from animal experiments were used to derive the benchmark dose. The human intake was calculated for individual scenarios and population-based scenarios. The MOE was calculated using probabilistic Monte Carlo simulations. The benchmark dose values ranged from 2 mg/kg bodyweight for heroin to 531 mg/kg bodyweight for alcohol (ethanol). For individual exposure the four substances alcohol, nicotine, cocaine and heroin fall into the “high risk” category with MOE < 10, the rest of the compounds except THC fall into the “risk” category with MOE < 100. On a population scale, only alcohol would fall into the “high risk” category, and cigarette smoking would fall into the “risk” category, while all other agents (opiates, cocaine, amphetamine-type stimulants, ecstasy, and benzodiazepines) had MOEs > 100, and cannabis had a MOE > 10,000. The toxicological MOE approach validates epidemiological and social science-based drug ranking approaches especially in regard to the positions of alcohol and tobacco (high risk) and cannabis (low risk). PMID:25634572

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 490

NASA Technical Reports Server (NTRS)

1999-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

INAA Application for Trace Element Determination in Biological Reference Material

NASA Astrophysics Data System (ADS)

Atmodjo, D. P. D.; Kurniawati, S.; Lestiani, D. D.; Adventini, N.

2017-06-01

Trace element determination in biological samples is often used in the study of health and toxicology. Determination change to its essentiality and toxicity of trace element require an accurate determination method, which implies that a good Quality Control (QC) procedure should be performed. In this study, QC for trace element determination in biological samples was applied by analyzing the Standard Reference Material (SRM) Bovine muscle 8414 NIST using Instrumental Neutron Activation Analysis (INAA). Three selected trace element such as Fe, Zn, and Se were determined. Accuracy of the elements showed as %recovery and precision as %coefficient of variance (%CV). The result showed that %recovery of Fe, Zn, and Se were in the range between 99.4-107%, 92.7-103%, and 91.9-112%, respectively, whereas %CV were 2.92, 3.70, and 5.37%, respectively. These results showed that INAA method is precise and accurate for trace element determination in biological matrices.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 498

NASA Technical Reports Server (NTRS)

2000-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 487

NASA Technical Reports Server (NTRS)

1999-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 482

NASA Technical Reports Server (NTRS)

1999-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 502

NASA Technical Reports Server (NTRS)

2000-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 143

NASA Technical Reports Server (NTRS)

1975-01-01

This supplement to Aerospace Medicine and Biology (NASA SP-7011) lists 251 reports, articles and other documents announced during June 1975 in Scientific and Technical Aerospace Reports (STAR) or in International Aerospace Abstracts (IAA). The first issue of the bibliography was published in July 1964; since that time, monthly supplements have been issued. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 489

NASA Technical Reports Server (NTRS)

1999-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 477

NASA Technical Reports Server (NTRS)

1998-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 478

NASA Technical Reports Server (NTRS)

1998-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 504

NASA Technical Reports Server (NTRS)

2000-01-01

This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes- subject and author are included after the abstract section.

The uncertainty of reference standards--a guide to understanding factors impacting uncertainty, uncertainty calculations, and vendor certifications.

PubMed

Gates, Kevin; Chang, Ning; Dilek, Isil; Jian, Huahua; Pogue, Sherri; Sreenivasan, Uma

2009-10-01

Certified solution standards are widely used in forensic toxicological, clinical/diagnostic, and environmental testing. Typically, these standards are purchased as ampouled solutions with a certified concentration. Vendors present concentration and uncertainty differently on their Certificates of Analysis. Understanding the factors that impact uncertainty and which factors have been considered in the vendor's assignment of uncertainty are critical to understanding the accuracy of the standard and the impact on testing results. Understanding these variables is also important for laboratories seeking to comply with ISO/IEC 17025 requirements and for those preparing reference solutions from neat materials at the bench. The impact of uncertainty associated with the neat material purity (including residual water, residual solvent, and inorganic content), mass measurement (weighing techniques), and solvent addition (solution density) on the overall uncertainty of the certified concentration is described along with uncertainty calculations.

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)

Computational toxicity in 21st century safety sciences (China talk - Fuzhou China)

EPA Science Inventory

presentation at the Joint Meeting of Analytical Toxicology and Computational Toxicology Committee (Chinese Society of Toxicology) International Workshop on Advanced Chemical Safety Assessment Technologies on 11 May 2016, Fuzhou University, Fuzhou China

Humidifier disinfectant-associated specific diseases should be called together as “humidifier disinfectant syndrome”

PubMed Central

Lee, Jong-Hyeon

2017-01-01

Humidifier disinfectant (HD) damage was terrible chemical damage caused by household goods that happened in only South Korea, but still very little is known in HD damage. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchioles and alveoli because it is a specific finding, compared with other diseases. To figure out whole effects from HDs, much epidemiologic and toxicologic research is underway. HDs were shown to give rise to typical toxicologic effects on various target organs, such as skin, conjunctiva, naval mucosa, bronchial mucosa, alveoli and so on, which shared common toxicological responses. On a specific target, specific toxicologic effects existed. Diverse diseases along exposure pathways can occur at the same time with a common toxicologic mechanism and cause of HDs, which can be called as HD syndrome. To gain stronger scientific evidence about it, further epidemiological and toxicological studies should be applied. PMID:29026061

Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

PubMed

Hoenerhoff, Mark J; Hartke, James

2015-01-01

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum.

PubMed

Rothe, H; Obringer, C; Manwaring, J; Avci, C; Wargniez, W; Eilstein, J; Hewitt, N; Cubberley, R; Duplan, H; Lange, D; Jacques-Jamin, C; Klaric, M; Schepky, A; Grégoire, S

2017-07-01

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics-relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration-depth profile using tape-stripping (measures K SC/v and D SC /H SC 2 , where H SC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of K SC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures K SC/v and D SC /H SC 2 , and is based on Fick's laws). K SC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two-fold higher, and all values were within 10-fold of each other. Only indirect determination of K SC/v by Protocol 2B was different from the direct measurement of K SC/v by Protocol 2A and Protocol 1 for 7-EC. The variability of K SC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. D SC /H SC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, K SC/v, and D SC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

The relevance of "non-relevant metabolites" from plant protection products (PPPs) for drinking water: the German view.

PubMed

Dieter, Hermann H

2010-03-01

"Non-relevant metabolites" are those degradation products of plant protection products (PPPs), which are devoid of the targeted toxicities of the PPP and devoid of genotoxicity. Most often, "non-relevant metabolites" have a high affinity to the aquatic environment, are very mobile within this environment, and, usually, are also persistent. Therefore, from the point of drinking water hygiene, they must be characterized as "relevant for drinking water" like many other hydrophilic/polar environmental contaminants of different origins. "Non-relevant metabolites" may therefore penetrate to water sources used for abstraction of drinking water and may thus ultimately be present in drinking water. The presence of "non-relevant metabolites" and similar trace compounds in the water cycle may endanger drinking water quality on a long-term scale. During oxidative drinking water treatment, "non-relevant metabolites" may also serve as the starting material for toxicologically relevant transformation products similar to processes observed by drinking water disinfection with chlorine. This hypothesis was recently confirmed by the detection of the formation of N-nitroso-dimethylamine from ozone and dimethylsulfamide, a "non-relevant metabolite" of the fungicide tolylfluanide. In order to keep drinking water preferably free of "non-relevant metabolites", the German drinking water advisory board of the Federal Ministry of Health supports limiting their penetration into raw and drinking water to the functionally (agriculturally) unavoidable extent. On this background, the German Federal Environment Agency (UBA) recently has recommended two health related indication values (HRIV) to assess "non-relevant metabolites" from the view of drinking water hygiene. Considering the sometimes incomplete toxicological data base for some "non-relevant metabolites", HRIV also have the role of health related precautionary values. Depending on the completeness and quality of the toxicological evaluation of a "non-relevant metabolite", its HRIV is either set as 1.0 microg/l (HRIV(a)) or as 3.0 microg/l (HRIV(b)) for lifelong exposure. In case a HRIV would be exceeded, UBA recommends to keep on a precautionary action value (PAV) of 10 microg/l for each "non-relevant metabolite". The HRIV(b) is similar to the maximal value derived by application of the TTC-concept for Cramer Class III (4.5 microg/l). The HRIV(a) and the PAV are similar to values in the EU-guidance document for assessing "non-relevant metabolites" in ground water, with the important difference that the drinking water PAV is not intended to be tolerated for permanent exposure. Drinking water containing "non-relevant metabolites" below the respective HRIVs can also be considered as being sufficiently protective against toxicologically relevant oxidative transformation products which may be formed from "non-relevant metabolites" during drinking water treatment with ozone. However, even drinking water where one or several "non-relevant metabolites" are detected above substance-specific HRIVs is suited for human consumption without health risks. Only in special cases (relatively high "non-relevant metabolite" - concentrations), it could be indicated to examine the finished water for transformation products after treatment with ozone if there are no further treatment steps to eliminate or degrade polar compounds. UBA's "non-relevant metabolite-Recommendation" from April 2008 was positively picked up in 2009 by four important stakeholders in the domain of drinking water management as part of a voluntary cooperation agreement. The aim of such cooperation is to limit the transport of "non-relevant metabolites" into the drinking water to the functionally (and agriculturally) unavoidable extent and insofar to meet special precautionary demands. (c) 2009 Elsevier Inc. All rights reserved.

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

PubMed

Bluhm, Kerstin; Seiler, Thomas-Benjamin; Anders, Nico; Klankermayer, Jürgen; Schaeffer, Andreas; Hollert, Henner

2016-10-01

The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC50: 83mg/L) compared to 2-MTHF (LC50: 2980mg/L), 2-MF (LC50: 405mg/L) and water accommodated fractions of the reference fuels including gasoline (LC50: 244mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. Copyright © 2016 Elsevier B.V. All rights reserved.

IRIS Toxicological Review of Naphthalene (1998 Final)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of Naphthalene: in support of the Integrated Risk Information System (IRIS). The updated Summary for Naphthalene and accompanying toxicological review have been added to the IRIS Database.

Methodology for Uncertainty Analysis of Dynamic Computational Toxicology Models

EPA Science Inventory

The task of quantifying the uncertainty in both parameter estimates and model predictions has become more important with the increased use of dynamic computational toxicology models by the EPA. Dynamic toxicological models include physiologically-based pharmacokinetic (PBPK) mode...

IRIS Toxicological Review of Phosgene (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of Phosgene: in support of the Integrated Risk Information System (IRIS). The updated Summary for Phosgene and accompanying toxicological review have been added to the IRIS Database.

Environmental toxicology: Interconnections between human health and ecological integrity

EPA Science Inventory

This presentation will discuss what has made a career in environmental toxicology rewarding, environmental and scientific challenges for the 21st century, paradigm shift in regulatory toxicology, adverse outcome framework, interconnections between human health and ecological inte...

IRIS Toxicological Review of Acrolein (2003 Final)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of Acrolein: in support of the Integrated Risk Information System (IRIS). The updated Summary for Acrolein and accompanying toxicological review have been added to the IRIS Database.

Applications of Proteomic Technologies to Toxicology

EPA Science Inventory

Proteomics is the large-scale study of gene expression at the protein level. This cutting edge technology has been extensively applied to toxicology research recently. The up-to-date development of proteomics has presented the toxicology community with an unprecedented opportunit...

Safety assessment of plant varieties using transcriptomics profiling and a one-class classifier.

PubMed

van Dijk, Jeroen P; de Mello, Carla Souza; Voorhuijzen, Marleen M; Hutten, Ronald C B; Arisi, Ana Carolina Maisonnave; Jansen, Jeroen J; Buydens, Lutgarde M C; van der Voet, Hilko; Kok, Esther J

2014-10-01

An important part of the current hazard identification of novel plant varieties is comparative targeted analysis of the novel and reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, e.g. omics profiling. Data analysis estimating the similarity of new varieties to a reference baseline class of known safe varieties would subsequently greatly facilitate hazard identification. Further biological and eventually toxicological analysis would then only be necessary for varieties that fall outside this reference class. For this purpose, a one-class classifier tool was explored to assess and classify transcriptome profiles of potato (Solanum tuberosum) varieties in a model study. Profiles of six different varieties, two locations of growth, two year of harvest and including biological and technical replication were used to build the model. Two scenarios were applied representing evaluation of a 'different' variety and a 'similar' variety. Within the model higher class distances resulted for the 'different' test set compared with the 'similar' test set. The present study may contribute to a more global hazard identification of novel plant varieties. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabonomics and toxicology.

PubMed

Zhao, Liang; Hartung, Thomas

2015-01-01

Being an emerging field of "omics" research, metabonomics has been increasingly used in toxicological studies mostly because this technology has the ability to provide more detailed information to elucidate mechanism of toxicity. As an interdisciplinary field of science, metabonomics combines analytical chemistry, bioinformatics, statistics, and biochemistry. When applied to toxicology, metabonomics also includes aspects of patho-biochemistry, systems biology, and molecular diagnostics. During a toxicological study, the metabolic changes over time and dose after chemical treatment can be monitored. Therefore, the most important use of this emerging technology is the identification of signatures of toxicity-patterns of metabolic changes predictive of a hazard manifestation. This chapter summarizes the current state of metabonomics technology and its applications in various areas of toxicological studies.

PBPK-Based Probabilistic Risk Assessment for Total Chlorotriazines in Drinking Water.

PubMed

Breckenridge, Charles B; Campbell, Jerry L; Clewell, Harvey J; Andersen, Melvin E; Valdez-Flores, Ciriaco; Sielken, Robert L

2016-04-01

The risk of human exposure to total chlorotriazines (TCT) in drinking water was evaluated using a physiologically based pharmacokinetic (PBPK) model. Daily TCT (atrazine, deethylatrazine, deisopropylatrazine, and diaminochlorotriazine) chemographs were constructed for 17 frequently monitored community water systems (CWSs) using linear interpolation and Krieg estimates between observed TCT values. Synthetic chemographs were created using a conservative bias factor of 3 to generate intervening peaks between measured values. Drinking water consumption records from 24-h diaries were used to calculate daily exposure. Plasma TCT concentrations were updated every 30 minutes using the PBPK model output for each simulated calendar year from 2006 to 2010. Margins of exposure (MOEs) were calculated (MOE = [Human Plasma TCTPOD] ÷ [Human Plasma TCTEXP]) based on the toxicological point of departure (POD) and the drinking water-derived exposure to TCT. MOEs were determined based on 1, 2, 3, 4, 7, 14, 28, or 90 days of rolling average exposures and plasma TCT Cmax, or the area under the curve (AUC). Distributions of MOE were determined and the 99.9th percentile was used for risk assessment. MOEs for all 17 CWSs were >1000 at the 99.9(th)percentile. The 99.9(th)percentile of the MOE distribution was 2.8-fold less when the 3-fold synthetic chemograph bias factor was used. MOEs were insensitive to interpolation method, the consumer's age, the water consumption database used and the duration of time over which the rolling average plasma TCT was calculated, for up to 90 days. MOEs were sensitive to factors that modified the toxicological, or hyphenated appropriately no-observed-effects level (NOEL), including rat strain, endpoint used, method of calculating the NOEL, and the pharmacokinetics of elimination, as well as the magnitude of exposure (CWS, calendar year, and use of bias factors). © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Kinetic determination of vitellogenin induction in the epidermis of cyprinid and perciform fishes: Evaluation of sensitive enzyme-linked immunosorbent assays.

PubMed

Allner, Bernhard; Hennies, Mark; Lerche, Cristiano F; Schmidt, Thomas; Schneider, Klaus; Willner, Marco; Stahlschmidt-Allner, Petra

2016-12-01

Induction of vitellogenin (VTG) in male and immature fish is a standardized endpoint in endocrine-disruption testing. To establish a nondestructive swab sampling method, VTG induction in the epidermis of Cypriniformes and Perciformes species was investigated. Both VTG and estrogen receptor genes are expressed in epidermal cells. Immunoaffinity and mass fingerprint analyses show induction of identical VTG peptides in liver and epidermis. Induction of VTG by estradiol (E2) and bisphenol A (BPA) in the epidermis was quantified with homolog enzyme-linked immunosorbent assays. Initial values in juveniles and males were below 1 ng VTG/mL extraction buffer. Exposure to E2 led to values between 200 ng/mL and 4600 ng/mL in cyprinids and between 10 ng/mL and 81 ng/mL in perciforms. Exposure to BPA increased VTG amounts to 250 ng/mL in fathead minnows, 1360 ng/mL in goldfish, 100 ng/mL in zebrafish, and 12 ng/mL in bluegills. Serum VTG contents demonstrated a similar dose-response pattern in the epidermis and the blood. These results show that VTG induction may be reliably assessed in the skin mucus of fishes, demonstrating the suitability of this biological sample for investigating estrogenic activity in compliance with Organisation for Economic Co-operation and Development standard protocols. This broadens the perspectives in toxicological screening and environmental monitoring, reducing the number of tested animals and minimizing harmful effects for animals, allowing for follow-up of individual induction profiles. Environ Toxicol Chem 2016;35:2916-2930. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Derivation of a no-significant-risk-level for tetrabromobisphenol A based on a threshold non-mutagenic cancer mode of action.

PubMed

Pecquet, Alison M; Martinez, Jeanelle M; Vincent, Melissa; Erraguntla, Neeraja; Dourson, Michael

2018-06-01

A no-significant-risk-level of 20 mg day -1 was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2-year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non-mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfD cancer ). Using the National Toxicology Program data, we utilized Benchmark dose software to derive a benchmark dose lower limit (BMDL 10 ) as the point of departure (POD) of 103 mg kg -1  day -1 . The POD was adjusted to a human equivalent dose of 25.6 mg kg -1  day -1 using allometric scaling. We applied a composite adjustment factor of 100 to the POD to derive an RfD cancer of 0.26 mg kg -1  day -1 . Based on a human body weight of 70 kg, the RfD cancer was adjusted to a no-significant-risk-level of 20 mg day -1 . This was compared to other available non-cancer and cancer risk values, and aligns well with our understanding of the underlying biology based on the toxicology data. Overall, the weight of evidence from animal studies indicates that TBBPA has low toxicity and suggests that high doses over long exposure durations are needed to induce uterine tumor formation. Future research needs include a thorough and detailed vetting of the proposed adverse outcome pathway, including further support for key events leading to uterine tumor formation and a quantitative weight of evidence analysis. Copyright © 2018 John Wiley & Sons, Ltd.

Reuse and recycle--considering the soil below constructions.

PubMed

Suer, Pascal; Wik, Ola; Erlandsson, Martin

2014-07-01

The European Construction Products Regulation provides a life cycle based framework for the environmental assessment of construction products. Harmonised European standards for the assessment of the release of dangerous substances and for declaration of environmental performance are in progress. Risk based limit values for the protection of soil and groundwater below construction works will still bet set nationally. In this paper we review the possibilities to expand the ongoing harmonisation to include risk assessment and life cycle assessment (LCA). Based on reviews of national European limit value models (LMVs) for assessment of release to soil and groundwater, two areas for harmonisation emerge: 1- The toxicological criteria. Toxicological endpoints to protect human health and environment are similar, and data from the same toxicological data sets are used to establish acceptance criteria. 2- The emission part of LMVs. We extracted six generic construction works for granular materials. These encompass the most common choices and span the different release scenarios applied. Harmonised emission models would also facilitate LCA and environmental product declaration (EPD). The immission or transport part of the LVMs is less promising for harmonisation. Locating the acceptance criteria point of compliance close to the construction works is advantageous from many aspects and would facilitate harmonisation of assessments. We have identified two different strategies to include recycling in the assessments: 1- Tiered procedure where assessment and declaration of performance are made for the intended primary use of the product only and renewed assessments are made whenever the construction works are demolished and the product is recovered. 2- Scenario based procedure where future recycling scenarios, into new products and construction works, are forecasted. In this case the initial assessment and declaration of environmental performance of a construction product is performed both for the intended primary use of the product and for the recycling scenarios. Copyright © 2014 Elsevier B.V. All rights reserved.

[Geographical distribution of the Serum creatinine reference values of healthy adults].

PubMed

Wei, De-Zhi; Ge, Miao; Wang, Cong-Xia; Lin, Qian-Yi; Li, Meng-Jiao; Li, Peng

2016-11-20

To explore the relationship between serum creatinine (Scr) reference values in healthy adults and geographic factors and provide evidence for establishing Scr reference values in different regions. We collected 29 697 Scr reference values from healthy adults measured by 347 medical facilities from 23 provinces, 4 municipalities and 5 autonomous regions. We chose 23 geographical factors and analyzed their correlation with Scr reference values to identify the factors correlated significantly with Scr reference values. According to the Principal component analysis and Ridge regression analysis, two predictive models were constructed and the optimal model was chosen after comparison of the two model's fitting degree of predicted results and measured results. The distribution map of Scr reference values was drawn using the Kriging interpolation method. Seven geographic factors, including latitude, annual sunshine duration, annual average temperature, annual average relative humidity, annual precipitation, annual temperature range and topsoil (silt) cation exchange capacity were found to correlate significantly with Scr reference values. The overall distribution of Scr reference values featured a pattern that the values were high in the south and low in the north, varying consistently with the latitude change. The data of the geographic factors in a given region allows the prediction of the Scr values in healthy adults. Analysis of these geographical factors can facilitate the determination of the reference values specific to a region to improve the accuracy for clinical diagnoses.

Protecting Astronaut Health at First Entry into Vehicles Visiting the international Space Station: Insights from Whole-Module Offgas Testing

NASA Technical Reports Server (NTRS)

Meyers, Valerie

2014-01-01

NASA has accumulated considerable experience in offgas testing of whole modules prior to their docking with the International Space Station (ISS). Since 1998, the Space Toxicology Office has performed offgas testing of the Lab module, both MPLM modules, US Airlock, Node 1, Node 2, Node 3, ATV1, HTV1, and three commercial vehicles. The goal of these tests is twofold: first, to protect the crew from adverse health effects of accumulated volatile pollutants when they first enter the module on orbit, and secondly, to determine the additional pollutant load that the ISS air revitalization systems must handle. In order to predict the amount of accumulated pollutants, the module is sealed for at least 1/5th the worst-case time interval that could occur between the last clean air purge and final hatch closure on the ground and the crew's first entry on orbit. This time can range from a few days to a few months. Typically, triplicate samples are taken at pre-planned times throughout the test. Samples are then analyzed by gas chromatography and mass spectrometry, and the rate of accumulation of pollutants is then extrapolated over time. The analytical values are indexed against 7-day spacecraft maximum allowable concentrations (SMACs) to provide a prediction of the total toxicity value (T-value) at the time of first entry. This T-value and the toxicological effects of specific pollutants that contribute most to the overall toxicity are then used to guide first entry operations. Finally, results are compared to first entry samples collected on orbit to determine the predictive ability of the ground-based offgas test.

Inhalation Toxicology. 11. The Effect of Elevated Temperature on Carbon Monoxide Toxicity

DTIC Science & Technology

1990-12-01

DOT/FAA/AM-90/16 Inhalation Toxicology : XI. The Effect of Elevated Temperature on Carbon Office of Aviation Medicine Washington, D.C. 20591 M onoxide...Accession No. 3. Recipient’s Catalog No. DOT/FAA/AM-90/16 4. Title and Subtitie S. Report Date INHALATION TOXICOLOGY : XI. THE EFFECT OF ELEVATED December...Statement Combustion toxicology , carbon monoxide, This document is available to the public heat, thermal effects, time-to- through the National Technical

Assessing the scientific research productivity of a leading toxicology journal: A case study of Human & Experimental Toxicology from 2003 to 2012.

PubMed

Zyoud, Sa'ed H; Al-Jabi, Samah W; Sweileh, Waleed M; Awang, Rahmat

2014-01-01

Bibliometric studies are increasingly being used for research assessments. Bibliometric indicators involve the application of statistical methods to scientific publications to obtain the bibliographics for each journal. The main objective of this study was to conduct a bibliometric evaluation of Human & Experimental Toxicology retrieved from the Scopus database. This study obtained data from Scopus published from 1 January 2003 till 31 December 2012. The keywords entered in Scopus to accomplish the objective of this study were 'Human', 'Experimental' and 'Toxicology' as 'Source Title'. Research productivity was evaluated based on a methodology developed and used in other bibliometric studies by analysing (a) total and trends in Human & Experimental Toxicology contributions in research between 2003 and 2012; (b) Human & Experimental Toxicology authorship patterns and productivity; (c) collaboration patterns; and (d) the citations received by the publications. There were 1229 research articles published in Human & Experimental Toxicology. Of the articles included, 947 (77.1%) were original articles and 104 (8.5%) were review articles. The Hirsch-index of the retrieved documents was 35. The largest number of publications in Human & Experimental Toxicology was from the United States (19.6%), followed by India (12.8%) and Turkey (10.9%). The total number of citations was 9119, with a median (interquartile range) of 3 (1-9) in 6797 documents. The highest median (interquartile range) number of citations was 8 (2.7-12.7) for France, followed by 7.5 (2-22.5) for Iran and 6 (3-13.5) for the United Kingdom. The country most often citing articles that were published in Human & Experimental Toxicology was the United States, which made citations in 1508 documents, followed by India with citations in 792 documents. The documents in Human & Experimental Toxicology focus principally on original data, with very few review articles. Review articles tend to have higher citation rates than original articles, and hence, the editors and authors of Human & Experimental Toxicology might usefully promote the submission of reviews in the future to improve the impact of the journal.

PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

EPA Science Inventory

Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

IRIS Toxicological Review of Decabromodiphenyl Ether (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Toxicological Review of Decabromodiphenyl Ether: in support of the Integrated Risk Information System (IRIS). The updated Summary for Decabromodiphenyl Ether and accompanying toxicological review have been added to the IRIS Da...