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.

Maternal and fetal toxicity in developmental toxicology bioassays: Weight changes and their biological significance

EPA Science Inventory

Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines call for the inclusion of a dose level(s) that induces “overt maternal toxicity.” The possibility that general maternal toxicit...

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

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. 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 TCP 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 values for noncancer effects of TCP (RfD and RfC) 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 toxicity of TCP. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for 1,2,3-trichloropropane. IRIS is an EPA database containing the Agency's consensus scientific positions on potential adverse human effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment process, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in

Potential Health Effects from Groundwater Pollution.

ERIC Educational Resources Information Center

Goyer, Robert A.

1985-01-01

Discusses the growing awareness of potential toxicological effects of synthetic organic chemicals contaminating groundwater. Problems concerning pesticides, chlorination, epidemiologic studies, cancer, nephrotoxicity, and considerations of risk are addressed. Additional research in this area is advocated. (DH)

IRIS Toxicological Review of Biphenyl (Interagency Science ...

EPA Pesticide Factsheets

On September 30, 2011, the draft Toxicological Review of Biphenyl 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 Biphenyl and the charge to external peer reviewers are posted on this site. EPA is undertaking a new health assessment for biphenyl for the Integrated Risk Information System (IRIS). The outcome of this project will be a Toxicological Review and IRIS and IRIS Summary of biohenyl that will be entered on the IRIS database. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information to evaluate potential public health risks associated with exposure assessment information to evaluate potential public health risks associated with environmental contaminants. The IRIS database is relied on for the development of risk ass

Safety and Toxicology of Cannabinoids.

PubMed

Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

2015-10-01

There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will then be compared with the current social and political climate to suggest future policy directions and general guidelines.

Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

PubMed Central

Adami, Hans-Olov; Berry, Sir Colin L.; Breckenridge, Charles B.; Smith, Lewis L.; Swenberg, James A.; Trichopoulos, Dimitrios; Weiss, Noel S.; Pastoor, Timothy P.

2011-01-01

Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step “Epid-Tox” process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality. PMID:21561883

IRIS Toxicological Review of Thallium and Compounds ...

EPA Pesticide Factsheets

Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

Differential effects of p,p'-DDE on testis and liver mitochondria: implications for reproductive toxicology.

PubMed

Mota, Paula C; Cordeiro, Marília; Pereira, Susana P; Oliveira, Paulo J; Moreno, António J; Ramalho-Santos, João

2011-01-01

The release of environmental contaminants can contribute to impaired male fertility. The bioenergetics of isolated liver mitochondria have been used as a toxicological indicator, an inexpensive first line model to screen possible effects of several substances. Here we report the effects of 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethylene (DDE) on the bioenergetical parameters of testicular mitochondria. A significant decrease in repolarization potential (after a phosphorylative cycle), state 3 respiration and uncoupled respiration, with a concomitant increase in lag phase was found, demonstrating a decrease in mitochondrial function. Importantly, there was also a clear increase in maximum potential in DDE-treated testis mitochondria, which was not mirrored by more commonly used liver mitochondria. Indeed, comparative studies showed that testis and liver mitochondria have strikingly different sensitivities and patterns of response to DDE, indicating that testis mitochondria should be used as a primary toxicological model for a proper evaluation of putative effects of environmental toxicants on the bioenergetics of spermatogenesis and male fertility. Copyright © 2010 Elsevier Inc. All rights reserved.

EFFECTS OF SELECTED ORGANIC DRINKING WATER CONTAMINANTS ON MALE REPRODUCTION

EPA Science Inventory

Because of the recent increase in exposure of individuals to potentially harmful chemicals, it has become increasingly important to test the potential of environmental chemicals to cause adverse reproductive effects. The Division of Toxicology within the Department of Pharmacolog...

IRIS Toxicological Review of Trimethylbenzenes (Final Report ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Trimethylbenzenes (TMBs). This assessment addresses the potential non-cancer and cancer human health effects from long-term exposure to TMBs. Now final, this assessment will be the first IRIS assessment for TMBs that may be used by EPA’s program and regional offices to inform decisions to protect human health. The IRIS Toxicological Review of Trimethylbenzenes was originally released for a 60-day public comment period on June 29, 2012. EPA revised the toxicological review in response to the public comments received and released the finalized TMB assessment.

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics

PubMed Central

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration. PMID:29333505

Toxicological Implications of Released Particulate Matter during Thermal Decomposition of Nano-Enabled Thermoplastics.

PubMed

Watson-Wright, Christa; Singh, Dilpreet; Demokritou, Philip

2017-01-01

Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration.

Evaluating the mutagenic potential of aerosol organic compounds using informatics-based screening

NASA Astrophysics Data System (ADS)

Decesari, Stefano; Kovarich, Simona; Pavan, Manuela; Bassan, Arianna; Ciacci, Andrea; Topping, David

2018-02-01

Whilst general policy objectives to reduce airborne particulate matter (PM) health effects are to reduce exposure to PM as a whole, emerging evidence suggests that more detailed metrics associating impacts with different aerosol components might be needed. Since it is impossible to conduct toxicological screening on all possible molecular species expected to occur in aerosol, in this study we perform a proof-of-concept evaluation on the information retrieved from in silico toxicological predictions, in which a subset (N = 104) of secondary organic aerosol (SOA) compounds were screened for their mutagenicity potential. An extensive database search showed that experimental data are available for 13 % of the compounds, while reliable predictions were obtained for 82 %. A multivariate statistical analysis of the compounds based on their physico-chemical, structural, and mechanistic properties showed that 80 % of the compounds predicted as mutagenic were grouped into six clusters, three of which (five-membered lactones from monoterpene oxidation, oxygenated multifunctional compounds from substituted benzene oxidation, and hydroperoxides from several precursors) represent new candidate groups of compounds for future toxicological screenings. These results demonstrate that coupling model-generated compositions to in silico toxicological screening might enable more comprehensive exploration of the mutagenic potential of specific SOA components.

Screening Health Risk Assessment Burn Pit Exposures, Balad Air Base, Iraq and Addendum Report

DTIC Science & Technology

2008-05-01

risk uses principles drawn from many scientific disciplines including chemistry , toxicology, physics, mathematics, and statistics. Because the data...uses principles drawn from many scientific disciplines, including chemistry , toxicology, physics, mathematics, and statistics. Because the data...natural chemicals in plants (called flavonoids ) also act on the Ah-receptor and could potentially block the effects of dioxins. One more reason to

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

PubMed

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

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.

Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach

DTIC Science & Technology

2007-12-01

Melting point • Ionization potential (2) QSAR approaches can also be used to estimate toxicological impact. Toxicity QSAR models can often... TOXICOLOGY STUDY NO. 87-XE-03N3-05 ASSESSING THE POTENTIAL ENVIRONMENTAL CONSEQUENCES OF A NEW ENERGETIC MATERIAL: A PHASED APPROACH...SEPTEMBER 2005 Published: December 2007 Approved for public release; distribution unlimited. Toxicology Study No. 87-XE-03N3-05

The effect on toxicology, biochemistry and immunology investigations by the use of targeted post-mortem computed tomography angiography.

PubMed

Rutty, G N; Smith, P; Visser, T; Barber, J; Amorosa, J; Morgan, B

2013-02-10

It is recognised in autopsy practice that investigations such as toxicology can be affected by post-mortem change. Post-mortem computed tomography angiography (PMCT-A) involves the injection of contrast agents. This could cause dilution of a biological fluid sample or cause the circulation of blood after death by mechanical pumping, and thus has the potential to affect laboratory investigations. We undertook a small sample study to consider whether targeted PMCT-A had any significant effect on subsequent samples taken for biochemical, toxicological or immunological investigations. Although the results of our study do illustrate differences between the pre and post PMCT-A results, these differences are considered not to be of diagnostic significance and not due to the direct effect of targeted PMCT-A. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

PubMed

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

IRIS Toxicological Review of Tert-Butyl Alcohol (Tert-Butanol) ...

EPA Pesticide Factsheets

On April 29, 2016, the Toxicological Review of tert-Butyl Alcohol (tert-Butanol) (Public Comment Draft) was released for public comment. The draft Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and the Executive Office of the President during Step 3 (Interagency Science Consultation) before public release. As part of the IRIS process, all written interagency comments on IRIS assessments will be made publicly available. Accordingly, interagency comments with EPA's response and the interagency science consultation drafts of the IRIS Toxicological Review of tert-Butanol and charge to external peer reviewers are posted on this site. EPA is undertaking a new health assessment for t-butyl alcohol (tert-butanol) for the Integrated Risk Information System (IRIS). The outcome of this project will be a Toxicological Review and IRIS and IRIS Summary of TBA that will be entered on the IRIS database. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information to evaluate potential public health risks associated with environmental contaminants. The IRIS database is relied on for the development of risk assessments, site-specific environmental decisions, and rule making.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

EPA Pesticide Factsheets

EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. 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 Beryllium will consist of an updated 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 values for noncancer effects of Beryllium (RfD and RfC) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency and Interagency review, and external scientific peer review. The final products will constitute the Agency's opinion on the toxicity of Beryllium. Beryllium is a light alkaline earth metal used in metal alloys and in high-performance products in the metallurgical, aerospace, and nuclear industries. According to the Superfund database, beryllium is found in over 300 NPL sites

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

PubMed

Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

2017-12-01

With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Reviews of the toxicity behavior of five potential engineered nanomaterials (ENMs) into the aquatic ecosystem.

PubMed

Jahan, Shanaz; Yusoff, Ismail Bin; Alias, Yatimah Binti; Bakar, Ahmad Farid Bin Abu

2017-01-01

Presently, engineered nanomaterials (ENMs) are used in a wide variety of commercial applications, resulting in an uncontrolled introduction into the aquatic environment. The purpose of this review is to summarize the pathways and factors that controlling the transport and toxicity of five extensively used ENMs. These toxicological pathways are of great importance and need to be addressed for sustainable implications of ENMs without environmental liabilities. Here we discuss five potentially utilized ENMs with their possible toxicological risk factors to aquatic plants, vertebrates model and microbes. Moreover, the key effect of ENMs surface transformations by significant reaction with environmental objects such as dissolved natural organic matter (DOM) and the effect of ENMs surface coating and surface charge will also be debated. The transformations of ENMs are subsequently facing a major ecological transition that is expected to create a substantial toxicological effect towards the ecosystem. These transformations largely involve chemical and physical processes, which depend on the properties of both ENMs and the receiving medium. In this review article, the critical issues that controlling the transport and toxicity of ENMs are reviewed by exploiting the latest reports and future directions and targets are keenly discussed to minimize the pessimistic effects of ENMs.

IRIS Toxicological Review of Benzo[a]pyrene (Final Report) ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene. This assessment addresses the potential cancer and noncancer human health effects from long-term exposure to benzo[a]pyrene. Now final, this assessment will update the toxicological information on benzo[a]pyrene posted in 1987. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

Nanoparticles: pharmacological and toxicological significance

PubMed Central

Medina, C; Santos-Martinez, M J; Radomski, A; Corrigan, O I; Radomski, M W

2007-01-01

Nanoparticles are tiny materials (<1000 nm in size) that have specific physicochemical properties different to bulk materials of the same composition and such properties make them very attractive for commercial and medical development. However, nanoparticles can act on living cells at the nanolevel resulting not only in biologically desirable, but also in undesirable effects. In contrast to many efforts aimed at exploiting desirable properties of nanoparticles for medicine, there are limited attempts to evaluate potentially undesirable effects of these particles when administered intentionally for medical purposes. Therefore, there is a pressing need for careful consideration of benefits and side effects of the use of nanoparticles in medicine. This review article aims at providing a balanced update of these exciting pharmacological and potentially toxicological developments. The classes of nanoparticles, the current status of nanoparticle use in pharmacology and therapeutics, the demonstrated and potential toxicity of nanoparticles will be discussed. PMID:17245366

Toxicological challenges to microbial bioethanol production and strategies for improved tolerance

DOE PAGES

Akinsho, Hannah; Rydzak, Thomas; Borole, Abhijeet P.; ...

2015-09-30

Bioethanol production output has increased steadily over the last two decades and is now beginning to become competitive with traditional liquid transportation fuels due to advances in engineering, the identification of new production host organisms, and the development of novel biodesign strategies. A significant portion of these efforts has been dedicated to mitigating the toxicological challenges encountered across the bioethanol production process. From the release of potentially cytotoxic or inhibitory compounds from input feedstocks, through the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and to the potential cytotoxicity of ethanol itself, each stage of bioethanol production requires the applicationmore » of genetic or engineering controls that ensure the host organisms remain healthy and productive to meet the necessary economies required for large scale production. In addition, as production levels continue to increase, there is an escalating focus on the detoxification of the resulting waste streams to minimize their environmental impact. Thus, this review will present the major toxicological challenges encountered throughout each stage of the bioethanol production process and the commonly employed strategies for reducing or eliminating potential toxic effects.« less

Anxiolytic-like effects and toxicological studies of Brickellia cavanillesii (Cass.) A. Gray in experimental mice models.

PubMed

Ávila-Villarreal, Gabriela; González-Trujano, María Eva; Carballo-Villalobos, Azucena Ibeth; Aguilar-Guadarrama, Berenice; García-Jiménez, Sara; Giles-Rivas, Diana Elizabeth; Castillo-España, Patricia; Villalobos-Molina, Rafael; Estrada-Soto, Samuel

2016-11-04

Brickellia cavanillesii (Asteraceae) (Cass.) A. Gray is one of the popular plants consumed in Central America and Mexico for the treatment of several diseases such as hypertension, diabetes and anxiety, among others. To determine the anxiolytic-like effect of B. Cavanillesii and the safety of its use through toxicological studies. Anxiolytic-like effects of soluble-methanol extract of B. cavanillesii (MEBc) were evaluated in ambulatory activity (open-field test), hole-board test, cylinder of exploration, the elevated plus-maze and the potentiation of the sodium pentobarbital-induced hypnosis mice models. On the other hand, in vivo toxicological studies were conducted on acute and sub-acute mice models recommended by OECD. Active MEBc was subjected to phytochemical studies through conventional chromatographic techniques to isolate bioactive compounds. MEBc (100mg/Kg) showed significant anxiolytic-like effect on animal model used (p<0.05). The phytochemical analysis of MEBc allowed the isolation of two major compounds nicotiflorin and acacetin, among others. Both compounds were found to be partially responsible for the anxiolytic-like effects. Moreover, a median lethal dose (LD 50 ) higher than 2000mg/Kg was determined in mice and sub-acute oral administration of MEBc (100mg/Kg) did not alter body weight, clinical chemistry parameters (ALT and AST) and it did not induce any toxic nor alteration in the liver, kidney and heart functions. In current investigation, we have shown that MEBc has a wide range of pharmacology-toxicology patterns. The results support further investigation of MEBc as a potential anxiolytic phytomedicinal agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Present state and future perspectives of using pluripotent stem cells in toxicology research

PubMed Central

Löser, Peter

2011-01-01

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed. PMID:21225242

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

In vitro toxicological characterization of particulate emissions from residential biomass heating systems based on old and new technologies

NASA Astrophysics Data System (ADS)

Jalava, Pasi I.; Happo, Mikko S.; Kelz, Joachim; Brunner, Thomas; Hakulinen, Pasi; Mäki-Paakkanen, Jorma; Hukkanen, Annika; Jokiniemi, Jorma; Obernberger, Ingwald; Hirvonen, Maija-Riitta

2012-04-01

Residential wood combustion causes major effects on the air quality on a global scale. The ambient particulate levels are known to be responsible for severe adverse health effects that include e.g. cardio-respiratory illnesses and cancer related effects, even mortality. It is known that biomass combustion derived emissions are affected by combustion technology, fuel being used and user-related practices. There are also indications that the health related toxicological effects are influenced by these parameters. This study we evaluated toxicological effects of particulate emissions (PM1) from seven different residential wood combusting furnaces. Two appliances i.e. log wood boiler and stove represented old batch combustion technology, whereas stove and tiled stove were designated as new batch combustion as three modern automated boilers were a log wood boiler, a woodchip boiler and a pellet boiler. The PM1 samples from the furnaces were collected in an experimental setup with a Dekati® gravimetric impactor on PTFE filters with the samples being weighed and extracted from the substrates and prior to toxicological analyses. The toxicological analyses were conducted after a 24-hour exposure of the mouse RAW 264.7 macrophage cell line to four doses of emission particle samples and analysis of levels of the proinflammatory cytokine TNFα, chemokine MIP-2, cytotoxicity with three different methods (MTT, PI, cell cycle analysis) and genotoxicity with the comet assay. In the correlation analysis all the toxicological results were compared with the chemical composition of the samples. All the samples induced dose-dependent increases in the studied parameters. Combustion technology greatly affected the emissions and the concomitant toxicological responses. The modern automated boilers were usually the least potent inducers of most of the parameters while emissions from the old technology log wood boiler were the most potent. In correlation analysis, the PAH and other organic composition and inorganic ash composition affected the toxicological responses differently. In conclusion, combustion technology largely affects the particulate emissions and their toxic potential this being reflected in substantially larger responses in devices with incomplete combustion. These differences become emphasized when the large emission factors from old technology appliances are taken into account.

Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century.

PubMed

Xia, Tian; Zhu, Yifang; Mu, Lina; Zhang, Zuo-Feng; Liu, Sijin

2016-12-01

Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM 2.5 ) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM 2.5 concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM 2.5 . In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future.

METABOLOMICS IN SMALL FISH TOXICOLOGY AND ECOLOGICAL RISK ASSESSMENTS

EPA Science Inventory

The US EPA is tasked with protecting not only humans, but also ecosystems from potentially harmful effects of chemical pollutants. Although lagging behind applications targeted to human endpoints, metabolomics offers great potential in ecotoxicology. Indeed, the advantages of met...

Nano-technology and nano-toxicology.

PubMed

Maynard, Robert L

2012-01-01

Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology.

Nano-technology and nano-toxicology

PubMed Central

Maynard, Robert L.

2012-01-01

Rapid developments in nano-technology are likely to confer significant benefits on mankind. But, as with perhaps all new technologies, these benefits are likely to be accompanied by risks, perhaps by new risks. Nano-toxicology is developing in parallel with nano-technology and seeks to define the hazards and risks associated with nano-materials: only when risks have been identified they can be controlled. This article discusses the reasons for concern about the potential effects on health of exposure to nano-materials and relates these to the evidence of the effects on health of the ambient aerosol. A number of hypotheses are proposed and the dangers of adopting unsubstantiated hypotheses are stressed. Nano-toxicology presents many challenges and will need substantial financial support if it is to develop at a rate sufficient to cope with developments in nano-technology. PMID:22662021

IRIS Toxicological Review of Ammonia (Interagency Science ...

EPA Pesticide Factsheets

On June 1, 2012, the draft Toxicological Review of Ammonia and the draft 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. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia and the charge to external peer reviewers, are posted on this site. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

IRIS Toxicological Review of n-Butanol (Interagency Science ...

EPA Pesticide Factsheets

On September 8, 2011, the Toxicological Review of n-Butanol (External Review Draft) was 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, 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 with EPA's response and the interagency science consultation draft of the IRIS Toxicological Review of n-Butanol and the charge to external peer reviewers are posted on this site. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for n-butanol. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Overview of data and conceptual approaches for derivation of quantitative structure-activity relationships for ecotoxicological effects of organic chemicals.

PubMed

Bradbury, Steven P; Russom, Christine L; Ankley, Gerald T; Schultz, T Wayne; Walker, John D

2003-08-01

The use of quantitative structure-activity relationships (QSARs) in assessing potential toxic effects of organic chemicals on aquatic organisms continues to evolve as computational efficiency and toxicological understanding advance. With the ever-increasing production of new chemicals, and the need to optimize resources to assess thousands of existing chemicals in commerce, regulatory agencies have turned to QSARs as essential tools to help prioritize tiered risk assessments when empirical data are not available to evaluate toxicological effects. Progress in designing scientifically credible QSARs is intimately associated with the development of empirically derived databases of well-defined and quantified toxicity endpoints, which are based on a strategic evaluation of diverse sets of chemical structures, modes of toxic action, and species. This review provides a brief overview of four databases created for the purpose of developing QSARs for estimating toxicity of chemicals to aquatic organisms. The evolution of QSARs based initially on general chemical classification schemes, to models founded on modes of toxic action that range from nonspecific partitioning into hydrophobic cellular membranes to receptor-mediated mechanisms is summarized. Finally, an overview of expert systems that integrate chemical-specific mode of action classification and associated QSAR selection for estimating potential toxicological effects of organic chemicals is presented.

Long-term fate of depleted uranium at Aberdeen and Yuma Proving Grounds: Human health and ecological risk assessments

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

Ebinger, M.H.; Beckman, R.J.; Myers, O.B.

1996-09-01

The purpose of this study was to evaluate the immediate and long-term consequences of depleted uranium (DU) in the environment at Aberdeen Proving Ground (APG) and Yuma Proving Ground (YPG) for the Test and Evaluation Command (TECOM) of the US Army. Specifically, we examined the potential for adverse radiological and toxicological effects to humans and ecosystems caused by exposure to DU at both installations. We developed contaminant transport models of aquatic and terrestrial ecosystems at APG and terrestrial ecosystems at YPG to assess potential adverse effects from DU exposure. Sensitivity and uncertainty analyses of the initial models showed the portionsmore » of the models that most influenced predicted DU concentrations, and the results of the sensitivity analyses were fundamental tools in designing field sampling campaigns at both installations. Results of uranium (U) isotope analyses of field samples provided data to evaluate the source of U in the environment and the toxicological and radiological doses to different ecosystem components and to humans. Probabilistic doses were estimated from the field data, and DU was identified in several components of the food chain at APG and YPG. Dose estimates from APG data indicated that U or DU uptake was insufficient to cause adverse toxicological or radiological effects. Dose estimates from YPG data indicated that U or DU uptake is insufficient to cause radiological effects in ecosystem components or in humans, but toxicological effects in small mammals (e.g., kangaroo rats and pocket mice) may occur from U or DU ingestion. The results of this study were used to modify environmental radiation monitoring plans at APG and YPG to ensure collection of adequate data for ongoing ecological and human health risk assessments.« less

IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Toxicogenomics concepts and applications to study hepatic effects of food additives and chemicals

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

Stierum, Rob; Heijne, Wilbert; Kienhuis, Anne

2005-09-01

Transcriptomics, proteomics and metabolomics are genomics technologies with great potential in toxicological sciences. Toxicogenomics involves the integration of conventional toxicological examinations with gene, protein or metabolite expression profiles. An overview together with selected examples of the possibilities of genomics in toxicology is given. The expectations raised by toxicogenomics are earlier and more sensitive detection of toxicity. Furthermore, toxicogenomics will provide a better understanding of the mechanism of toxicity and may facilitate the prediction of toxicity of unknown compounds. Mechanism-based markers of toxicity can be discovered and improved interspecies and in vitro-in vivo extrapolations will drive model developments in toxicology. Toxicologicalmore » assessment of chemical mixtures will benefit from the new molecular biological tools. In our laboratory, toxicogenomics is predominantly applied for elucidation of mechanisms of action and discovery of novel pathway-supported mechanism-based markers of liver toxicity. In addition, we aim to integrate transcriptome, proteome and metabolome data, supported by bioinformatics to develop a systems biology approach for toxicology. Transcriptomics and proteomics studies on bromobenzene-mediated hepatotoxicity in the rat are discussed. Finally, an example is shown in which gene expression profiling together with conventional biochemistry led to the discovery of novel markers for the hepatic effects of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole.« less

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).

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.

Acute Toxicological Study of Ampicillin Anhydrate Microcapsules in Sprague-Dawley Rats.

DTIC Science & Technology

This document contains the results of an acute toxicological study to determine the toxicologic potential of ampicillin anhydrate microcapsules on...various organs of the rat. Keywords: Wound treatment; Antibiotic microcapsule ; Controlled release; Experimental data; Tables data. (aw)

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

Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach, September 2005

DTIC Science & Technology

2007-12-01

there are no reliable alternatives to animal testing in the determination of toxicity. QSARs are only as reliable as the corroborating toxicological ...2) QSAR approaches can also be used to estimate toxicological impact. Toxicity QSAR models can often predict many toxicity parameters without... Toxicology Study No. 87-XE-03N3-05, Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach, September 2005 1

Using zebrafish in systems toxicology for developmental toxicity testing.

PubMed

Nishimura, Yuhei; Inoue, Atsuto; Sasagawa, Shota; Koiwa, Junko; Kawaguchi, Koki; Kawase, Reiko; Maruyama, Toru; Kim, Soonih; Tanaka, Toshio

2016-01-01

With the high cost and the long-term assessment of developmental toxicity testing in mammals, the vertebrate zebrafish has become a useful alternative model organism for high-throughput developmental toxicity testing. Zebrafish is also very favorable for the 3R perspective in toxicology; however, the methodologies used by research groups vary greatly, posing considerable challenges to integrative analysis. In this review, we discuss zebrafish developmental toxicity testing, focusing on the methods of chemical exposure, the assessment of morphological abnormalities, housing conditions and their effects on the production of healthy embryos, and future directions. Zebrafish as a systems toxicology model has the potential to elucidate developmental toxicity pathways, and to provide a sound basis for human health risk assessments. © 2015 Japanese Teratology Society.

Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century

PubMed Central

Xia, Tian; Zhu, Yifang; Mu, Lina; Zhang, Zuo-Feng; Liu, Sijin

2016-01-01

Abstract Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM2.5) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM2.5 concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM2.5. In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future. PMID:28649460

Transparency and translation of science in a modern world.

PubMed

Grandjean, Philippe; Ozonoff, David

2013-08-27

The co-Editors-in-Chief of Environmental Health respond to an unusual initiative taken by editors of 14 toxicology journals to influence pending decisions by the European Commission to establish a framework for regulating chemicals that pose a hazard to normal function of the endocrine system. This initiative is also the subject of this Commentary in this journal by authors who recently reviewed the subject and who point out inaccuracies in the toxicology editors' critique. The dispute is about potential public policy development, rather than on science translation and research opportunities and priorities. The toxicology journal editors recommend that chemicals be examined in depth one by one, ignoring modern achievements in biomedical research that would allow new understanding of the effects of classes of toxic substances in complex biological systems. Concerns about policy positions framed as scientific ones are especially important in a time with shrinking public support for biomedical research affects priorities. In such a setting, conflict of interest declarations are important, especially in research publications that address issues of public concern and where financial and other interests may play a role. Science relies on trust, and reasonable disclosure of financial or other potential conflicts is therefore essential. This need has been emphasized by recent discoveries of hidden financial conflicts in publications in toxicology journals, thus misleading readers and the public about the safety of particular industrial products. The transparency provided by Environmental Health includes open access and open peer review, with reader access to reviews, including the identity of reviewers and their statements on possible conflicts of interest. However, the editors of the 14 toxicology journals did not provide any information on potential conflicts of interest, an oversight that needs to be corrected.

Global warming and environmental contaminants in aquatic organisms: the need of the etho-toxicology approach.

PubMed

Manciocco, Arianna; Calamandrei, Gemma; Alleva, Enrico

2014-04-01

Environmental contaminants are associated with a wide spectrum of pathological effects. Temperature increase affects ambient distribution and toxicity of these chemicals in the water environment, representing a potentially emerging problem for aquatic species with short-, medium- and long-term repercussions on human health through the food chain. We assessed peer-reviewed literature, including primary studies, review articles and organizational reports available. We focused on studies concerning toxicity of environmental pollutants within a global warming scenario. Existing knowledge on the effects that the increase of water temperature in a contaminated situation has on physiological mechanisms of aquatic organisms is presented. Altogether we consider the potential consequences for the human beings due to fish and shellfish consumption. Finally, we propose an etho-toxicological approach to study the effects of toxicants in conditions of thermal increase, using aquatic organisms as experimental models under laboratory controlled conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Potentiating toxicological interaction of single-walled carbon nanotubes with dissolved metals.

PubMed

Al-Shaeri, Majed; Ahmed, Dina; McCluskey, Fiona; Turner, Gavin; Paterson, Lynn; Dyrynda, Elisabeth A; Hartl, Mark G J

2013-12-01

The present study explored the ecotoxicology of single-walled carbon nanotubes (SWCNTs) and their likely interaction with dissolved metals, with a focus on the effect of in vivo exposure in marine mussels. Any nano-scale effects were negated by the tendency of uncoated SWCNTs to agglomerate in water, particularly with high ionic strength as is the case in estuarine and full-strength seawater. However, SWCNTs, in combination with natural organic matter, remained suspended in seawater for long enough to become available to filter-feeding mussels, leading to their concentration on and increased contact with gill epithelia during exposure. For the first time, the authors describe a potentiating toxicological effect, expressed as DNA strand breaks obtained using the comet assay, on divalent metals afforded by negatively charged SWCNT agglomerates in seawater at concentrations as low as 5 µg L⁻¹. This is supported by the observation that SWCNTs alone were only toxic at concentrations ≥100 µg L⁻¹ and that the SWCNT-induced DNA damage was correlated with oxidative stress only in the absence of metals. If these laboratory experiments are confirmed in the natural environment, the present results will have implications for the understanding of the role of carbon nanotubes in environmental metal dynamics, toxicology, and consequently, regulatory requirements. © 2013 SETAC.

Nanotechnology: toxicologic pathology.

PubMed

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

2013-02-01

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

Nanotechnology: Toxicologic Pathology

PubMed Central

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

2015-01-01

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

Microbial degradation and toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine.

PubMed

Khan, Muhammad Imran; Lee, Jaejin; Park, Joonhong

2012-10-01

In the present work, current knowledge on the potential fate, microbial degradation, and toxicity of hexahydro- 1,3,5-trinitro-1,3,5-triazine (RDX) was thoroughly reviewed, focusing on the toxicological assessment of a variety of potential RDX degradation pathways in bacteria and fungi. The present review on microbial degradation pathways and toxicities of degradation intermediates suggests that, among aerobic RDX degradation pathways, the one via denitration may be preferred in a toxicological perspective, and that among anaerobic pathways, those forming 4- nitro-2,4-diazabutanal (NDAB) via ring cleavage of 1-nitroso- 3,5-dinitro-1,3,5-triazinane (MNX) may be toxicologically advantageous owing to its potential mineralization under partial or complete anoxic conditions. These findings provide important information on RDX-degrading microbial pathways, toxicologically most suitable to be stimulated in contaminated fields.

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.

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.

The Role of Epigenomics in Aquatic Toxicology.

PubMed

Brander, Susanne M; Biales, Adam D; Connon, Richard E

2017-10-01

Over the past decade, the field of molecular biology has rapidly incorporated epigenetic studies to evaluate organism-environment interactions that can result in chronic effects. Such responses arise from early life stage stress, the utilization of genetic information over an individual's life time, and transgenerational inheritance. Knowledge of epigenetic mechanisms provides the potential for a comprehensive evaluation of multigenerational and heritable effects from environmental stressors, such as contaminants. Focused studies have provided a greater understanding of how many responses to environmental stressors are driven by epigenetic modifiers. We discuss the promise of epigenetics and suggest future research directions within the field of aquatic toxicology, with a particular focus on the potential for identifying key heritable marks with consequential impacts at the organism and population levels. Environ Toxicol Chem 2017;36:2565-2573. © 2017 SETAC. © 2017 SETAC.

International Space Station Air Quality Assessed According to Toxicologically-Grouped Compounds

NASA Technical Reports Server (NTRS)

James, John T.; Limero, Thomas F.; Beck, Steve; Cheng, Patti F.; deVera, Vanessa J.; Hand, Jennifer; Macatangay, Ariel

2010-01-01

Scores of compounds are found in the International Space Station (ISS) atmospheric samples that are returned to the Johnson Space Center Toxicology Laboratory for analysis. Spacecraft Maximum Allowable Concentrations (SMACs) are set with the view that each compound is present as if there were no other compounds present. In order to apply SMACs to the interpretation of the analytical data, the toxicologist must employ some method of combining the potential effects of the aggregate of compounds found in the atmospheric samples. The simplest approach is to assume that each quantifiable compound has the potential for some effect in proportion to the applicable SMAC, and then add all the proportions. This simple paradigm disregards the fact that most compounds have potential to adversely affect only a few physiological systems, and their effects would be independent rather than additive. An improved approach to dealing with exposure to mixtures is to add the proportions only for compounds that adversely affect the same physiological system. For example, toxicants that cause respiratory irritation are separated from those that cause neurotoxicity or cardio-toxicity. Herein we analyze ISS air quality data according to toxicological groups with a view that this could be used for understanding any crew symptoms occurring at the time of the sample acquisition. In addition, this approach could be useful in post-flight longitudinal surveys where the flight surgeon may need to identify post-flight, follow-up medical studies because of on-orbit exposures that target specific physiological systems.

International Space Station Air Quality Assessed According to Toxicologically-Grouped Compounds

NASA Technical Reports Server (NTRS)

James, John T.; Limero, Tom; DeVera, Vanessa; Cheng, Patti; Hand, Jennifer; Macatangay, Ariel; Beck, Steve

2009-01-01

Scores of compounds are found in the International Space Station (ISS) atmospheric samples that are returned to the Johnson Space Center Toxicology Laboratory for analysis. Spacecraft Maximum Allowable Concentrations (SMACs) are set with the view that each compound is present as if there were no other compounds present. In order to apply SMACs to the interpretation of the analytical data, the toxicologist must employ some method of combining the potential effects of the aggregate of compounds found in the atmospheric samples. The simplest approach is to assume that each quantifiable compound has the potential for some effect in proportion to the applicable SMAC, and then add all the proportions. This simple paradigm disregards the fact that most compounds have potential to adversely affect only a few physiological systems, and their effects would be independent rather than additive. An improved approach to dealing with exposure to mixtures is to add the proportions only for compounds that adversely affect the same physiological system. For example, toxicants that cause respiratory irritation are separated from those that cause neurotoxicity or cardio-toxicity. Herein we analyze ISS air quality data according to toxicological groups with a view that this could be used for understanding any crew symptoms occurring at the time of the sample. In addition, this approach could be useful in post-flight longitudinal surveys where the flight surgeon may need to identify post-flight, follow-up medical studies because of on-orbit exposures that target specific physiological systems.

Results of a Wildlife Toxicology Workshop held by the Smithsonian Institution ? Identification and prioritization of problem statements

USGS Publications Warehouse

Grim, K.C.; Fairbrother, A.; Monfort, S.; Tan, S.; Rattner, B.A.; Gerould, S.; Beasley, V.; Aguirre, A.; Rowles, T.

2007-01-01

On March 13-15, 2007 nearly 50 scientists and administrators from the US and Canada participated in a Smithsonian-sponsored Wildlife Toxicology Workshop. Invitees were from academic, government, conservation and the private organizations and were selected to represent the diverse disciplines that encompass wildlife toxicology. The workshop addressed scientific and policy issues, strengths and weaknesses of current research strategies, interdisciplinary and science-based approaches in the study of complex contaminant issues, mechanisms for disseminating data to policy-makers, and the development of a partner network to meet the challenges facing wildlife toxicology over the next decade. Prior to the meeting, participants were asked to submit issues they deemed to be of highest concern which shaped four thematic groups for discussion: Wildlife Toxicology in Education, Risk Assessment, Multiple Stressors/Complex Mixtures, and Sub-Lethal to Population-Level Effects. From these discussion groups, 18 problem statements were developed and prioritized outlining what were deemed the most important issues to address now and into the future. Along with each problem statement participants developed potential solutions and action steps geared to move each issue forward. The workshop served as a stepping stone for action in the field of wildlife toxicology. These problem statements and the resulting action items are presented to the inter-disciplinary wildlife toxicology community for adoption, and future work and action items in these areas are encouraged. The workshop outcome looks to generate conversation and collaboration that will lead to the development of innovative research, future mechanisms for funding, workshops, working groups, and listserves within the wildlife toxicology community.

Use of automated monitoring to assess behavioral toxicology in fish: Linking behavior and physiology

USGS Publications Warehouse

Brewer, S.K.; DeLonay, A.J.; Beauvais, S.L.; Little, E.E.; Jones, S.B.

1999-01-01

We measured locomotory behaviors (distance traveled, speed, tortuosity of path, and rate of change in direction) with computer-assisted analysis in 30 day posthatch rainbow trout (Oncorhynchus mykiss) exposed to pesticides. We also examined cholinesterase inhibition as a potential endpoint linking physiology and behavior. Sublethal exposure to chemicals often causes changes in swimming behavior, reflecting alterations in sensory and motor systems. Swimming behavior also integrates functions of the nervous system. Rarely are the connections between physiology and behavior made. Although behavior is often suggested as a sensitive, early indicator of toxicity, behavioral toxicology has not been used to its full potential because conventional methods of behavioral assessment have relied on manual techniques, which are often time-consuming and difficult to quantify. This has severely limited the application and utility of behavioral procedures. Swimming behavior is particularly amenable to computerized assessment and automated monitoring. Locomotory responses are sensitive to toxicants and can be easily measured. We briefly discuss the use of behavior in toxicology and automated techniques used in behavioral toxicology. We also describe the system we used to determine locomotory behaviors of fish, and present data demonstrating the system's effectiveness in measuring alterations in response to chemical challenges. Lastly, we correlate behavioral and physiological endpoints.

Confounders in interpreting pathology for safety and risk assessment

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

Wolf, Douglas C.; Mann, Peter C.

2005-02-01

The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must bemore » reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.« less

Toxicology as a nanoscience? – Disciplinary identities reconsidered

PubMed Central

Kurath, Monika; Maasen, Sabine

2006-01-01

Toxicology is about to establish itself as a leading scientific discipline in addressing potential health effects of materials on the nanosize level. Entering into a cutting-edge field, has an impact on identity-building processes within the involved academic fields. In our study, we analyzed the ways in which the entry into the field of nanosciences impacts on the formation of disciplinary identities. Using the methods of qualitative interviews with particle toxicologists in Germany, Holland, Switzerland and the USA, we could demonstrate that currently, toxicology finds itself in a transitional phase. The development of its disciplinary identity is not yet clear. Nearly all of our interview partners stressed the necessity of repositioning toxicology. However, they each suggested different approaches. While one part is already propagandizing the establishment of a new discipline – 'nanotoxicology'- others are more reserved and are demanding a clear separation of traditional and new research areas. In phases of disciplinary new-orientation, research communities do not act consistently. Rather, they establish diverse options. By expanding its disciplinary boundaries, participating in new research fields, while continuing its previous research, and only vaguely defining its topics, toxicology is feeling its way into the new fields without giving up its present self-conception. However, the toxicological research community is also discussing a new disciplinary identity. Within this, toxicology could develop from an auxiliary into a constitutive position, and take over a basic role in the cognitive, institutional and social framing of the nanosciences. PMID:16646961

The Feasibility and Acceptability of Google Glass for Teletoxicology Consults.

PubMed

Chai, Peter R; Babu, Kavita M; Boyer, Edward W

2015-09-01

Teletoxicology offers the potential for toxicologists to assist in providing medical care at remote locations, via remote, interactive augmented audiovisual technology. This study examined the feasibility of using Google Glass, a head-mounted device that incorporates a webcam, viewing prism, and wireless connectivity, to assess the poisoned patient by a medical toxicology consult staff. Emergency medicine residents (resident toxicology consultants) rotating on the toxicology service wore Glass during bedside evaluation of poisoned patients; Glass transmitted real-time video of patients' physical examination findings to toxicology fellows and attendings (supervisory consultants), who reviewed these findings. We evaluated the usability (e.g., quality of connectivity and video feeds) of Glass by supervisory consultants, as well as attitudes towards use of Glass. Resident toxicology consultants and supervisory consultants completed 18 consults through Glass. Toxicologists viewing the video stream found the quality of audio and visual transmission usable in 89 % of cases. Toxicologists reported their management of the patient changed after viewing the patient through Glass in 56 % of cases. Based on findings obtained through Glass, toxicologists recommended specific antidotes in six cases. Head-mounted devices like Google Glass may be effective tools for real-time teletoxicology consultation.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR BERYLLIUM AND COMPOUNDS

EPA Science Inventory

EPA's assessment of the noncancer health effects and carcinogenic potential of Beryllium was added to the IRIS database in 1998. The IRIS program is updating the IRIS assessment for Beryllium. This update will incorporate health effects information published since the last assess...

IRIS Toxicological Review and Summary Documents for Tertiary Amyl Ethyl Ether (Taee)

EPA Science Inventory

This is EPA's first assessment of the noncancer health effects and carcinogenic potential of tertiary amyl ethyl ether (TAEE). The IRIS program is preparing an assessment that will incorporate health effects information available for TAEE, and current risk assessment methods. T...

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.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 1,2,3-TRICHLOROPROPANE

EPA Science Inventory

EPA's assessment of the noncancer health effects and carcinogenic potential of 1,2,3-trichloropropane (TCP) was added to the IRIS database in 1990. The IRIS program is updating the IRIS assessment for TCP. This update will incorporate health effects information published since t...

Enantioselective environmental toxicology of chiral pesticides.

PubMed

Ye, Jing; Zhao, Meirong; Niu, Lili; Liu, Weiping

2015-03-16

The enantioselective environmental toxic effect of chiral pesticides is becoming more important. As the industry develops, increasing numbers of chiral insecticides and herbicides will be introduced into use, potentially posing toxic effects on nontarget living beings. Chiral pesticides, including herbicides such as acylanilides, phenoxypropanoic acids, and imidazolinones, and insecticides such as synthetic pyrethroids, organophosphates, and DDT often behave enantioselectively during agricultural use. These compounds also pose unpredictable enantioselective ecological threats to nontarget living beings and/or humans, affecting the food chain and entire ecosystems. Thus, to investigate the enantioselective toxic effects of chiral insecticides and herbicides is necessary during environmental protection. The environmental toxicology of chiral pesticides, especially the findings obtained from studies conducted in our laboratory during the past 10 years, is reviewed.

Toxicology in the 21st Century (Tox21)

EPA Pesticide Factsheets

Tox21 researchers aim to develop better toxicity assessment methods to quickly and efficiently test whether certain chemical compounds have the potential to disrupt processes in the human body that may lead to negative health effects.

Toxicology Testing in the 21st Century (Tox21)

EPA Pesticide Factsheets

Tox21 researchers aim to develop better toxicity assessment methods to quickly and efficiently test whether certain chemical compounds have the potential to disrupt processes in the human body that may lead to negative health effects.

Hazardous properties and toxicological update of mercury: From fish food to human health safety perspective.

PubMed

Okpala, Charles Odilichukwu R; Sardo, Giacomo; Vitale, Sergio; Bono, Gioacchino; Arukwe, Augustine

2017-04-10

The mercury (Hg) poisoning of Minamata Bay of Japan widely activated a global attention to Hg toxicity and its potential consequences to the aquatic ecosystem and human health. This has resulted to an increased need for a dynamic assembly, contextualization, and quantification of both the current state-of-the-art and approaches for understanding the cause-and-effect relationships of Hg exposure. Thus, the objective of this present review is to provide both hazardous toxic properties and toxicological update of Hg, focusing on how it ultimately affects the aquatic biota to potentially produce human health effects. Primarily, we discussed processes that relate to Hg exposure, including immunological aspects and risk assessment, vulnerability, toxicokinetics, and toxicodynamics, using edible fish, swordfish (Xiphias gladius), as a model. In addition, we summarized available information about Hg concentration limits set by different governmental agencies, as recognized by national and international standardization authorities.

Solvents and Parkinson disease: A systematic review of toxicological and epidemiological evidence

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

Lock, Edward A., E-mail: e.lock@ljmu.ac.uk; Zhang, Jing; Checkoway, Harvey

2013-02-01

Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia nigra. The causes of PD remain poorly understood, although environmental toxicants may play etiologic roles. Solvents are widespread neurotoxicants present in the workplace and ambient environment. Case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE). Animal toxicology studies have been conducted on various organic solvents, with some, including TCE, demonstrating potential for inducing nigral system damage. However, a confirmed animal model of solvent-induced PD has not been developed.more » Numerous epidemiologic studies have investigated potential links between solvents and PD, yielding mostly null or weak associations. An exception is a recent study of twins indicating possible etiologic relations with TCE and other chlorinated solvents, although findings were based on small numbers, and dose–response gradients were not observed. At present, there is no consistent evidence from either the toxicological or epidemiologic perspective that any specific solvent or class of solvents is a cause of PD. Future toxicological research that addresses mechanisms of nigral damage from TCE and its metabolites, with exposure routes and doses relevant to human exposures, is recommended. Improvements in epidemiologic research, especially with regard to quantitative characterization of long-term exposures to specific solvents, are needed to advance scientific knowledge on this topic. -- Highlights: ► The potential for organic solvents to cause Parkinson's disease has been reviewed. ► Twins study suggests etiologic relations with chlorinated solvents and Parkinson's. ► Animal studies with TCE showed potential to cause damage to dopaminergic neurons. ► Need to determine if effects in animals are relevant to human exposure levels.« less

Systems Toxicology: From Basic Research to Risk Assessment

PubMed Central

2014-01-01

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment. PMID:24446777

Systems toxicology: from basic research to risk assessment.

PubMed

Sturla, Shana J; Boobis, Alan R; FitzGerald, Rex E; Hoeng, Julia; Kavlock, Robert J; Schirmer, Kristin; Whelan, Maurice; Wilks, Martin F; Peitsch, Manuel C

2014-03-17

Systems Toxicology is the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization. Society demands increasingly close scrutiny of the potential health risks associated with exposure to chemicals present in our everyday life, leading to an increasing need for more predictive and accurate risk-assessment approaches. Developing such approaches requires a detailed mechanistic understanding of the ways in which xenobiotic substances perturb biological systems and lead to adverse outcomes. Thus, Systems Toxicology approaches offer modern strategies for gaining such mechanistic knowledge by combining advanced analytical and computational tools. Furthermore, Systems Toxicology is a means for the identification and application of biomarkers for improved safety assessments. In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional and apical end points) is deciphered. Mathematical models are then built to describe these processes in a quantitative manner. The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes. This perspective integrates current knowledge regarding bioanalytical approaches, computational analysis, and the potential for improved risk assessment.

Applications of flow cytometry to toxicological mycotoxin effects in cultured mammalian cells: a review.

PubMed

Juan-García, Ana; Manyes, Lara; Ruiz, María-José; Font, Guillermina

2013-06-01

This review gives an overview of flow cytometry applications to toxicological studies of several physiological target sites of mycotoxins on different mammalian cell lines. Mycotoxins are secondary metabolites of fungi that may be present in food, feed, air and water. The increasing presence of mycotoxins in crops, their wide distribution in the food chain, and their potential for toxicity demonstrate the need for further knowledge. Flow cytometry has become a valuable tool in mycotoxin studies in recent years for the rapid analysis of single cells in a mixture. In toxicology, the power of these methods lies in the possibility of determining a wide range of cell parameters, providing valuable information to elucidate cell growth and viability, metabolic activity, mitochondrial membrane potential and membrane integrity mechanisms. There are studies using flow cytometry technique on Alternaria, Aspergillus, Fusarium and Penicillium mycotoxins including information about cell type, assay conditions and functional parameters. Most of the studies collected in the literature are on deoxynivalenol and zearalenone mycotoxins. Cell cycle analysis and apoptosis are the processes more widely investigated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Occupational hazards of missile operations with special regard to the hydrazine propellants.

PubMed

Back, K C; Carter, V L; Thomas, A A

1978-04-01

The second generation of ballistic missiles and boosters, characterized by increased range and quick reaction capability, required the development of new high-energy storage propellants. This exploration led to the introduction of hydrazine (Hz), monomethylhydrazine (MMH), and 1,1-dimethylhydrazine (UDMH) into the USAF inventory. These compounds are all storable, noncryogenic, high-energy fuels which may be used alone or in combination as mixed amine fuels. Early toxicology experiments were to produce data on acute and subacute effects of the propellants in order to set standards for test and operational procedures to protect propellant handlers. The early work indicated that, despite similar chemical characteristics, there were marked differences between the compounds in terms of toxicological mechanisms. Since the propellant systems have been used for some 15 years, recent emphasis on toxicology has been centered on the more chronic effects and on an increasing body of evidence from animal experiments that the compounds may possess oncogenic potential as well as chronic systemic effects. This paper addresses itself to data leading up to current occupational standards.

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.

Concordance between self-reported substance use and toxicology among HIV-infected and uninfected at risk youth.

PubMed

Nichols, Sharon L; Lowe, Amanda; Zhang, Xinrui; Garvie, Patricia A; Thornton, Sarah; Goldberger, Bruce A; Hou, Wei; Goodenow, Maureen M; Sleasman, John W

2014-01-01

Substance use by youth living with HIV (YLWH) is a concern, given potential interactions with virus-associated immune suppression and adverse effects on risk behaviors, neurocognition, and adherence. Self-report substance use measures provide efficient cost-effective assessments. Analyses describe self-reported substance use among YLWH and examine agreement with toxicology assays. Seventy-eight youth age 18-24 years (87% male, 71% African-American) with behaviorally acquired HIV-1 infection and 55 uninfected youth completed the Alcohol, Smoking, and Substance Involvement Screening Test to assess drug use frequency, including tobacco, marijuana, cocaine, and alcohol, over the prior three months. Elisa-based toxicology assays were used to detect 27 substances in plasma. Chi-square tests compared substance use between YLWH and uninfected youth; Kappa statistics compared agreement between self-report and toxicology. YLWH reported marijuana (49%), tobacco (56%), and alcohol (87%) use, with 20%, 28% and 3% reporting daily use of each substance, respectively; other substance use was uncommon. Uninfected youth reported less tobacco use but otherwise similar substance use. All youth who reported daily use of marijuana or tobacco had positive plasma toxicology results, while concordance decreased with less frequent self-reported use. Among youth reporting no substance use, few tested positive (4% YLWH, 2% uninfected youth for cannabis; 8%YLWH for tobacco). Youth report high rates of marijuana, tobacco, and alcohol use. Concordance between self-report and toxicology for marijuana and tobacco use, particularly for daily users, supports self-report as a valid indicator of substance use in research studies of youth with or without HIV-1 infection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Potential Developmental and Early Life Health Effects of Nanomaterials: Data Gaps and Research Needs for Risk Assessment

EPA Science Inventory

Although research examining the toxicology of nanomaterials has been ongoing for many years, early studies largely focus on respiratory effects, and are limited by lack of appropriate dose metrics and a limited understanding of the role of the physicochemical properties of nanoma...

Screening for an Allergic Response to 2nd Generation Biofuel Sources

EPA Science Inventory

Abstract for March 2014 Society of Toxicology Annual Meeting The use of cellulosic biofuels crops can potentially reduce our carbon footprint. However, they may have unintended ecological and health effects such as increased competitiveness and allergenicity...

COMPUTATIONAL TOXICOLOGY: AN APPROACH FOR PRIORITIZING CHEMICAL RISK ASSESSMENTS

EPA Science Inventory

Characterizing toxic effects for industrial chemicals carries the challenge of focusing resources on the greatest potential risks for human health and the environment. The union of molecular modeling, bioinformatics and simulation of complex systems with emerging technologies suc...

Toxicological evaluation of clay minerals and derived nanocomposites: a review.

PubMed

Maisanaba, Sara; Pichardo, Silvia; Puerto, María; Gutiérrez-Praena, Daniel; Cameán, Ana M; Jos, Angeles

2015-04-01

Clays and clay minerals are widely used in many facets of our society. This review addresses the main clays of each phyllosilicate groups, namely, kaolinite, montmorillonite (Mt) and sepiolite, placing special emphasis on Mt and kaolinite, which are the clays that are more frequently used in food packaging, one of the applications that are currently exhibiting higher development. The improvements in the composite materials obtained from clays and polymeric matrices are remarkable and well known, but the potential toxicological effects of unmodified or modified clay minerals and derived nanocomposites are currently being investigated with increased interest. In this sense, this work focused on a review of the published reports related to the analysis of the toxicological profile of commercial and novel modified clays and derived nanocomposites. An exhaustive review of the main in vitro and in vivo toxicological studies, antimicrobial activity assessments, and the human and environmental impacts of clays and derived nanocomposites was performed. From the analysis of the scientific literature different conclusions can be derived. Thus, in vitro studies suggest that clays in general induce cytotoxicity (with dependence on the clay, concentration, experimental system, etc.) with different underlying mechanisms such as necrosis/apoptosis, oxidative stress or genotoxicity. However, most of in vivo experiments performed in rodents showed no clear evidences of systemic toxicity even at doses of 5000mg/kg. Regarding to humans, pulmonary exposure is the most frequent, and although clays are usually mixed with other minerals, they have been reported to induce pneumoconiosis per se. Oral exposure is also common both intentionally and unintentionally. Although they do not show a high toxicity through this pathway, toxic effects could be induced due to the increased or reduced exposure to mineral elements. Finally, there are few studies about the effects of clay minerals on wildlife, with laboratory trials showing contradictory outcomes. Clay minerals have different applications in the environment, thus with a strict control of the concentrations used, they can provide beneficial uses. Despite the extensive number of reports available, there is also a need of systematic in vitro-in vivo extrapolation studies, with still scarce information on toxicity biomarkers such as inmunomodulatory effects or alteration of the genetic expression. In conclusion, a case by case toxicological evaluation is required taking into account that different clays have their own toxicological profiles, their modification can change this profile, and the potential increase of the human/environmental exposure to clay minerals due to their novel applications. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

PubMed

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

2013-04-01

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

Geometry of carbon nanotubes and mechanisms of phagocytosis and toxic effects.

PubMed

Harik, Vasyl Michael

2017-05-05

A review of in vivo and in vitro toxicological studies of the potential toxic effects of carbon nanotubes is presented along with the analysis of experimental data and a hypothesis about the nanotube-asbestos similarity. Developments of the structure-activity paradigm have been reviewed along with the size effects and the classification of carbon nanotubes into eleven distinct classes (e.g., the high aspect ratio nanotubes, thick multi-wall nanotubes and short nanotubes). Scaling analysis of similarities between different classes of carbon nanotubes and asbestos fibers in the context of their potential toxicity and the efficiency of phagocytosis has been reviewed. The potential toxic effects of carbon nanotubes have been characterized by their normalized length, their aspect ratio and other parameters related to their inhalability, engulfment by macrophages and the effectiveness of phagocytosis. Geometric scaling parameters and the classification of carbon nanotubes are used to develop an updated parametric map for the extrapolation of the potential toxic effects resulting from the inhalation of long and short carbon nanotubes. An updated parametric map has been applied to the evaluation of the efficiency of phagocytosis involving distinct classes of carbon nanotubes. A critical value of an important nondimensional parameter characterizing the efficiency of phagocytosis for different nanotubes is presented along with its macrophage-based normalization. The present evaluation of the potential toxicological effects of the high aspect ratio carbon nanotubes is found to be in the agreement with other available studies and earlier scaling analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Cavallin et al 2015

EPA Pesticide Factsheets

This study demonstrates the potential of whole-mount in situ hybridization (WISH), in conjunction with quantitative real-time polymerase chain reaction (QPCR) assays, to examine the mechanistic basis of the effects of toxicants on early-lifestage fathead minnows. Specifically, fathead minnow embryos were exposed to the environmentally-relevant estrogen receptor agonist, estrone, and the data show that: (1) the estrogen-responsive gene transcripts esr1, vtg, and cyp19b can be up-regulated in very early-lifestages of the fathead minnow, (2) WISH methods developed for zebrafish can also be applied successfully to fathead minnows, and (3) WISH has potential to be a useful tool for toxicological studies pertaining to early-lifestage development in the fathead minnow. This type of mechanistic information relative to spatial distribution of gene expression is important in determining potential biological pathways that may be impacted by targeted chemicals and the development of associated adverse outcome pathways.This dataset is associated with the following publication:Cavallin, J., A. Schroeder, K. Jensen , D. Villeneuve , B. Blackwell, K. Carlson, M. Kahl , C. LaLone , E. Randolph , and G. Ankley. Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 169: 19-26, (2015).

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.

IRIS Toxicological Review of Ammonia Noncancer Inhalation (Final Report)

EPA Science Inventory

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the ...

DEVELOPING BIOMARKERS FOR MYCOTOXIN EXPOSURE AND EFFECT

USDA-ARS?s Scientific Manuscript database

The purpose of this presentation is to briefly summarize the toxicology and current state of biomarker development for commercially important mycotoxins with a focus on their potential usefulness in farm animals. Combining information about known exposure, clinical indicators and biomarkers will pro...

NITROGEN DIOXIDE, PULMONARY FUNCTION, AND RESPIRATORY DISEASE

EPA Science Inventory

Concern as to the toxicity of the oxides of nitrogen has been frequently expressed in clinical and toxicological literature. Oxides of nitrogen are highly reactive compounds and suggest toxic effects on biological systems. The earliest evidence for potential damage to man occurre...

Downloadable Computational Toxicology Data

EPA Pesticide Factsheets

EPA’s computational toxicology research generates data that investigates the potential harm, or hazard of a chemical, the degree of exposure to chemicals as well as the unique chemical characteristics. This data is publicly available here.

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.

INHALATIONAL EXPOSURE TO CARBONYL SULFIDE (COS) PRODUCES BRAIN LESIONS AND ALTERED BRAINSTEM AUDITORY (BAER) AND SOMATOSENSORY (SEP) EVOKED POTENTIALS IN FISHCER 344N RATS.

EPA Science Inventory

Because of the amount of carbonyl sulfide (COS) emissions and the lack of toxicological data, COS was listed in the Clean Air Act of 1990 as a Hazardous Air Pollutant. In 1999 COS was nominated by the US EPA to the National Toxicology Program for additional toxicological investig...

Adverse outcome pathways: a concise introduction for toxicologists

PubMed Central

Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

2018-01-01

Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

Mind the Gap! A Journey towards Computational Toxicology.

PubMed

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Altomare, Cosimo Damiano; Carotti, Angelo; Catto, Marco; Cellamare, Saverio; Gadaleta, Domenico; Lattanzi, Gianluca; Leonetti, Francesco; Pisani, Leonardo; Stefanachi, Angela; Trisciuzzi, Daniela; Nicolotti, Orazio

2016-09-01

Computational methods have advanced toxicology towards the development of target-specific models based on a clear cause-effect rationale. However, the predictive potential of these models presents strengths and weaknesses. On the good side, in silico models are valuable cheap alternatives to in vitro and in vivo experiments. On the other, the unconscious use of in silico methods can mislead end-users with elusive results. The focus of this review is on the basic scientific and regulatory recommendations in the derivation and application of computational models. Attention is paid to examine the interplay between computational toxicology and drug discovery and development. Avoiding the easy temptation of an overoptimistic future, we report our view on what can, or cannot, realistically be done. Indeed, studies of safety/toxicity represent a key element of chemical prioritization programs carried out by chemical industries, and primarily by pharmaceutical companies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

Predictive Models and Computational Toxicology

EPA Science Inventory

Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The ToxCast computational toxicology research program was l...

NEW PUBLIC DATA AND INTERNET RESOURCES IMPACTING PREDICTIVE TOXICOLOGY.

EPA Science Inventory

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve predictive capabilities in toxicology.

DIOXIN 2003 BOSTON

EPA Science Inventory

DIOXON 2003 BOSTON
SESSION SUMMARY REPORT

Toxicology of BFRs

This oral session is comprised of seven presentations dealing with the potential health effects of BFRs. Talks involve both in vivo and in vitro studies in mice, rats, and cultured cells, and are from...

TOXCAST: A TOOL FOR THE PRIORITIZATION OF CHEMICALS FOR TOXICOLOGICAL EVALUATION

EPA Science Inventory

Due to various legislatiave mandates, the US EPA is faced with evaluating the potential of tens of thousands of chemicals (e.g., high production volume chemicals, pestididal inerts, and drinking water contaminants) to cause adverse human health & environmental effects.

IRIS Toxicological Review of Trimethylbenzenes (Final Report)

EPA Science Inventory

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Trimethylbenzenes (TMBs). This assessment addresses the potential non-cancer and cancer human health effects from long-term exposure to TMBs. Now final, this assessment will be the first IRIS a...

Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) Assay: Book Chapter

EPA Science Inventory

There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An adher...

Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay-Book Chapter*

EPA Science Inventory

There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An adhere...

Toxicological Evaluation of Realistic Emission Source Aerosols (TERESA): Introduction and overview

PubMed Central

Godleski, John J.; Rohr, Annette C.; Kang, Choong M.; Diaz, Edgar A.; Ruiz, Pablo A.; Koutrakis, Petros

2013-01-01

Determining the health impacts of sources and components of fine particulate matter (PM2.5) is an important scientific goal. PM2.5 is a complex mixture of inorganic and organic constituents that are likely to differ in their potential to cause adverse health outcomes. The Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) study focused on two PM sources—coal-fired power plants and mobile sources—and sought to investigate the toxicological effects of exposure to emissions from these sources. The set of papers published here document the power plant experiments. TERESA attempted to delineate health effects of primary particles, secondary (aged) particles, and mixtures of these with common atmospheric constituents. TERESA involved withdrawal of emissions from the stacks of three coal-fired power plants in the United States. The emissions were aged and atmospherically transformed in a mobile laboratory simulating downwind power plant plume processing. Toxicological evaluations were carried out in laboratory rats exposed to different emission scenarios with extensive exposure characterization. The approach employed in TERESA was ambitious and innovative. Technical challenges included the development of stack sampling technology that prevented condensation of water vapor from the power plant exhaust during sampling and transfer, while minimizing losses of primary particles; development and optimization of a photochemical chamber to provide an aged aerosol for animal exposures; development and evaluation of a denuder system to remove excess gaseous components; and development of a mobile toxicology laboratory. This paper provides an overview of the conceptual framework, design, and methods employed in the study. PMID:21639692

Experimental designs and risk assessment in combination toxicology: panel discussion.

PubMed

Henschler, D; Bolt, H M; Jonker, D; Pieters, M N; Groten, J P

1996-01-01

Advancing our knowledge on the toxicology of combined exposures to chemicals and implementation of this knowledge in guidelines for health risk assessment of such combined exposures are necessities dictated by the simple fact that humans are continuously exposed to a multitude of chemicals. A prerequisite for successful research and fruitful discussions on the toxicology of combined exposures (mixtures of chemicals) is the use of defined terminology implemented by an authoritative international body such as, for example, the International Union of Pure and Applied Chemistry (IUPAC) Toxicology Committee. The extreme complexity of mixture toxicology calls for new research methodologies to study interactive effects, taking into account limited resources. Of these methodologies, statistical designs and mathematical modelling of toxicokinetics and toxicodynamics seem to be most promising. Emphasis should be placed on low-dose modelling and experimental validation. The scientifically sound so-called bottom-up approach should be supplemented with more pragmatic approaches, focusing on selection of the most hazardous chemicals in a mixture and careful consideration of the mode of action and possible interactive effects of these chemicals. Pragmatic approaches may be of particular importance to study and evaluate complex mixtures; after identification of the 'top ten' (most risky) chemicals in the mixture they can be examined and evaluated as a defined (simple) chemical mixture. In setting exposure limits for individual chemicals, the use of an additional safety factor to compensate for potential increased risk due to simultaneous exposure to other chemicals, has no clear scientific justification. The use of such an additional factor is a political rather than a scientific choice.

Baseline knowledge of potential pet toxins among the US general public.

PubMed

Young, Natalie; Royal, Kenneth; Lovee, Bryan; Davidson, Gigi

2018-05-16

In 2014, the American Society for the Prevention of Cruelty toAnimals Animal Poison Control Center fielded more than 167,000cases of potential nonhuman animal toxicosis. Concomitantly, thereremain limited free and reputable veterinary toxicology resourcesavailable for companion-animal (pet) caregivers (owners) seekingassistance and advice about potentially harmful exposures inanimals. The objective of this study was to assess pet toxicantknowledge among a representative sample of Americans andgauge the need for additional toxicology resources. The studyinvolved a survey designed to capture participants' ability to identifypotential animal toxicants and what resource they would use ifan accidental toxic ingestion occurred. Participants were ableto correctly identify 52% of potential pet toxins. Women, olderparticipants and participants from the South expressed moreconcern about each potential pet poison. Approximately halfof participants indicated they would consult a veterinarian andwhereas most others indicated they would search the Internet formore information about pet toxicology. The findings suggest moreveterinary poisoning education is needed for pet owners to be ableto accurately distinguish potential pet toxicants from nontoxicants.

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

Problem Definition Studies on Potential Environmental Pollutants. VII. Physical, Chemical, Toxicological, and Biological Properties of DDT and Its Derivatives

DTIC Science & Technology

1979-06-01

WORDS (C-enlnuo on reverse side If n*co*or and Identlif by block numbe) Amphibians Birds DDT Man Analytical Methods Carcinogenesis Fish Metabolism ...18 Bioaccumulation and the Food Chain .. .. .. .. .. . .19 Effects on Terrestrial Animals. .. ........ .. .... 21 Effects on...Aquatic Organisms .. . . .. .. .. .. .. . .25 Effects on Microorganisms .. ........... .. .... 41 VI. STANDARDS AND CRITERIA FOR DDT

IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

EPA Pesticide Factsheets

In September 2016, EPA finalized the IRIS assessment of Ammonia (Noncancer Inhalation). The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release in June 2016. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ammonia (Noncancer Inhalation) are posted on this site. Note: No major science comments were received on the Interagency Science Discussion Draft. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Understanding the toxicological potential of aerosol organic compounds using informatics based screening

NASA Astrophysics Data System (ADS)

Topping, David; Decesari, Stefano; Bassan, Arianna; Pavan, Manuela; Ciacci, Andrea

2016-04-01

Exposure to atmospheric particulate matter is responsible for both short-term and long-term adverse health effects. So far, all efforts spent in achieving a systematic epidemiological evidence of specific aerosol compounds determining the overall aerosol toxicity were unsuccessful. The results of the epidemiological studies apparently conflict with the laboratory toxicological analyses which have highlighted very different chemical and toxicological potentials for speciated aerosol compounds. Speciation remains a problem, especially for organic compounds: it is impossible to conduct screening on all possible molecular species. At the same time, research on toxic compounds risks to be biased towards the already known compounds, such as PAHs and dioxins. In this study we present results from an initial assessment of the use of in silico methods (i.e. (Q)SAR, read-across) to predict toxicity of atmospheric organic compounds including evaluation of applicability of a variety of popular tools (e.g. OECD QSAR Toolbox) for selected endpoints (e.g. genotoxicity). Compounds are categorised based on the need of new experimental data for the development of in silico approaches for toxicity prediction covering this specific chemical space, namely the atmospheric aerosols. Whilst only an initial investigation, we present recommendations for continuation of this work.

Delivering The Benefits of Chemical-Biological Integration in ...

EPA Pesticide Factsheets

Abstract: Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intention of this research program is to quickly evaluate thousands of chemicals for potential risk but with much reduced cost relative to historical approaches. This work involves computational and data driven approaches including high-throughput screening, modeling, text-mining and the integration of chemistry, exposure and biological data. We have developed a number of databases and applications that are delivering on the vision of developing a deeper understanding of chemicals and their effects on exposure and biological processes that are supporting a large community of scientists in their research efforts. This presentation will provide an overview of our work to bring together diverse large scale data from the chemical and biological domains, our approaches to integrate and disseminate these data, and the delivery of models supporting computational toxicology. This abstract does not reflect U.S. EPA policy. Presentation at ACS TOXI session on Computational Chemistry and Toxicology in Chemical Discovery and Assessement (QSARs).

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.

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

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

Henshel, D.S.

1996-12-31

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

Chemical residence time and hydrological conditions influence fipronil reduction in vegetated aquatic mesocosms

USDA-ARS?s Scientific Manuscript database

Fipronil, a phenyl-pyrazole insecticide and its metabolites (Fipronil sulfone, sulfide and desulfinyl) is often used in rice production agriculture with elevated runoff concentrations and loads having potential toxicological effects on downstream aquatic environments. This study evaluated two specie...

AOPs and Biomarkers: Bridging High Throughput Screening and Regulatory Decision Making

EPA Science Inventory

As high throughput screening (HTS) plays a larger role in toxicity testing, camputational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models designed to quantify potential adverse effects based on HTS data will b...

Toxicogenomic responses of nanotoxicity in Daphnia magna exposed to silver nitrate and coated silver nanoparticles

EPA Science Inventory

Applications for silver nanomaterials in consumer products are rapidly expanding, creating an urgent need for toxicological examination of the exposure potential and ecological effects of silver nanoparticles (AgNPs). The integration of genomic techniques into environmental toxic...

A germination bioassay as a toxicological screening system for studying the effects of potential prodrugs of naproxen.

PubMed

Gonzalez-de la Parra, M; Ramos-Mundo, C; Jimenez-Estrada, M; Ponce-de Leon, C; Castillo, R; Tejeda, V; Cuevas, K G; Enriquez, R G

1998-01-01

A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus. 1998 FRAME.

Hormonally active phytochemicals and vertebrate evolution.

PubMed

Lambert, Max R; Edwards, Thea M

2017-06-01

Living plants produce a diversity of chemicals that share structural and functional properties with vertebrate hormones. Wildlife species interact with these chemicals either through consumption of plant materials or aquatic exposure. Accumulating evidence shows that exposure to these hormonally active phytochemicals (HAPs) often has consequences for behavior, physiology, and fecundity. These fitness effects suggest there is potential for an evolutionary response by vertebrates to HAPs. Here, we explore the toxicological HAP-vertebrate relationship in an evolutionary framework and discuss the potential for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals that influence fitness. We lay out several hypotheses about HAPs and provide a path forward to test whether plant-derived chemicals influence vertebrate reproduction and evolution. Studies of phytochemicals with direct impacts on vertebrate reproduction provide an obvious and compelling system for studying evolutionary toxicology. Furthermore, an understanding of whether animal populations evolve in response to HAPs could provide insightful context for the study of rapid evolution and how animals cope with chemical agents in the environment.

IRIS Toxicological Review of Tetrahydrofuran (THF) ...

EPA Pesticide Factsheets

EPA is releasing the draft report, Toxicological Review of Tetrahydrofuran, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for tetrahydrofuran. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

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).

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

[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

Military deployment toxicology: a program manager's perspective.

PubMed

Knechtges, P L

2000-02-01

The Persian Gulf War drew attention to the potential hazards of chemicals that personnel may encounter during military operations and deployments overseas. During the War, the oil well fires of Kuwait highlighted the military threat of industrial chemicals in the area of operations. Following the War, the occurrence of Gulf War Illnesses brought home concerns and suspicions regarding "low level" and "mixed" exposures to chemicals. The public's concern and attention resulted in numerous institutional responses to the real and perceived problems of health risks during military deployments. These institutional responses ranged in scope from a Presidential Review Directive to the initiative known as the Deployment Toxicology Research, Development, Testing and Evaluation (RDT&E) Program. Most institutions, however, seem to agree that additional research is needed to assess the health risks from chemical exposures during military deployments. Establishing and managing an effective RDT&E program in risk assessment for deployed forces is a challenging enterprise. The Deployment Toxicology RDT&E Program was conceived utilizing the military's acquisition framework, an effective methodology with a proven record of fielding of new technologies. Based on a series of structured meetings with military representatives that would utilize new risk assessment tools, a hierarchical set of plans was developed to identify and prioritize end products. The challenge ahead for the Deployment Toxicology RDT&E Program is to execute these plans, provide the necessary oversight, and transition the results into successful product development.

Toxicological features of maleilated polyflavonoids from Pinus radiata (D. Don.) as potential functional additives for biomaterials design.

PubMed

García, Danny E; Medina, Paulina A; Zúñiga, Valentina I

2017-11-01

Polyflavonoids from Pinus radiata (D. Don.) are an abundant natural oligomers highly desirable as renewable chemicals. However, structural modification of polyflavonoids is a viable strategy in order to use such polyphenols as macrobuilding-blocks for biomaterial design. Polyflavonoids were esterified with three five-member cyclic anhydrides (maleic, itaconic, and citraconic) at 20 °C during 24 h in order to diversify physicochemical-, and biological-properties for agricultural, and food-packaging applications. In addition, the influence of the chemical modification, as well as the chemical structure of the grafting on toxicological features was evaluated. Structural features of derivatives were analyzed by spectroscopy (FT-IR and 1 H-NMR), and the degree of substitution was calculated. Toxicological profile was assessed by using three target species in a wide range of concentration (0.01-100 mgL - 1 ). Effect of polyflavonoids on the growth rate (Selenastrum capricornutum), mortality (Daphnia magna), and germination and radicle length (Lactuca sativa) was determined. Chemical modification affects the toxicological profile on the derivatives in a high extent. Results described remarkable differences in function of the target specie. The bioassays indicate differences of the polyflavonoids toxicological profile associated to the chemical structure of the grafting. Results allowed conclude that polyflavonoids from pine bark show slight toxic properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Need for, and the Role of the Toxicological Chemist in the Design of Safer Chemicals.

PubMed

DeVito, Stephen C

2018-02-01

During the past several decades, there has been an ever increasing emphasis for designers of new commercial (nonpharmaceutical) chemicals to include considerations of the potential impacts a planned chemical may have on human health and the environment as part of the design of the chemical, and to design chemicals such that they possess the desired use efficacy while minimizing threats to human health and the environment. Achievement of this goal would be facilitated by the availability of individuals specifically and formally trained to design such chemicals. Medicinal chemists are specifically trained to design and develop safe and clinically efficacious pharmaceutical substances. No such formally trained science hybrid exists for the design of safer commercial (nonpharmaceutical) chemicals. This article describes the need for and role of the "toxicological chemist," an individual who is formally trained in synthetic organic chemistry, biochemistry, physiology, toxicology, environmental science, and in the relationships between structure and commercial use efficacy, structure and toxicity, structure and environmental fate and effects, and global hazard, and trained to integrate this knowledge to design safer commercially efficacious chemicals. Using examples, this article illustrates the role of the toxicological chemist in designing commercially efficacious, safer chemical candidates. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by a US Government employee and is in the public domain in the US.

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

Day and night variation in chemical composition and toxicological responses of size segregated urban air PM samples in a high air pollution situation

NASA Astrophysics Data System (ADS)

Jalava, P. I.; Wang, Q.; Kuuspalo, K.; Ruusunen, J.; Hao, L.; Fang, D.; Väisänen, O.; Ruuskanen, A.; Sippula, O.; Happo, M. S.; Uski, O.; Kasurinen, S.; Torvela, T.; Koponen, H.; Lehtinen, K. E. J.; Komppula, M.; Gu, C.; Jokiniemi, J.; Hirvonen, M.-R.

2015-11-01

Urban air particulate pollution is a known cause for adverse human health effects worldwide. China has encountered air quality problems in recent years due to rapid industrialization. Toxicological effects induced by particulate air pollution vary with particle sizes and season. However, it is not known how distinctively different photochemical activity and different emission sources during the day and the night affect the chemical composition of the PM size ranges and subsequently how it is reflected to the toxicological properties of the PM exposures. The particulate matter (PM) samples were collected in four different size ranges (PM10-2.5; PM2.5-1; PM1-0.2 and PM0.2) with a high volume cascade impactor. The PM samples were extracted with methanol, dried and thereafter used in the chemical and toxicological analyses. RAW264.7 macrophages were exposed to the particulate samples in four different doses for 24 h. Cytotoxicity, inflammatory parameters, cell cycle and genotoxicity were measured after exposure of the cells to particulate samples. Particles were characterized for their chemical composition, including ions, element and PAH compounds, and transmission electron microscopy (TEM) was used to take images of the PM samples. Chemical composition and the induced toxicological responses of the size segregated PM samples showed considerable size dependent differences as well as day to night variation. The PM10-2.5 and the PM0.2 samples had the highest inflammatory potency among the size ranges. Instead, almost all the PM samples were equally cytotoxic and only minor differences were seen in genotoxicity and cell cycle effects. Overall, the PM0.2 samples had the highest toxic potential among the different size ranges in many parameters. PAH compounds in the samples and were generally more abundant during the night than the day, indicating possible photo-oxidation of the PAH compounds due to solar radiation. This was reflected to different toxicity in the PM samples. Some of the day to night difference may have been caused also by differing wind directions transporting air masses from different emission sources during the day and the night. The present findings indicate the important role of the local particle sources and atmospheric processes on the health related toxicological properties of the PM. The varying toxicological responses evoked by the PM samples showed the importance of examining various particle sizes. Especially the detected considerable toxicological activity by PM0.2 size range suggests they're attributable to combustion sources, new particle formation and atmospheric processes.

Size-dependent cytotoxicity of yttrium oxide nanoparticles on primary osteoblasts in vitro

NASA Astrophysics Data System (ADS)

Zhou, Guoqiang; Li, Yunfei; Ma, Yanyan; Liu, Zhu; Cao, Lili; Wang, Da; Liu, Sudan; Xu, Wenshi; Wang, Wenying

2016-05-01

Yttrium oxide nanoparticles are an excellent host material for the rare earth metals and have high luminescence efficiency providing a potential application in photodynamic therapy and biological imaging. In this study, the effects of yttrium oxide nanoparticles with four different sizes were investigated using primary osteoblasts in vitro. The results demonstrated that the cytotoxicity generated by yttrium oxide nanoparticles depended on the particle size, and smaller particles possessed higher toxicological effects. For the purpose to elucidate the relationship between reactive oxygen species generation and cell damage, cytomembrane integrity, intracellular reactive oxygen species level, mitochondrial membrane potential, cell apoptosis rate, and activity of caspase-3 in cells were then measured. Increased reactive oxygen species level was also observed in a size-dependent way. Thus, our data demonstrated that exposure to yttrium oxide nanoparticles resulted in a size-dependent cytotoxicity in cultured primary osteoblasts, and reactive oxygen species generation should be one possible damage pathway for the toxicological effects produced by yttrium oxide particles. The results may provide useful information for more rational applications of yttrium oxide nanoparticles in the future.

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)

Cadmium-containing nanoparticles: Perspectives on pharmacology and toxicology of quantum dots

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

Rzigalinski, Beverly A.; Strobl, Jeannine S.

2009-08-01

The field of nanotechnology is rapidly expanding with the development of novel nanopharmaceuticals that have potential for revolutionizing medical treatment. The rapid pace of expansion in this field has exceeded the pace of pharmacological and toxicological research on the effects of nanoparticles in the biological environment. The development of cadmium-containing nanoparticles, known as quantum dots, show great promise for treatment and diagnosis of cancer and targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. However, information on pharmacology and toxicology of quantum dots needs much further development, making it difficult to assess the risksmore » associated with this new nanotechnology. Further, nanotechnology poses yet another risk for toxic cadmium, which will now enter the biological realm in nano-form. In this review, we discuss cadmium-containing quantum dots and their physicochemical properties at the nano-scale. We summarize the existing work on pharmacology and toxicology of cadmium-containing quantum dots and discuss perspectives in their utility in disease treatment. Finally, we identify critical gaps in our knowledge of cadmium quantum dot toxicity, and how these gaps need to be assessed to enable quantum dot nanotechnology to transit safely from bench to bedside.« less

IRIS Toxicological Review of Benzene (Noncancer Effects) (1998 External Review Draft)

EPA Science Inventory

Benzene is a widely used as an industrial solvent, an intermediate in chemical synthesis of commercial products, and a component of gasoline. The potential for human exposure via inhalation, dermal, and oral routes is great under environmental and occupational situations. The U.S...

Developmental neurotoxicity testing in vitro: Models for assessing chemical effects on neurite outgrowth

EPA Science Inventory

In vitro models may be useful for the rapid toxicological screening of large numbers of chemicals for their potential to produce toxicity. Such screening could facilitate prioritization of resources needed for in vivo toxicity testing towards those chemicals most likely to resul...

Measuring Physicochemical Properties to Inform the Scope of Existing QSAR/QSPR Models (SOT annual meeting)

EPA Science Inventory

Chemical structures and their properties are important for determining their potential toxicological effects, toxicokinetics, and route of exposure. These data are needed to prioritize thousands of environmental chemicals, but are often lacking. In order to fill data gaps, robust...

CONCENTRATION AND TREATMENT OF DRINKING WATERS IN THE FOUR LAB STUDY

EPA Science Inventory

The purpose of the four lab study was to address concerns related to potential health effects from exposure to complex mixtures of DBPs that cannot be addressed directly from toxicological studies of individual disinfection by-products (DBPs) or simple DBP mixtures. In order to ...

IRIS TOXICOLOGICAL REVIEW OF BENZENE (NONCANCER EFFECTS)

EPA Science Inventory

Benzene, also known as benzol, is widely used as an industrial solvent, as an intermediate in chemical syntheses, and as a component of gasoline; hence, the potential for human exposure is great. The emphasis of this document is a discussion of the noncancer adverse healt...

20180318 - Rapid collection of experimental physicochemical property data to inform various models and testing methods (ACS Spring)

EPA Science Inventory

In order to determine the potential toxicological effects, toxicokinetics, and route(s) of exposure for chemicals, their structures and corresponding physicochemical properties are required. With this data, the risk for thousands of environmental chemicals can be prioritized. How...

Photochemical Conversion of Surrogate Emissions for Use in Toxicological Studies: Role of Particulate- and Gas-Phase Products

EPA Science Inventory

The production of photochemical atmospheres under controlled conditions in an irradiated chamber permits the manipulation of a variety of parameters that influences resulting air pollutant chemistry and potential biological effects. To date no studies have examined how contrastin...

PERSPECTIVES ON THE CONCERN FOR AND MANAGEMENT OF PRENATAL CHEMICAL EXPOSURE AND POSTNATAL EFFECTS

EPA Science Inventory

This paper was presented as the introduction to a session on the history and epidemiology of prenatal chemical exposure. lthough teratology and developmental toxicology had its experimental beginnings in the early part of this century, the potential for human developmental toxici...

Public Databases Supporting Computational Toxicology

EPA Science Inventory

A major goal of the emerging field of computational toxicology is the development of screening-level models that predict potential toxicity of chemicals from a combination of mechanistic in vitro assay data and chemical structure descriptors. In order to build these models, resea...

Recent Developments in Toxico-Cheminformatics: A New Frontier for Predictive Toxicology

EPA Science Inventory

Efforts to improve public access to chemical toxicity information resources, coupled with new high-throughput screening (HTS) data and efforts to systematize legacy toxicity studies, have the potential to significantly improve predictive capabilities in toxicology. Important rec...

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...

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.

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.

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

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

Tian, Dayong; Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000; Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptorsmore » of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two generic points of toxicological mechanism were elucidated.« less

High risk of respiratory diseases in children in the fire period in Western Amazon.

PubMed

Silva, Pãmela Rodrigues de Souza; Ignotti, Eliane; Oliveira, Beatriz Fátima Alves de; Junger, Washington Leite; Morais, Fernando; Artaxo, Paulo; Hacon, Sandra

2016-06-10

To analyze the toxicological risk of exposure to ozone (O3) and fine particulate matter (PM2.5) among schoolchildren.. Toxicological risk assessment was used to evaluate the risk of exposure to O3 and PM2.5 from biomass burning among schoolchildren aged six to 14 years, residents of Rio Branco, Acre, Southern Amazon, Brazil. We used Monte Carlo simulation to estimate the potential intake dose of both pollutants. During the slash-and-burn periods, O3 and PM2.5 concentrations reached 119.4 µg/m3 and 51.1 µg/m3, respectively. The schoolchildren incorporated medium potential doses regarding exposure to O3 (2.83 μg/kg.day, 95%CI 2.72-2.94). For exposure to PM2.5, we did not find toxicological risk (0.93 μg/kg.day, 95%CI 0.86-0.99). The toxicological risk for exposure to O3 was greater than 1 for all children (QR = 2.75; 95%CI 2.64-2.86). Schoolchildren were exposed to high doses of O3 during the dry season of the region. This posed a toxicological risk, especially to those who had previous diseases.

Incorporating exposure information into the toxicological prioritization index decision support framework

EPA Science Inventory

The Toxicological Prioritization Index (ToxPi) decision support framework was previously developed to facilitate incorporation of diverse data to prioritize chemicals based on potential hazard. This ToxPi index was demonstrated by considering results of bioprofiling related to po...

The startle response and toxicology: Methods, use and interpretation.

EPA Science Inventory

The startle response (SR) is a sensory-evoked motor reflex that has been used successfully in toxicology for decades. Advantages of this procedure include: rapidly objective measurement of a defined neural circuit, measurement of habituation of the response, and a high potential ...

Billing and reimbursement for a bedside toxicology service at a tertiary care academic center during its first fiscal year.

PubMed

Wiegand, Timothy J; Crane, Peter W; Kamali, Michael; Reif, Marilynn; Wratni, Rose; Montante, Ronald; Loveland, Tracey

2015-03-01

A bedside toxicology consult service may improve clinical care, facilitate patient clearance and disposition, and result in potential cost savings for poisoning exposures. Despite this, there is scant data regarding economic feasibility for such a service. Previously published information suggests low hourly reimbursement at approximately $26.00/h at the bedside for toxicology consultations. A bedside toxicology consultant service was initiated in 2011. Coverage was available 24 h a day for 50 out of 52 weeks. Bedside rounding on toxicology consult patients was available 6/7 days per week. The practice is associated with >800 bed teaching institution in a large upstate NY region with elements of urban and suburban practice. Demographic and billing data was collected for all patients consulted upon from July 1, 2011 to June 31, 2012. In charges of $514,941 were generated during the period of data collection. Monthly average was $42,912. Net reimbursement of charges was 29 % of overall charges at $147,792. In terms of total encounters, net collection rate in which something was reimbursed or "paid" against charges for that encounter was 82.6 % of all encounters at 999/1,210. Average encounter time for inpatients, including critical care, was 1.05 h, and the average time spent for outpatients was 1.18 h. Reimbursement rates appear higher than previously reported. Revenue generated from reimbursement from toxicology consultation can result in recouping a substantial portion of a toxicologist's salary or potentially fund fellowship positions and salaries or toxicology division infrastructure.

The Surface Microlayer: Review of Literature and Evaluation of Potential Effects of Dredge Activities in Puget Sound.

DTIC Science & Technology

1987-01-01

Heyrand. 1975. Polonium - 210 - Its vertical oceanic transport by zoo- plankton metabolic activity. Marine Chemistry 3:105-110. Collins, J. 1974. Oil and...Toxicology Environ. Health 7:991-1000. Hose, J.E., J.B. Hannah, D. Dijulio, M.L. Landolt, B.S. Miller, W.T. Iwaoka, and S.P. Felton. 1982. Effects of benzo(a...A184 885 THE SURFACE MICROLAVER, REVIEWJ OF LITERATURE AND 1/2 EVALUATION OF POTENTIAL EFFECTS OF DREDGE ACTIVITIES IN PUGET SOUND(U) EVANS-HAMILTON

The U.S. EPA's ToxCast Chemical Screening Program and Predictive Modeling of Toxicity

EPA Science Inventory

The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A

EPA Science Inventory

The National Toxicology Program (NTP)1 established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the CERHR is to provide timely, unbiased, scientifically sound evaluations of the potential for adverse effects on reproduction...

COMPARISON OF CHEMICAL SCREENING AND RANKING APPROACHES: THE WASTE MINIMIZATION PRIORITIZATION TOOL VERSUS TOXIC EQUIVALENCY POTENTIALS

EPA Science Inventory

Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a compar...

TRANSCRIPTIONAL PROFILES IN LIVER FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

EPA Science Inventory

Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study (Allen et al. 2006) under...

Considerations in Use of the EPA’s ToxCast Data for Environmental Toxicology (SETAC)

EPA Science Inventory

The US EPA has developed the ToxCast program to prioritize chemicals for selective toxicity testing. ToxCast relies on extensive bioactivity profiling using a panel of biochemical and cellular assays that measure chemicals effects on potential molecular initiating events and key ...

Space Toxicology

NASA Technical Reports Server (NTRS)

James, John T.

2011-01-01

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

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

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

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

1995-09-01

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

Comparison of the cardiac electrophysiology and general toxicology of two formulations of intravenous amiodarone in dogs.

PubMed

Cushing, Daniel J; Cooper, Warren D; Gralinski, Michael R; Lipicky, Raymond J; Kudenchuk, Peter J; Kowey, Peter R

2009-09-01

Intravenous amiodarone (AIV) must be administered slowly after dilution to avoid hypotension, which is due to the cosolvents polysorbate 80 and benzyl alcohol used in its formulation. PM101 is a formulation of amiodarone devoid of these cosolvents, which enables bolus administration. We evaluated any potential toxicity or exaggerated adverse cardiac electrophysiologic effects of PM101 compared with AIV and control. Beagle dogs were treated with the human-equivalent amiodarone loading dose (2.14 mg/kg) with PM101 (bolus push) or AIV (10 min infusion in the toxicology study and bolus push in the electrophysiology study) followed by maintenance infusion (0.014 mg kg(-1) min(-1) through 6 h followed by 0.007 mg kg(-1) min(-1) through 14 days) or a control. General toxicology was assessed in conscious dogs over 14 days. Cardiac electrophysiology was assessed in a separate cohort of anesthetized dogs during the first 20 min of dosing. In the toxicology study, dosing in all animals in the AIV group was terminated within 17 min of initiation due to a severe hypersensitivity reaction. There were no acute adverse clinical signs in the PM101 or control groups. There were no significant effects on body weight or ECG parameters, and no adverse histomorphologic changes were seen in dogs that received PM101 or AIV. No significant exaggerated cardiac electrophysiologic effects of the approved doses PM101 or AIV were observed. PM101 may represent a formulation of intravenous amiodarone that could be administered rapidly without dilution in the setting of life-threatening cardiac arrhythmias.

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...

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

Toxicology of tetramethyltin and other organometals used in photovoltaic cell manufacture

NASA Astrophysics Data System (ADS)

Hamilton, L. D.; Medeiros, W. H.; Moskowitz, P. D.; Rybicka, K.

1988-07-01

In photovoltaic cell fabrication, organometals (alkyl metals) may be used in such processes as metalorganic chemical vapor deposition, transparent contact oxide deposition, doping, and ion implantation. Although these compounds offer potential performance advantages over earth metals and possibly greater safety in handling than metal hydrides, they are not without risk to health and property. Most organometals can ignite spontaneously in air. Some also react violently with water. Oxidation by-products from these reactions are hazardous to health. Of the organometals used in photovoltaic cell fabrication, only the toxicology of organotins (triethyl-, trimethyl- and tetramethyltin) was studied extensively. In mammalian systems, tetramethyltin is rapidly dealkylated to trimethyltin. Although tin was classified by some investigators as an essential trace element, the effects of organotin compounds on humans are poorly known. Animal studies show that the most prominent effects of trimethyltin are on the central nervous system. Several observations of poisoning were reported; effects ranged from reversible neurologic disorders to death. Limited available data suggest that humans respond to single acute doses and more alarmingly to repeated sub-toxic doses, suggesting a cumulative effect. Toxicologic properties of diethyltelluride also were evaluated in animal experiments. The compound had toxic effects on the blood, liver, kidney, heart, and skin. Based on these studies and others of related compounds (e.g., methylmercury, tributyltin) extreme caution should be exercised in using organometal compounds in photovoltaic cell manufacturing.

The EPA Comptox Chemistry Dashboard: A Web-Based Data Integration Hub for Toxicology Data (SOT)

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

The adverse outcome pathway concept: a pragmatic tool in toxicology.

PubMed

Vinken, Mathieu

2013-10-04

Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The profound effect of harmful cyanobacterial blooms: From food-web and management perspectives.

PubMed

Šulčius, Sigitas; Montvydienė, Danguolė; Mazur-Marzec, Hanna; Kasperovičienė, Jūratė; Rulevičius, Rokas; Cibulskaitė, Živilė

2017-12-31

Sustainable and effective water management plans must have a reliable risk assessment strategies for harmful cyanobacterial blooms (HABs) that would enable timely decisions to be made, thus avoiding the trespassing of ecological thresholds, leading to the collapse of ecosystem structure and function. Such strategies are usually based on cyanobacterial biomass and/or on the monitoring of known toxins, which may, however, in many cases, under- or over-represent the actual toxicity of the HAB. Therefore, in this study, by the application of growth-inhibition assays using different bacteria, algae, zooplankton and fish species, we assessed the toxicological potential of two cyanobacterial blooms that differed in total cyanobacterial biomass, species composition and cyanopeptide profiles. We demonstrated that neither cyanobacterial community composition nor its relative abundance, nor indeed concentrations of known toxins reflected the potential risk of HAB based on growth-inhibition assays. We discuss our findings in the context of food-web dynamics and ecosystem management, and suggest that toxicological tests should constitute a key element in the routine monitoring of water bodies so as to prevent under-/over-estimation of potential HAB risk for both ecosystem and public health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

PubMed

2012-04-01

Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

Induced pluripotent stem cells in hematology: current and future applications

PubMed Central

Focosi, D; Amabile, G; Di Ruscio, A; Quaranta, P; Tenen, D G; Pistello, M

2014-01-01

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation. PMID:24813079

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

Selkirk, J.K.

The National Toxicology Program (NTP) was organized to support national public health programs by initiating research designed to understand the physiological, metabolic, and genetic basis for chemical toxicity. The primary mandated responsibilities of NTP were in vivo and vitro toxicity testing of potentially hazardous chemicals; broadening the spectrum of toxicological information on known hazardous chemicals; validating current toxicological assay systems as well as developing new and innovative toxicity testing technology; and rapidly communicating test results to government agencies with regulatory responsibilities and to the medical and scientific communities. 2 figs.

INTEGRATED CHEMICAL INFORMATION TECHNOLOGIES ...

EPA Pesticide Factsheets

A central regulatory mandate of the Environmental Protection Agency, spanning many Program Offices and issues, is to assess the potential health and environmental risks of large numbers of chemicals released into the environment, often in the absence of relevant test data. Models for predicting potential adverse effects of chemicals based primarily on chemical structure play a central role in prioritization and screening strategies yet are highly dependent and conditional upon the data used for developing such models. Hence, limits on data quantity, quality, and availability are considered by many to be the largest hurdles to improving prediction models in diverse areas of toxicology. Generation of new toxicity data for additional chemicals and endpoints, development of new high-throughput, mechanistically relevant bioassays, and increased generation of genomics and proteomics data that can clarify relevant mechanisms will all play important roles in improving future SAR prediction models. The potential for much greater immediate gains, across large domains of chemical and toxicity space, comes from maximizing the ability to mine and model useful information from existing toxicity data, data that represent huge past investment in research and testing expenditures. In addition, the ability to place newer “omics” data, data that potentially span many possible domains of toxicological effects, in the broader context of historical data is the means for opti

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

Computational toxicology using the OpenTox application programming interface and Bioclipse

PubMed Central

2011-01-01

Background Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. Findings This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. Conclusions A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers. PMID:22075173

Clinical and anatomic pathology effects of serial blood sampling in rat toxicology studies, using conventional or microsampling methods.

PubMed

Caron, Alexis; Lelong, Christine; Bartels, T; Dorchies, O; Gury, T; Chalier, Catherine; Benning, Véronique

2015-08-01

As a general practice in rodent toxicology studies, satellite animals are used for toxicokinetic determinations, because of the potential impact of serial blood sampling on toxicological endpoints. Besides toxicological and toxicokinetic determinations, blood samples obtained longitudinally from a same animal may be used for the assessment of additional parameters (e.g., metabolism, pharmacodynamics, safety biomarkers) to maximize information that can be deduced from rodents. We investigated whether removal of up to 6 × 200 μL of blood over 24h can be applied in GLP rat toxicology studies without affecting the scientific outcome. 8 week-old female rats (200-300 g) were dosed for up to 1 month with a standard vehicle and subjected or not (controls) to serial blood sampling for sham toxicokinetic/ancillary determinations, using miniaturized methods allowing collection of 6 × 50, 100 or 200 μL over 24h. In-life endpoints, clinical pathology parameters and histopathology of organs sensitive to blood volume reduction were evaluated at several time points after completion of sampling. In sampled rats, minimal and reversible changes in red blood cell mass (maximally 15%) and subtle variations in liver enzymes, fibrinogen and neutrophils were not associated with any organ/tissue macroscopic or microscopic correlate. Serial blood sampling (up to 6 × 200 μL over 24h) is compatible with the assessment of standard toxicity endpoints in adult rats. Copyright © 2015 Elsevier Inc. All rights reserved.

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

The Role of Toxicological Science in Meeting the Challenges and Opportunities of Hydraulic Fracturing

EPA Science Inventory

We briefly describe how toxicology can inform the discussion and debate of the merits of hydraulic fracturing by providing information on the potential toxicity of the chemical and physical agents associated with this process, individually and in combination. We consider upstream...

The ToxCast Chemical Prioritization Program at the US EPA (UCLA Molecular Toxicology Program)

EPA Science Inventory

To meet the needs of chemical regulators reviewing large numbers of data-poor chemicals for safety, the EPA's National Center for Computational Toxicology is developing a means of efficiently testing thousands of compounds for potential toxicity. High-throughput bioactivity profi...

Investigating Impact Metrics for Performance for the US EPA National Center for Computational Toxicology (ACS Fall meeting)

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

Anatomy of a decision III: Evaluation of national disposal at sea program action level efficacy considering 2 chemical action levels.

PubMed

Apitz, Sabine E; Vivian, Chris; Agius, Suzanne

2017-11-01

The potential performance (i.e., ability to separate nontoxic from toxic sediments) of a range of international Disposal at Sea (DaS) chemical Action Levels (ALs) was compared using a sediment chemical and toxicological database. The use of chemistry alone (without the use of further lines of evidence) did not perform well at reducing costs and protecting the environment. Although some approaches for interpreting AL1 results are very effective at filtering out the majority of acutely toxic sediments, without subsequent toxicological assessment, a large proportion of nontoxic sediments would be unnecessarily subjected to treatment and containment, and a number of sublethally toxic sediments would be missed. Even the best tiered systems that collect and evaluate information sequentially resulted in the failure to catch at least some sublethally or acutely toxic sediments. None of the AL2s examined were particularly effective in distinguishing between non-, sublethally, or acutely toxic sediments. Thus, this review did not support the use of chemical AL2s to predict the degree to which sediments will be toxic. Integr Environ Assess Manag 2017;13:1086-1099.© 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).

Evaluation of the Tobacco Heating System 2.2. Part 7: Systems toxicological assessment of a mentholated version revealed reduced cellular and molecular exposure effects compared with mentholated and non-mentholated cigarette smoke.

PubMed

Kogel, Ulrike; Titz, Bjoern; Schlage, Walter K; Nury, Catherine; Martin, Florian; Oviedo, Alberto; Lebrun, Stefan; Elamin, Ashraf; Guedj, Emmanuel; Trivedi, Keyur; Ivanov, Nikolai V; Vanscheeuwijck, Patrick; Peitsch, Manuel C; Hoeng, Julia

2016-11-30

Modified risk tobacco products (MRTPs) are being developed with the aim of reducing smoking-related health risks. The Tobacco Heating System 2.2 (THS2.2) is a candidate MRTP that uses the heat-not-burn principle. Here, systems toxicology approaches were engaged to assess the respiratory effects of mentholated THS2.2 (THS2.2M) in a 90-day rat inhalation study (OECD test guideline 413). The standard endpoints were complemented by transcriptomics and quantitative proteomics analyses of respiratory nasal epithelium and lung tissue and by lipidomics analysis of lung tissue. The adaptive response of the respiratory nasal epithelium to conventional cigarette smoke (CS) included squamous cell metaplasia and an inflammatory response, with high correspondence between the molecular and histopathological results. In contrast to CS exposure, the adaptive tissue and molecular changes to THS2.2M aerosol exposure were much weaker and were limited mostly to the highest THS2.2M concentration in female rats. In the lung, CS exposure induced an inflammatory response, triggered cellular stress responses, and affected sphingolipid metabolism. These responses were not observed or were much lower after THS2.2M aerosol exposure. Overall, this system toxicology analysis complements and reconfirms the results from classical toxicological endpoints and further suggests potentially reduced health risks of THS2.2M. Copyright © 2016. Published by Elsevier Inc.

Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA (ACS Fall meeting)

EPA Science Inventory

Abstract: Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intent...

Comptox Chemistry Dashboard: Web-Based Data Integration Hub for Environmental Chemistry and Toxicology Data (ACS Fall meeting 4 of 12)

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrate advances in biology, chemistry, exposure and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and da...

Delivering an Informational Hub for Data at the National Center for Computational Toxicology (ACS Spring Meeting) 7 of 7

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

New developments in delivering public access to data from the National Center for Computational Toxicology at the EPA

EPA Science Inventory

Researchers at EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The goal of this researc...

The need for a paradigm shift in toxicology xx.

EPA Science Inventory

This manuscript briefly reviews the impact of the NAS report “Toxicity Testing in the 21st Century: A Vision and A Strategy” and it’s potential impact on the field of toxicology. ). This report provides a strategic and tactical framework for attaining the goals of deter...

IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (Etbe) ...

EPA Pesticide Factsheets

In September 2016, EPA released the draft IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) for public comment and discussion. The draft assessment was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Ethyl Tertiary Butyl Ether are posted on this site. EPA is undertaking an new health assessment for ethyl tertiary butyl ether (ETBE) for the Integrated Risk Information System (IRIS). The outcome of this project will be a Toxicological Review and IRIS Summary of ETBE that will be entered on the IRIS database. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment process, i.e., hazard identification and dose-response evaluation. IRIS assessments are used nationally and internationally in combination with specific situational exposure assessment infor

Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy.

PubMed

Masuda, Akane; Masuda, Miyabi; Kawano, Takuya; Kitsunai, Yoko; Nakayama, Haruka; Nakajima, Hiroyuki; Kojima, Hiroyuki; Kitamura, Shigeyuki; Uramaru, Naoto; Hosaka, Takuomi; Sasaki, Takamitsu; Yoshinari, Kouichi

2017-01-01

Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.

Space Toxicology: Human Health during Space Operations

NASA Technical Reports Server (NTRS)

Khan-Mayberry, Noreen; James, John T.; Tyl, ROchelle; Lam, Chiu-Wing

2010-01-01

Space Toxicology is a unique and targeted discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion. As we begin to explore other celestial bodies in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

Techniques for Investigating Molecular Toxicology of Nanomaterials.

PubMed

Wang, Yanli; Li, Chenchen; Yao, Chenjie; Ding, Lin; Lei, Zhendong; Wu, Minghong

2016-06-01

Nanotechnology has been a rapidly developing field in the past few decades, resulting in the more and more exposure of nanomaterials to human. The increased applications of nanomaterials for industrial, commercial and life purposes, such as fillers, catalysts, semiconductors, paints, cosmetic additives and drug carriers, have caused both obvious and potential impacts on human health and environment. Nanotoxicology is used to study the safety of nanomaterials and has grown at the historic moment. Molecular toxicology is a new subdiscipline to study the interactions and impacts of materials at the molecular level. To better understand the relationship between the molecular toxicology and nanomaterials, this review summarizes the typical techniques and methods in molecular toxicology which are applied when investigating the toxicology of nanomaterials and include six categories: namely; genetic mutation detection, gene expression analysis, DNA damage detection, chromosomal aberration analysis, proteomics, and metabolomics. Each category involves several experimental techniques and methods.

CARDIOPATHIC EFFECT OF 1,2,3-TRICHLOROPROPANE AFTER SUBACUTE AND SUBCHRONIC EXPOSURE IN RATS

EPA Science Inventory

1,2,3-Trichloropropane (1,2,3-TCP) is an industrial water contaminant with potential for human exposure by the oral route. The systemic toxicology of 1,2,3-TCP was evaluated after subacute or subchronic exposure in male and female Sprague Dawley rate. Animals were treated with 0....

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 1,1,1-TRICHLOROETHANE (PEER REVIEW PLAN)

EPA Science Inventory

EPA's assessment of the carcinogenic potential of 1,1,1-trichloroethane was entered into the IRIS database in 1988, and the assessment of noncancer effects following oral exposure was withdrawn from IRIS in 1991. The IRIS program prepared an update of the IRIS assessment for 1,1,...

Temporal changes in biological responses and uncertainty in assessing risks of endocrine-disrupting chemicals: Insights from intensive time-course studies with fish

EPA Science Inventory

Most toxicological testing focuses on defining concentration/dose-response relationships, with little consideration given to temporal aspects of the expression of chemical effects. Yet, both variablesdose and timeare critical to robust evaluations of potential risks. Over the p...

NON-NEOPLASTIC LESIONS: USE OF DATA FROM PRE- OR NON-NEOPLASTIC LESIONS THAT MAY INDICATE POTENTIAL FOR CARCINOGENESIS

EPA Science Inventory

The Toxicology and Microbiology Division of the US EPA, Health Effects Research Laboratory has initiated a research program to develop a matrix of short-term tests to distinguish carcinogens from non-carcinogens among genotoxic substances and to develop methods for predicting rel...

SYSTEMIC VASCULAR DISEASE IN MALE B6C3F1 MICE EXPOSED TO PARTICULATE MATTER BY INHALATION: STUDIES CONDUCTED BY THE NATIONAL TOXICOLOGY PROGRAM

EPA Science Inventory

Abstract

Epidemiological studies suggest an association between ambient particulate matter and cardiopulmonary diseases in humans. The mechanisms underlying these health effects are poorly understood. To better understand the potential relationship between particulate-ma...

Health effects of uranium: new research findings.

PubMed

Brugge, Doug; Buchner, Virginia

2011-01-01

Recent plans for a nuclear renaissance in both established and emerging economies have prompted increased interest in uranium mining. With the potential for more uranium mining worldwide and a growth in the literature on the toxicology and epidemiology of uranium and uranium mining, we found it timely to review the current state of knowledge. Here, we present a review of the health effects of uranium mining, with an emphasis on newer findings (2005-2011). Uranium mining can contaminate air, water, and soil. The chemical toxicity of the metal constitutes the primary environmental health hazard, with the radioactivity of uranium a secondary concern. The update of the toxicologic evidence on uranium adds to the established findings regarding nephrotoxicity, genotoxicity, and developmental defects. Additional novel toxicologic findings, including some at the molecular level, are now emerging that raise the biological plausibility of adverse effects on the brain, on reproduction, including estrogenic effects, on gene expression, and on uranium metabolism. Historically, most epidemiology on uranium mining has focused on mine workers and radon exposure. Although that situation is still overwhelmingly true, a smaller emerging literature has begun to form around environmental exposure in residential areas near uranium mining and processing facilities. We present and critique such studies. Clearly, more epidemiologic research is needed to contribute to causal inference. As much damage is irreversible, and possibly cumulative, present efforts must be vigorous to limit environmental uranium contamination and exposure.

The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal)--experimental assessment using a zebrafish embryo test.

PubMed

Madureira, Tânia Vieira; Cruzeiro, Catarina; Rocha, Maria João; Rocha, Eduardo

2011-09-01

Fish embryos are a particularly vulnerable stage of development, so they represent optimal targets for screening toxicological effects of waterborne xenobiotics. Herein, the toxicity potential of two mixtures of pharmaceuticals was evaluated using a zebrafish embryo test. One of the mixtures corresponds to an environmentally realistic scenario and both have carbamazepine, fenofibric acid, propranolol, trimethoprim and sulfamethoxazole. The results evidenced morphological alterations, such as spinal deformities and yolk-sac oedemas. Moreover, heart rates decreased after both mixture exposures, e.g., at 48hpf, highest mixture versus blank control (47.8±4.9 and 55.8±3.7 beats/30s, respectively). The tail lengths also diminished significantly from 3208±145μm in blank control to 3130±126μm in highest mixture. The toxicological effects were concentration dependent. Mortality, hatching rate and the number of spontaneous movements were not affected. However, the low levels of pharmaceuticals did interfere with the normal development of zebrafish, which indicates risks for wild organisms. Copyright © 2011 Elsevier B.V. All rights reserved.

High risk of respiratory diseases in children in the fire period in Western Amazon

PubMed Central

Silva, Pãmela Rodrigues de Souza; Ignotti, Eliane; de Oliveira, Beatriz Fátima Alves; Junger, Washington Leite; Morais, Fernando; Artaxo, Paulo; Hacon, Sandra

2016-01-01

ABSTRACT OBJECTIVE To analyze the toxicological risk of exposure to ozone (O3) and fine particulate matter (PM2.5) among schoolchildren.. METHODS Toxicological risk assessment was used to evaluate the risk of exposure to O3 and PM2.5 from biomass burning among schoolchildren aged six to 14 years, residents of Rio Branco, Acre, Southern Amazon, Brazil. We used Monte Carlo simulation to estimate the potential intake dose of both pollutants. RESULTS During the slash-and-burn periods, O3 and PM2.5 concentrations reached 119.4 µg/m3 and 51.1 µg/m3, respectively. The schoolchildren incorporated medium potential doses regarding exposure to O3 (2.83 μg/kg.day, 95%CI 2.72–2.94). For exposure to PM2.5, we did not find toxicological risk (0.93 μg/kg.day, 95%CI 0.86–0.99). The toxicological risk for exposure to O3 was greater than 1 for all children (QR = 2.75; 95%CI 2.64–2.86). CONCLUSIONS Schoolchildren were exposed to high doses of O3 during the dry season of the region. This posed a toxicological risk, especially to those who had previous diseases. PMID:27305405

Blood transcriptomics: applications in toxicology

PubMed Central

Joseph, Pius; Umbright, Christina; Sellamuthu, Rajendran

2015-01-01

The number of new chemicals that are being synthesized each year has been steadily increasing. While chemicals are of immense benefit to mankind, many of them have a significant negative impact, primarily owing to their inherent chemistry and toxicity, on the environment as well as human health. In addition to chemical exposures, human exposures to numerous non-chemical toxic agents take place in the environment and workplace. Given that human exposure to toxic agents is often unavoidable and many of these agents are found to have detrimental human health effects, it is important to develop strategies to prevent the adverse health effects associated with toxic exposures. Early detection of adverse health effects as well as a clear understanding of the mechanisms, especially at the molecular level, underlying these effects are key elements in preventing the adverse health effects associated with human exposure to toxic agents. Recent developments in genomics, especially transcriptomics, have prompted investigations into this important area of toxicology. Previous studies conducted in our laboratory and elsewhere have demonstrated the potential application of blood gene expression profiling as a sensitive, mechanistically relevant and practical surrogate approach for the early detection of adverse health effects associated with exposure to toxic agents. The advantages of blood gene expression profiling as a surrogate approach to detect early target organ toxicity and the molecular mechanisms underlying the toxicity are illustrated and discussed using recent studies on hepatotoxicity and pulmonary toxicity. Furthermore, the important challenges this emerging field in toxicology faces are presented in this review article. PMID:23456664

Potential carcinogenic hazards of non-regulated disinfection by-products: haloquinones, halo-cyclopentene and cyclohexene derivatives, N-halamines, halonitriles, and heterocyclic amines.

PubMed

Bull, Richard J; Reckhow, David A; Li, Xingfang; Humpage, Andrew R; Joll, Cynthia; Hrudey, Steve E

2011-08-15

Drinking water disinfectants react with natural organic material (NOM) present in source waters used for drinking water to produce a wide variety of by-products. Several hundred disinfections by-products (DBPs) have been identified, but none have been identified with sufficient carcinogenic potency to account for the cancer risks projected from epidemiological studies. In a search for DBPs that might fill this risk gap, the present study projected reactions of chlorine and chloramine that could occur with substructures present in NOM to produce novel by-products. A review of toxicological data on related compounds, supplemented by use of a quantitative structure toxicity relationship (QSTR) program TOPKAT®) identified chemicals with a high probability of being chronically toxic and/or carcinogenic among 489 established and novel DBPs. Classes of DBPs that were specifically examined were haloquinones (HQs), related halo-cyclopentene and cyclohexene (HCP&H) derivatives, halonitriles (HNs), organic N-chloramines (NCls), haloacetamides (HAMs), and nitrosamines (NAs). A review of toxicological data available for quinones suggested that HQs and HCP&H derivatives appeared likely to be of health concern and were predicted to have chronic lowest observed adverse effect levels (LOAELs) in the low μg/kg day range. Several HQs were predicted to be carcinogenic. Some have now been identified in drinking water. The broader class of HNs was explored by considering current toxicological data on haloacetonitriles and extending this to halopropionitriles. 2,2-dichloropropionitrile has been identified in drinking water at low concentrations, as well as the more widely recognized haloacetonitriles. The occurrence of HAMs has been previously documented. The very limited toxicological data on HAMs suggests that this class would have toxicological potencies similar to the dihaloacetic acids. Organic N-halamines are also known to be produced in drinking water treatment and have biological properties of concern, but no member has ever been characterized toxicologically beyond bacterial or in vitro studies of genotoxicity. The documented formation of several nitrosamines from secondary amines from both natural and industrial sources prompted exploration of the formation of additional nitrosamines. N-diphenylnitrosamine was identified in drinking waters. Of more interest, however, was the formation of phenazine (and subsequently N-chorophenazine) in a competing reaction. These are the first heterocyclic amines that have been identified as chlorination by-products. Consideration of the amounts detected of members of these by-product classes and their probable toxicological potency suggest a prioritization for obtaining more detailed toxicological data of HQs>HCP&H derivatives>NCls>HNs. Based upon a ubiquitous occurrence and virtual lack of in vivo toxicological data, NCls are the most difficult group to assign a priority as potential carcinogenic risks. This analysis indicates that research on the general problem of DBPs requires a more systematic approach than has been pursued in the past. Utilization of predictive chemical tools to guide further research can help bring resolution to the DBP issue by identifying likely DBPs with high toxicological potency. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

Adverse Biological Effect of TiO2 and Hydroxyapatite Nanoparticles Used in Bone Repair and Replacement

PubMed Central

Wang, Jiangxue; Wang, Liting; Fan, Yubo

2016-01-01

The adverse biological effect of nanoparticles is an unavoidable scientific problem because of their small size and high surface activity. In this review, we focus on nano-hydroxyapatite and TiO2 nanoparticles (NPs) to clarify the potential systemic toxicological effect and cytotoxic response of wear nanoparticles because they are attractive materials for bone implants and are widely investigated to promote the repair and reconstruction of bone. The wear nanoparticles would be prone to binding with proteins to form protein-particle complexes, to interacting with visible components in the blood including erythrocytes, leukocytes, and platelets, and to being phagocytosed by macrophages or fibroblasts to deposit in the local tissue, leading to the formation of fibrous local pseudocapsules. These particles would also be translocated to and disseminated into the main organs such as the lung, liver and spleen via blood circulation. The inflammatory response, oxidative stress, and signaling pathway are elaborated to analyze the potential toxicological mechanism. Inhibition of the oxidative stress response and signaling transduction may be a new therapeutic strategy for wear debris–mediated osteolysis. Developing biomimetic materials with better biocompatibility is our goal for orthopedic implants. PMID:27231896

Newspaper reports from the Coroners Court in Ireland are used to reveal the potential complexity and need for reform in forensic toxicology and medicine services.

PubMed

Tormey, William P

2015-05-01

Newspapers devote regular space to inquests in the public interest. Accuracy in determining the causes of death is important for public health. Expert opinion features prominently in press reports and is an important channel of public education. How expert are the experts and how complex are apparently simple cases? Toxicology cases involving cannabis and stroke, 'junk food' diet, unexplained sudden death, potential drug interactions, allergy during caesarean section, and ecstacy-type drugs are used to illustrate the complexities. A template for reform is suggested to reform the Coroners Laws in Ireland to recognise the complexity of forensic toxicology and medicine. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Systematic approaches to toxicology in the zebrafish.

PubMed

Peterson, Randall T; Macrae, Calum A

2012-01-01

As the current paradigms of drug discovery evolve, it has become clear that a more comprehensive understanding of the interactions between small molecules and organismal biology will be vital. The zebrafish is emerging as a complement to existing in vitro technologies and established preclinical in vivo models that can be scaled for high-throughput. In this review, we highlight the current status of zebrafish toxicology studies, identify potential future niches for the model in the drug development pipeline, and define the hurdles that must be overcome as zebrafish technologies are refined for systematic toxicology.

Systems toxicology identifies mechanistic impacts of 2-amino-4,6-dinitrotoluene (2A-DNT) exposure in Northern Bobwhite.

PubMed

Gust, Kurt A; Nanduri, Bindu; Rawat, Arun; Wilbanks, Mitchell S; Ang, Choo Yaw; Johnson, David R; Pendarvis, Ken; Chen, Xianfeng; Quinn, Michael J; Johnson, Mark S; Burgess, Shane C; Perkins, Edward J

2015-08-07

A systems toxicology investigation comparing and integrating transcriptomic and proteomic results was conducted to develop holistic effects characterizations for the wildlife bird model, Northern bobwhite (Colinus virginianus) dosed with the explosives degradation product 2-amino-4,6-dinitrotoluene (2A-DNT). A subchronic 60 d toxicology bioassay was leveraged where both sexes were dosed via daily gavage with 0, 3, 14, or 30 mg/kg-d 2A-DNT. Effects on global transcript expression were investigated in liver and kidney tissue using custom microarrays for C. virginianus in both sexes at all doses, while effects on proteome expression were investigated in liver for both sexes and kidney in males, at 30 mg/kg-d. As expected, transcript expression was not directly indicative of protein expression in response to 2A-DNT. However, a high degree of correspondence was observed among gene and protein expression when investigating higher-order functional responses including statistically enriched gene networks and canonical pathways, especially when connected to toxicological outcomes of 2A-DNT exposure. Analysis of networks statistically enriched for both transcripts and proteins demonstrated common responses including inhibition of programmed cell death and arrest of cell cycle in liver tissues at 2A-DNT doses that caused liver necrosis and death in females. Additionally, both transcript and protein expression in liver tissue was indicative of induced phase I and II xenobiotic metabolism potentially as a mechanism to detoxify and excrete 2A-DNT. Nuclear signaling assays, transcript expression and protein expression each implicated peroxisome proliferator-activated receptor (PPAR) nuclear signaling as a primary molecular target in the 2A-DNT exposure with significant downstream enrichment of PPAR-regulated pathways including lipid metabolic pathways and gluconeogenesis suggesting impaired bioenergetic potential. Although the differential expression of transcripts and proteins was largely unique, the consensus of functional pathways and gene networks enriched among transcriptomic and proteomic datasets provided the identification of many critical metabolic functions underlying 2A-DNT toxicity as well as impaired PPAR signaling, a key molecular initiating event known to be affected in di- and trinitrotoluene exposures.

Mapping Proteome-Wide Interactions of Reactive Chemicals Using Chemoproteomic Platforms

PubMed Central

Counihan, Jessica L.; Ford, Breanna; Nomura, Daniel K.

2015-01-01

A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms. PMID:26647369

The Benefits of Making Data from the EPA National Center for Computational Toxicology available for reuse (ACS Fall meeting 3 of 12)

EPA Science Inventory

Researchers at EPA’s National Center for Computational Toxicology (NCCT) integrate advances in biology, chemistry, exposure and computer science to help prioritize chemicals for further research based on potential human health risks. The goal of this research is to quickly evalua...

Refinement, Reduction, and Replacement of Animal Toxicity Tests by Computational Methods.

PubMed

Ford, Kevin A

2016-12-01

Widespread public and scientific interest in promoting the care and well-being of animals used for toxicity testing has given rise to improvements in animal welfare practices and views over time, as well as laws and regulations that support means to reduce, refine, and replace animal use (known as the 3Rs) in certain toxicity studies. One way these regulations continue to achieve their aim is by promoting the research, development, and application of alternative testing approaches to characterize potential toxicities either without animals or with minimal use. An important example of an alternative approach is the use of computational toxicology models. Along with the potential capacity to reduce or replace the use of animals for the assessment of particular toxicological endpoints, computational models offer several advantages compared to in vitro and in vivo approaches, including cost-effectiveness, rapid availability of results, and the ability to fully standardize procedures. Pharmaceutical research incorporating the use of computational models has increased steadily over the past 15 years, likely driven by the motivation of companies to screen out toxic compounds in the early stages of development. Models are currently available to aid in the prediction of several important toxicological endpoints, including mutagenicity, carcinogenicity, eye irritation, hepatotoxicity, and skin sensitization, albeit with varying degrees of success. This review serves to introduce the concepts of computational toxicology and evaluate their role in the safety assessment of compounds, while also highlighting the application of in silico methods in the support of the goal and vision of the 3Rs. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research.All rights reserved. For permissions, please email: journals.permissions@oup.com.

Toxicology of hydrogen fluoride in relation to major accident hazards.

PubMed

Meldrum, M

1999-10-01

A major industrial accident involving the release of hydrogen fluoride has the potential to cause serious injury and possibly death in the surrounding human population. Given the potential for such serious and large-scale effects, there is a need for scientifically based risk assessments for determining appropriate on-site risk control measures, as well as for informing off-site emergency plans and land-use development decisions. Within Great Britain, the Health and Safety Executive (HSE) has the statutory responsibility for providing land-use planning advice in the vicinity of major accident hazard sites. The advice is based on quantified assessment of the individual risk of exposure to a specified amount of the toxic substance. Among other things this requires a consistent, reliable, and transparent understanding of the major hazard toxicology of the substance concerned. An assessment of the toxicology of hydrogen fluoride in relation to major accident hazards, based on conventional inhalation toxicity studies, was published by HSE in 1993. Recently, studies have been reported in which rats inhaled hydrogen fluoride via a mouthpiece attached to an endotracheal cannula. HSE has explored the use of this "mouth-breathing" rat model as a possible basis for human health risk assessment for hydrogen fluoride in the context of major accident hazards. A number of uncertainties in the use of this animal model have been identified that warrant caution in the use of this model for regulatory purposes. Overall, the results from the "mouth-breathing" rat model did not lead to a change in the HSE assessment of hydrogen fluoride, which remains based on experimental data obtained following "mainstream" toxicological practices. Copyright 1999 Academic Press.

In silico toxicology for the pharmaceutical sciences

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

Valerio, Luis G., E-mail: Luis.Valerio@fda.hhs.go

2009-12-15

The applied use of in silico technologies (a.k.a. computational toxicology, in silico toxicology, computer-assisted tox, e-tox, i-drug discovery, predictive ADME, etc.) for predicting preclinical toxicological endpoints, clinical adverse effects, and metabolism of pharmaceutical substances has become of high interest to the scientific community and the public. The increased accessibility of these technologies for scientists and recent regulations permitting their use for chemical risk assessment supports this notion. The scientific community is interested in the appropriate use of such technologies as a tool to enhance product development and safety of pharmaceuticals and other xenobiotics, while ensuring the reliability and accuracy ofmore » in silico approaches for the toxicological and pharmacological sciences. For pharmaceutical substances, this means active and impurity chemicals in the drug product may be screened using specialized software and databases designed to cover these substances through a chemical structure-based screening process and algorithm specific to a given software program. A major goal for use of these software programs is to enable industry scientists not only to enhance the discovery process but also to ensure the judicious use of in silico tools to support risk assessments of drug-induced toxicities and in safety evaluations. However, a great amount of applied research is still needed, and there are many limitations with these approaches which are described in this review. Currently, there is a wide range of endpoints available from predictive quantitative structure-activity relationship models driven by many different computational software programs and data sources, and this is only expected to grow. For example, there are models based on non-proprietary and/or proprietary information specific to assessing potential rodent carcinogenicity, in silico screens for ICH genetic toxicity assays, reproductive and developmental toxicity, theoretical prediction of human drug metabolism, mechanisms of action for pharmaceuticals, and newer models for predicting human adverse effects. How accurate are these approaches is both a statistical issue and challenge in toxicology. In this review, fundamental concepts and the current capabilities and limitations of this technology will be critically addressed.« less

IRIS Toxicological Review and Summary Documents for Chloroethane (Peer Review Plan)

EPA Science Inventory

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

Global change impact on oxidative potential and toxicity of atmospheric particles from the East Mediterranean basin: the ARCHIMEDES initiative

NASA Astrophysics Data System (ADS)

Alleman, Laurent; Anthérieu, Sébastien; Baeza-Squiban, Armelle; Garçon, Guillaume; Lo Guidice, Jean-Marc; Hamonou, Eric; Öztürk, Fatma; Perdrix, Esperanza; Rudich, Yinon; Sciare, Jean; Sauvage, Stéphane

2017-04-01

Climate change (CC) has important social, economical and health implications, notably in accordance with variation in air pollution or microbiome modification and its related toxicity mechanisms. CC will have a strong influence on meteorology, inducing dryer and warmer conditions in some regions. The Mediterranean basin is foreseen as a hotspot for regional climate warming, favoring larger dust episodes, wild fire events, vegetation emissions and changes in air pollution physic-chemical characteristics due to enhanced photochemical reactivity. Increasing concentrations of biogenic volatile organic compounds (VOCs), ozone, and radicals will be associated with rising concentrations of secondary organic aerosols (SOA) and other oxidized aerosols. These expected changes in aerosol composition are currently studied within the international ChArMEx (Chemistry-aerosol Mediterranean Experiment) program, part of the interdisciplinary MISTRALS metaprogramme (Mediterranean Integrated STudies at Regional And Local Scales). According to the LIFE/MED-PARTICLES (LIFE) project, this might result in more adverse effects on health. However, toxicologists are far from having a detailed mechanistic knowledge of the quantitative causal relations between particles (PM) and health effects suggested by epidemiological evidences. Detailed toxicological studies looking at contrasted PM origins and chemical compositions are highly needed, particularly on strongly aged SOA suspected to increase the oxidative potential (OP) and to enhance the toxicity of airborne particles. Intensive researches onto the underlying mechanisms of inflammation started to describe the outlines of the intricate relationship between oxidative stress and inflammation. It is therefore, of great importance to better determine the OP of PM from contrasted surroundings, its relationship with CC through PM's physical, chemical and microbial characteristics, and its toxicological consequences within the lungs. Recently, several projects under the ARCHIMEDES (Envi-MED funded) initiative including various research groups from Eastern Mediterranean countries have been submitted to French research calls. Their objectives are to develop an integrated testing strategy (ITS) through a combination of high throughput screening (HTS) methods based on acellular and lung cellular systems evaluating the respective OP (DTT, ascorbic acid and GSH depletion, DCFH oxidation) of various PM samples according to their origins in terms of sources and CC forecast. In order to ensure significant variability in ageing of the size segregated PM (fine, coarse) tested, samples from both northern (France) and southern countries (Cyprus, Israel, Turkey) should be collected at different seasons and site typologies, searching for various compositions and mixing states in SOA (biogenic, anthropogenic), metals and PAHs. These projects will combine relevant chemical, microbiological (DNA extract) and toxicological experiments (transcriptome, epigenome and secretome). A joint toxicological analysis related to their harmful effects on relevant oxidative (ATP, TAS, GSH/GSSG, gammaH2AX), inflammatory, genetic, and epigenetic endpoints within novel tissue-engineering tools will help in recapturing the native lung environment ex vivo. In the CC context, such projects will help to (1) better understand the cellular and molecular mechanisms of PM toxicity, (2) detect and predict their respiratory effects, (3) better comprehend the relationship between the physicochemical characteristics and the toxicological effects of PM, (4) provide innovative biomarkers that could be subsequently validated in humans and thereby contribute to the predictive toxicology.

Toxicologic evaluation of analytes from Tank 241-C-103

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

Mahlum, D.D.; Young, J.Y.; Weller, R.E.

1994-11-01

Westinghouse Hanford Company requested PNL to assemble a toxicology review panel (TRP) to evaluate analytical data compiled by WHC, and provide advice concerning potential health effects associated with exposure to tank-vapor constituents. The team`s objectives would be to (1) review procedures used for sampling vapors from tanks, (2) identify constituents in tank-vapor samples that could be related to symptoms reported by workers, (3) evaluate the toxicological implications of those constituents by comparison to establish toxicological databases, (4) provide advice for additional analytical efforts, and (5) support other activities as requested by WHC. The TRP represents a wide range of expertise,more » including toxicology, industrial hygiene, and occupational medicine. The TRP prepared a list of target analytes that chemists at the Oregon Graduate Institute/Sandia (OGI), Oak Ridge National Laboratory (ORNL), and PNL used to establish validated methods for quantitative analysis of head-space vapors from Tank 241-C-103. this list was used by the analytical laboratories to develop appropriate analytical methods for samples from Tank 241-C-103. Target compounds on the list included acetone, acetonitrile, ammonia, benzene, 1, 3-butadiene, butanal, n-butanol, hexane, 2-hexanone, methylene chloride, nitric oxide, nitrogen dioxide, nitrous oxide, dodecane, tridecane, propane nitrile, sulfur oxide, tributyl phosphate, and vinylidene chloride. The TRP considered constituent concentrations, current exposure limits, reliability of data relative to toxicity, consistency of the analytical data, and whether the material was carcinogenic or teratogenic. A final consideration in the analyte selection process was to include representative chemicals for each class of compounds found.« less

The toxic effects of calories

USDA-ARS?s Scientific Manuscript database

This is a new chapter in the Graduate School textbook "Cassarett & Doull's Toxicology". It is intended as a teaching text for graduate students in toxicology departments and programs and for the examination for professional certification as a Diplomate of the American Board of Toxicology (D.A.B.T.)...

Toxicological assessment of silica-coated iron oxide nanoparticles in human astrocytes.

PubMed

Fernández-Bertólez, Natalia; Costa, Carla; Brandão, Fátima; Kiliç, Gözde; Duarte, José Alberto; Teixeira, Joao Paulo; Pásaro, Eduardo; Valdiglesias, Vanessa; Laffon, Blanca

2018-04-27

Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and biological applications, particularly those focused on nervous system. Although ION seem to be biocompatible and present low toxicity, it is imperative to unveil the potential risk for the nervous system associated to their exposure, especially because current data on ION effects on human nervous cells are scarce. Thus, in the present study potential toxicity associated with silica-coated ION (S-ION) exposure was evaluated on human A172 glioblastoma cells. To this aim, a complete toxicological screening testing several exposure times (3 and 24 h), nanoparticle concentrations (5-100 μg/ml), and culture media (complete and serum-free) was performed to firstly assess S-ION effects at different levels, including cytotoxicity - lactate dehydrogenase assay, analysis of cell cycle and cell death production - and genotoxicity - H2AX phosphorylation assessment, comet assay, micronucleus test and DNA repair competence assay. Results obtained showed that S-ION exhibit certain cytotoxicity, especially in serum-free medium, related to cell cycle disruption and cell death induction. However, scarce genotoxic effects and no alteration of the DNA repair process were observed. Results obtained in this work contribute to increase the knowledge on the impact of ION on the human nervous system cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report.

PubMed

Zeiger, Errol; Gollapudi, Bhaskar; Aardema, Marilyn J; Auerbach, Scott; Boverhof, Darrell; Custer, Laura; Dedon, Peter; Honma, Masamitsu; Ishida, Seiichi; Kasinski, Andrea L; Kim, James H; Manjanatha, Mugimane G; Marlowe, Jennifer; Pfuhler, Stefan; Pogribny, Igor; Slikker, William; Stankowski, Leon F; Tanir, Jennifer Y; Tice, Raymond; van Benthem, Jan; White, Paul; Witt, Kristine L; Thybaud, Véronique

2015-04-01

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided. © 2014 Wiley Periodicals, Inc.

Update on EPA’s ToxCast Program: Providing High Throughput Decision Support Tools for Chemical Risk Management

EPA Science Inventory

The field of toxicology is on the cusp of a major transformation in how the safety and hazard of chemicals are evaluated for potential effects on human health and the environment. Brought on by the recognition of the limitations of the current paradigm in terms of cost, time, and...

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.

Alarms about structural alerts.

PubMed

Alves, Vinicius; Muratov, Eugene; Capuzzi, Stephen; Politi, Regina; Low, Yen; Braga, Rodolpho; Zakharov, Alexey V; Sedykh, Alexander; Mokshyna, Elena; Farag, Sherif; Andrade, Carolina; Kuz'min, Victor; Fourches, Denis; Tropsha, Alexander

2016-08-21

Structural alerts are widely accepted in chemical toxicology and regulatory decision support as a simple and transparent means to flag potential chemical hazards or group compounds into categories for read-across. However, there has been a growing concern that alerts disproportionally flag too many chemicals as toxic, which questions their reliability as toxicity markers. Conversely, the rigorously developed and properly validated statistical QSAR models can accurately and reliably predict the toxicity of a chemical; however, their use in regulatory toxicology has been hampered by the lack of transparency and interpretability. We demonstrate that contrary to the common perception of QSAR models as "black boxes" they can be used to identify statistically significant chemical substructures (QSAR-based alerts) that influence toxicity. We show through several case studies, however, that the mere presence of structural alerts in a chemical, irrespective of the derivation method (expert-based or QSAR-based), should be perceived only as hypotheses of possible toxicological effect. We propose a new approach that synergistically integrates structural alerts and rigorously validated QSAR models for a more transparent and accurate safety assessment of new chemicals.

Using Pareto points for model identification in predictive toxicology

PubMed Central

2013-01-01

Predictive toxicology is concerned with the development of models that are able to predict the toxicity of chemicals. A reliable prediction of toxic effects of chemicals in living systems is highly desirable in cosmetics, drug design or food protection to speed up the process of chemical compound discovery while reducing the need for lab tests. There is an extensive literature associated with the best practice of model generation and data integration but management and automated identification of relevant models from available collections of models is still an open problem. Currently, the decision on which model should be used for a new chemical compound is left to users. This paper intends to initiate the discussion on automated model identification. We present an algorithm, based on Pareto optimality, which mines model collections and identifies a model that offers a reliable prediction for a new chemical compound. The performance of this new approach is verified for two endpoints: IGC50 and LogP. The results show a great potential for automated model identification methods in predictive toxicology. PMID:23517649

Environmental Deflection: The Impact of Toxicant Exposures on the Aging Epigenome.

PubMed

Kochmanski, Joseph; Montrose, Luke; Goodrich, Jaclyn M; Dolinoy, Dana C

2017-04-01

Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift. Supporting this idea, other new reports have shown clear environment- and toxicant-mediated shifts away from the baseline rates of age-related methylation and epigenetic drift within an organism, a process we now term "environmental deflection." By defining and delineating environmental deflection, this contemporary review aims to highlight the effects of specific toxicological factors on the rate of DNA methylation changes that occur over the life course. In an effort to inform future epigenetics-based toxicology studies, a field of research now classified as toxicoepigenetics, we provide clear definitions and examples of "epigenetic drift" and "age-related methylation," summarize the recent evidence for environmental deflection of the aging epigenome, and discuss the potential functional effects of environmental deflection. © 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.

IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR 2-HEXANONE

EPA Science Inventory

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

The current role of on-line extraction approaches in clinical and forensic toxicology.

PubMed

Mueller, Daniel M

2014-08-01

In today's clinical and forensic toxicological laboratories, automation is of interest because of its ability to optimize processes, to reduce manual workload and handling errors and to minimize exposition to potentially infectious samples. Extraction is usually the most time-consuming step; therefore, automation of this step is reasonable. Currently, from the field of clinical and forensic toxicology, methods using the following on-line extraction techniques have been published: on-line solid-phase extraction, turbulent flow chromatography, solid-phase microextraction, microextraction by packed sorbent, single-drop microextraction and on-line desorption of dried blood spots. Most of these published methods are either single-analyte or multicomponent procedures; methods intended for systematic toxicological analysis are relatively scarce. However, the use of on-line extraction will certainly increase in the near future.

Hazard assessment of hydraulic fracturing chemicals using an indexing method.

PubMed

Hu, Guangji; Liu, Tianyi; Hager, James; Hewage, Kasun; Sadiq, Rehan

2018-04-01

The rapid expansion of unconventional natural gas production has triggered considerable public concerns, particularly regarding environmental and human health (EHH) risks posed by various chemical additives used in hydraulic fracturing (HF) operations. There is a need to assess the potential EHH hazards of additives used in real-world HF operations. In this study, HF additive and fracturing fluid data was acquired, and EHH hazards were assessed using an indexing approach. The indexing system analyzed chemical toxicological data of different ingredients contained within additives and produced an aggregated EHH safety index for each additive, along with an indicator describing the completeness of the chemical toxicological data. The results show that commonly used additives are generally associated with medium-level EHH hazards. In each additive category, ingredients of high EHH concern were identified, and the high hazard designation was primarily attributed to ingredients' high aquatic toxicity and carcinogenic effects. Among all assessed additive categories, iron control agents were identified as the greatest EHH hazards. Lack of information, such as undisclosed ingredients and chemical toxicological data gaps, has resulted in different levels of assessment uncertainties. In particular, friction reducers show the highest data incompleteness with regards to EHH hazards. This study reveals the potential EHH hazards associated with chemicals used in current HF field operations and can provide decision makers with valuable information to facilitate sustainable and responsible unconventional gas production. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of the Food Matrix and Gastrointestinal Tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps.

PubMed

McClements, David Julian; DeLoid, Glen; Pyrgiotakis, Georgios; Shatkin, Jo Anne; Xiao, Hang; Demokritou, Philip

2016-07-01

Many foods contain appreciable levels of engineered nanomaterials (ENMs) (diameter < 100 nm) that may be either intentionally or unintentionally added. These ENMs vary considerably in their compositions, dimensions, morphologies, physicochemical properties, and biological responses. From a toxicological point of view, it is often convenient to classify ingested ENMs (iENMs) as being either inorganic (such as TiO 2 , SiO 2 , Fe 2 O 3 , or Ag) or organic (such as lipid, protein, or carbohydrate), since the former tend to be indigestible and the latter are generally digestible. At present there is a relatively poor understanding of how different types of iENMs behave within the human gastrointestinal tract (GIT), and how the food matrix and biopolymers transform their physico-chemical properties and influence their gastrointestinal fate. This lack of knowledge confounds an understanding of their potential harmful effects on human health. The purpose of this article is to review our current understanding of the GIT fate of iENMs, and to highlight gaps where further research is urgently needed in assessing potential risks and toxicological implications of iENMs. In particular, a strong emphasis is given to the development of standardized screening methods that can be used to rapidly and accurately assess the toxicological properties of iENMs.

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.

Toxicological Implications and Inflammatory Response in Human Lymphocytes Challenged with Oxytetracycline.

PubMed

Di Cerbo, A; Palatucci, A T; Rubino, V; Centenaro, S; Giovazzino, A; Fraccaroli, E; Cortese, L; Ruggiero, G; Guidetti, G; Canello, S; Terrazzano, G

2016-04-01

Antibiotics are widely used in zoo technical and veterinary practices as feed supplementation to ensure wellness of farmed animals and livestock. Several evidences have been suggesting both the toxic role for tetracyclines, particularly for oxytetracycline (OTC). This potential toxicity appears of great relevance for human nutrition and for domestic animals. This study aimed to extend the evaluation of such toxicity. The biologic impact of the drug was assessed by evaluating the proinflammatory effect of OTC and their bone residues on cytokine secretion by in vitro human peripheral blood lymphocytes. Our results showed that both OTC and OTC-bone residues significantly induced the T lymphocyte and non-T cell secretion of interferon (IFN)-γ, as cytokine involved in inflammatory responses in humans as well as in animals. These results may suggest a possible implication for new potential human and animal health risks depending on the entry of tetracyclines in the food-processing chain. © 2015 The Authors Journal of Biochemical and Molecular Toxicology Published Wiley Periodicals, Inc.

GENOMIC ADAPTATION OF THE EMBRYONIC STEM CELL TEST (EST) FOR A TOXICOLOGICAL STUDY OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

Among the many promised and potential applications of embryonic stem cells, in vitro toxicology is one area in which ES cells have already proven their utility. In 2003, the Embryonic Stem Cell Test (EST) protocol was validated in Europe as an in vitro alternative to live animal...

Rubber (Hevea brasiliensis) seed oil toxicity effect and Linamarin compound analysis.

PubMed

Salimon, Jumat; Abdullah, Bashar Mudhaffar; Salih, Nadia

2012-06-13

The lipid fraction of rubber (Hevea brasiliensis (kunth. Muell)) seed was extracted and analyzed for toxicological effect. The toxicological compound such as linamarin in rubber seed oil (RSO) extracted using different solvents, such as hexane (RSOh), mixture of chloroform + methanol (RSOchl+mth) and ethanol (RSOeth) were also studied. Various methods analysis such as Fourier transforms infrared spectroscopy (FTIR) and colorimetric methods were carried out to determine the present of such compounds. FTIR spectrum of RSO did not show any presence of cyanide peak. The determination of cyanide by using colorimetric method was demonstrated no response of the cyanide in RSO and didn't show any colored comparing with commercial cyanide which observed blue color. The results showed that no functional groups such as cyanide (C ≡ N) associated with linamarin were observed. Toxicological test using rats was also conducted to further confirm the absence of such compounds. RSO did not show any toxic potential to the rats. Bioassay experiments using shrimps had been used as test organisms to evaluate the toxicity of linamarin extract from RSO(h,) RSO(chl+mth) and RSO(eth) and LC50 were found to be (211.70 %, 139.40 %, and 117.41 %, respectively). This can be attributed no hazardous linamarin were found in RSO.

IRIS Toxicological Review and Summary Documents for ...

EPA Pesticide Factsheets

Carbon tetrachloride is a volatile haloalkane with a wide range of industrial and chemical applications. It is produced commercially from chlorination of a variety of low molecular weight hydrocarbons such as carbon disulfide, methanol, methane, propane, and ethylene dichloride. It is also produced by thermal chlorination in the production of tetrachloroethylene. Major uses of carbon tetrachloride have been in the recovery of tin from tin plating waste, in formulation of petrol additives and refrigerants, in metal degreasing and agricultural fumigants, in chlorination of organic compounds, in the production of semiconductors, in the reduction of fire hazard, as a solvent for rubber cement, and as a catalyst in polymer technology. Its production has been decreasing and it is no longer permitted in products intended for home use. Despite this ban, carbon tetrachloride has been detected at 314 hazardous waste sites. EPA's assessment of noncancer health effects and carcinogenic potential of carbon tetrachloride was last prepared and added to the IRIS database in 1991. The IRIS program is preparing an assessment that will incorporate health effects information available for carbon tetrachloride, and current risk assessment methods. The IRIS assessment for carbon tetrachloride will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity

Rubber (Hevea brasiliensis) seed oil toxicity effect and Linamarin compound analysis

PubMed Central

2012-01-01

Background The lipid fraction of rubber (Hevea brasiliensis (kunth. Muell)) seed was extracted and analyzed for toxicological effect. The toxicological compound such as linamarin in rubber seed oil (RSO) extracted using different solvents, such as hexane (RSOh), mixture of chloroform + methanol (RSOchl+mth) and ethanol (RSOeth) were also studied. Various methods analysis such as Fourier transforms infrared spectroscopy (FTIR) and colorimetric methods were carried out to determine the present of such compounds. Results FTIR spectrum of RSO did not show any presence of cyanide peak. The determination of cyanide by using colorimetric method was demonstrated no response of the cyanide in RSO and didn’t show any colored comparing with commercial cyanide which observed blue color. The results showed that no functional groups such as cyanide (C ≡ N) associated with linamarin were observed. Toxicological test using rats was also conducted to further confirm the absence of such compounds. RSO did not show any toxic potential to the rats. Bioassay experiments using shrimps had been used as test organisms to evaluate the toxicity of linamarin extract from RSOh, RSOchl+mth and RSOeth and LC50 were found to be (211.70 %, 139.40 %, and 117.41 %, respectively). Conclusions This can be attributed no hazardous linamarin were found in RSO. PMID:22694753

Toxicology of organophosphorus compounds in view of an increasing terrorist threat.

PubMed

Worek, Franz; Wille, Timo; Koller, Marianne; Thiermann, Horst

2016-09-01

The implementation of the Chemical Weapon Convention (CWC), prohibiting the development, production, storage and use of chemical weapons by 192 nations and the ban of highly toxic OP pesticides, especially class I pesticides according to the WHO classification, by many countries constitutes a great success of the international community. However, the increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents new challenges to our societies. Almost seven decades of research on organophosphorus compound (OP) toxicology was mainly focused on a small number of OP nerve agents despite the fact that a huge number of OP analogues, many of these agents having comparable toxicity to classical nerve agents, were synthesized and published. Only limited physicochemical, toxicological and medical information on nerve agent analogues is available in the open literature. This implies potential gaps of our capabilities to detect, to decontaminate and to treat patients if nerve agent analogues are disseminated and may result in inadequate effectiveness of newly developed countermeasures. In summary, our societies may face new, up to now disregarded, threats by toxic OP which calls for increased awareness and appropriate preparedness of military and civilian CBRN defense, a broader approach for new physical and medical countermeasures and an integrated system of effective detection, decontamination, physical protection and treatment.

Toxicological effects of irregularly shaped and spherical microplastics in a marine teleost, the sheepshead minnow (Cyprinodon variegatus).

PubMed

Choi, Jin Soo; Jung, Youn-Joo; Hong, Nam-Hui; Hong, Sang Hee; Park, June-Woo

2018-04-01

The increasing global contamination of plastics in marine environments is raising public concerns about the potential hazards of microplastics to environmental and human health. Microplastics formed by the breakdown of larger plastics are typically irregular in shape. The objective of this study was to compare the effects of spherical or irregular shapes of microplastics on changes in organ distribution, swimming behaviors, gene expression, and enzyme activities in sheepshead minnow (Cyprinodon variegatus). Both types of microplastics accumulated in the digestive system, causing intestinal distention. However, when compared to spherical microplastics, irregular microplastics decreased swimming behavior (i.e., total distance travelled and maximum velocity) of sheepshead minnow. Both microplastics generated cellular reactive oxygen species (ROS), while ROS-related molecular changes (i.e., transcriptional and enzymatic characteristics) differed. This study provides toxicological insights into the impacts of environmentally relevant (fragmented) microplastics on fish and improves our understanding of the environmental effects of microplastics in the ecosystem. Copyright © 2018 Elsevier Ltd. All rights reserved.

Implications of gender differences for human health risk assessment and toxicology

EPA Science Inventory

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exp...

Toxicology: Old Art, New Science.

ERIC Educational Resources Information Center

Timbrell, John A.

1983-01-01

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

The safety of green tea and green tea extract consumption in adults - Results of a systematic review.

PubMed

Hu, Jiang; Webster, Donna; Cao, Joyce; Shao, Andrew

2018-06-01

A systematic review of published toxicology and human intervention studies was performed to characterize potential hazards associated with consumption of green tea and its preparations. A review of toxicological evidence from laboratory studies revealed the liver as the target organ and hepatotoxicity as the critical effect, which was strongly associated with certain dosing conditions (e.g. bolus dose via gavage, fasting), and positively correlated with total catechin and epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from 159 human intervention studies yielded findings consistent with toxicological evidence in that a limited range of concentrated, catechin-rich green tea preparations resulted in hepatic AEs in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed tea or extracts in beverages or as part of food. Toxico- and pharmacokinetic evidence further suggests internal dose of catechins is a key determinant in the occurrence and severity of hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived from toxicological and human safety data for tea preparations ingested as a solid bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered for tea preparations in beverage form based on human AE data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

Functional toxicogenomic assessment of triclosan in human ...

EPA Pesticide Factsheets

Thousands of chemicals for which limited toxicological data are available are used and then detected in humans and the environment. Rapid and cost-effective approaches for assessing the toxicological properties of chemicals are needed. We used CRISPR-Cas9 functional genomic screening to identify potential molecular mechanism of a widely used antimicrobial triclosan (TCS) in HepG2 cells. Resistant genes (whose knockout gives potential resistance) at IC50 (50% Inhibition concentration of cell viability) were significantly enriched in adherens junction pathway, MAPK signaling pathway and PPAR signaling pathway, suggesting a potential molecular mechanism in TCS induced cytotoxicity. Evaluation of top-ranked resistant genes, FTO (encoding an mRNA demethylase) and MAP2K3 (a MAP kinase kinase family gene), revealed that their loss conferred resistance to TCS. In contrast, sensitive genes (whose knockout enhances potential sensitivity) at IC10 and IC20 were specifically enriched in pathways involved with immune responses, which was concordant with the transcriptomic profiling of TCS at concentrations

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

Toxicodynetics: A new discipline in clinical toxicology.

PubMed

Baud, F J; Houzé, P; Villa, A; Borron, S W; Carli, P

2016-05-01

Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course of relevant toxic effects both in experimental and clinical studies. The lack of a discipline devoted to this major field in toxicology results in misconception and even in errors by clinicians. Review of the basic different disciplines that encompass pharmacology toxicology and comparing with the description of the time-course of effects in conditions in which toxicological analysis was not performed or with limited analytical evidence. Review of the literature clearly shows how misleading is the current extrapolation of toxicokinetic data to the description of the time-course of toxic effects. A new discipline entitled toxicodynetics should be developed aiming at a more systematic description of the time-course of effects in acute human and experimental poisonings. Toxicodynetics might help emergency physicians in risk assessment when facing a poisoning and contribute to a better assessment of quality control of data collected by poison control centres. Toxicodynetics would also allow a quantitative approach to the clinical effects resulting from drug-drug interaction. Copyright © 2016. Published by Elsevier Masson SAS.

Diagnostic yield of hair and urine toxicology testing in potential child abuse cases.

PubMed

Stauffer, Stephanie L; Wood, Stephanie M; Krasowski, Matthew D

2015-07-01

Detection of drugs in a child may be the first objective finding that can be reported in cases of suspected child abuse. Hair and urine toxicology testing, when performed as part of the initial clinical evaluation for suspected child abuse or maltreatment, may serve to facilitate the identification of at-risk children. Furthermore, significant environmental exposure to a drug (considered by law to constitute child abuse in some states) may be identified by toxicology testing of unwashed hair specimens. In order to determine the clinical utility of hair and urine toxicology testing in this population we performed a retrospective chart review on all children for whom hair toxicology testing was ordered at our academic medical center between January 2004 and April 2014. The medical records of 616 children aged 0-17.5 years were reviewed for injury history, previous medication and illicit drug use by caregiver(s), urine drug screen result (if performed), hair toxicology result, medication list, and outcome of any child abuse evaluation. Hair toxicology testing was positive for at least one compound in 106 cases (17.2%), with unexplained drugs in 82 cases (13.3%). Of these, there were 48 cases in which multiple compounds (including combination of parent drugs and/or metabolites within the same drug class) were identified in the sample of one patient. The compounds most frequently identified in the hair of our study population included cocaine, benzoylecgonine, native (unmetabolized) tetrahydrocannabinol, and methamphetamine. There were 68 instances in which a parent drug was identified in the hair without any of its potential metabolites, suggesting environmental exposure. Among the 82 cases in which hair toxicology testing was positive for unexplained drugs, a change in clinical outcome was noted in 71 cases (86.5%). Urine drug screens (UDS) were performed in 457 of the 616 reviewed cases. Of these, over 95% of positive UDS results could be explained by iatrogenic drug administration. There were no cases in which a urine drug screen alone altered the outcome of a case. In summary, hair toxicology testing proved clinically useful in the evaluation of a child for suspected abuse; in contrast, urine drug testing showed low clinical yield. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

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.

Live-cell Imaging Approaches for the Investigation of ...

EPA Pesticide Factsheets

BACKGROUND: Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes.SCOPE OF REVIEW: The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies.MAJOR CONCLUSIONS: Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress.GENERAL SIGNIFICANCE: Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenju

Toxicological Benchmarks for Screening Potential Contaminants of Concern for Effects on Soil and Litter Invertebrates and Heterotrophic Process

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

Will, M.E.

1994-01-01

This report presents a standard method for deriving benchmarks for the purpose of ''contaminant screening,'' performed by comparing measured ambient concentrations of chemicals. The work was performed under Work Breakdown Structure 1.4.12.2.3.04.07.02 (Activity Data Sheet 8304). In addition, this report presents sets of data concerning the effects of chemicals in soil on invertebrates and soil microbial processes, benchmarks for chemicals potentially associated with United States Department of Energy sites, and literature describing the experiments from which data were drawn for benchmark derivation.

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.

77 FR 38799 - Draft Toxicological Review of 1,2,3-, 1,2,4-, and 1,3,5-Trimethylbenzene: In Support of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... period and a public listening session for the external review draft human health assessment titled... body established under the Federal Advisory Committee Act with a broad mandate to advise the Agency on.... Information about IRIS IRIS is a database that contains potential adverse human health effects information...

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.

The potential effects of Ocimum basilicum on health: a review of pharmacological and toxicological studies.

PubMed

Sestili, Piero; Ismail, Tariq; Calcabrini, Cinzia; Guescini, Michele; Catanzaro, Elena; Turrini, Eleonora; Layla, Anam; Akhtar, Saeed; Fimognari, Carmela

2018-07-01

Basil (Ocimum basilicum L., OB) is a plant world widely used as a spice and a typical ingredient of the healthy Mediterranean diet. In traditional medicine, OB is indicated for many maladies and conditions; OB-containing nutritional supplements are increasingly sold. Conversely, safety concerns have been raised about the promutagens and procarcinogens alkenylbenzenes contained in OB. Areas covered: A critical review of the current status of OB as a nutraceutical, the pharmacology of its bioactive components, the rationale for its indications, and its safety. Expert opinion: Due to the polyphenolic and flavonoidic content, OB can be considered as an important ingredient in healthy diets; OB preparations may be effective as chemopreventive agents or adjunctive therapy in the treatment of different clinical conditions. From a toxicological perspective, since the tumorigenic potential of alkenylbenzenes is counteracted by other OB constituents such as nevadensin, it can be concluded that OB consumption in food and preparations is safe. The only concern relates to OB essential oils: in this case, a concentration limit for alkenylbenzenes should be precautionary defined, and the use of plant chemotypes with no or low levels of these alkylbenzenes for the preparation of essential oils should be made compulsory.

Toxicological evaluation of Euterpe edulis: a potential superfruit to be considered.

PubMed

Felzenszwalb, Israel; da Costa Marques, Monica Regina; Mazzei, José L; Aiub, Claudia A F

2013-08-01

Superfruits have a high nutritional value due to their richness in nutrients, antioxidants, proven or potential health benefits and taste appeal. However, there are no scientific criteria for defining which fruits are superfruits. In Brazil, several palms have an edible palm heart, the best known and most widely appreciated of which is called Acai (Euterpe oleracea). Euterpe edulis Mart., commonly called jussara, is an evergreen species that grows in the rainforest. Having initially been consumed in the form of juice and pulp, they have since been incorporated as an ingredient in many foods. A risk assessment to identify adverse health effects is a prerequisite for taking forward the development of new drugs, cosmetics and foods. To make a toxicological evaluation of E. edulis, in the present work this prerequisite was met by an interdisciplinary network that performed mass spectroscopy analyses, blood biochemistry, genotoxicity, bacterial reverse mutation and cytotoxicity assays. Positive mutagenicity results were detected for Salmonella typhimurium TA97 at low doses, and positive results were also obtained for the mammalian erythrocyte micronucleus assay, indicating that the pulp of E. edulis contains compounds with the capacity to induce mutagenicity and clastogenic/aneugenic effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Current toxicological aspects on drug and chemical transport and metabolism across the human placental barrier.

PubMed

Giaginis, Constantinos; Theocharis, Stamatios; Tsantili-Kakoulidou, Anna

2012-10-01

Placenta plays an obligatory role in fetal growth and development by performing a multitude of functions, including embryo implantation, transport of nutrients and elimination of metabolic waste products and endocrine activity. Drugs and chemicals can transfer across the placental barrier from mother to fetus either by passive diffusion mechanisms and/or via a network of active transporters, which may lead to potential fetotoxicity effects. Placenta also expresses a wide variety of enzymes, being capable of metabolizing a large diversity of drugs and chemicals to metabolites of lower or even higher toxicity than parent compounds. The present review aims to summarize the current toxicological aspects in the emerging topic of drug transport and metabolism across the human placental barrier. There is an emerging demand for accurate assessment of drug transport and metabolism across the human placental barrier, on the basis of a high throughput screening process in the early stages of drug design, to avoid drug candidates from potential fetotoxicity effects. In this aspect, combined studies, which take into account in vivo and in vitro investigations, as well as the ex vivo perfusion method and the recently developed computer-aided technologies, may significantly contribute to this direction.

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.

Pathophysiological Progression Model for Selected Toxicological Endpoints

EPA Science Inventory

The existing continuum paradigms are effective models to organize toxicological data associated with endpoints used in human health assessments. A compendium of endpoints characterized along a pathophysiological continuum would serve to: weigh the relative importance of effects o...

Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

PubMed

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

2016-09-10

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-precautionary aspects of toxicology

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

Grandjean, Philippe

2005-09-01

Empirical studies in toxicology aim at deciphering complex causal relationships, especially in regard to human disease etiologies. Several scientific traditions limit the usefulness of documentation from current toxicological research, in regard to decision-making based on the precautionary principle. Among non-precautionary aspects of toxicology are the focus on simplified model systems and the effects of single hazards, one by one. Thus, less attention is paid to sources of variability and uncertainty, including individual susceptibility, impacts of mixed and variable exposures, susceptible life-stages, and vulnerable communities. In emphasizing the need for confirmatory evidence, toxicology tends to penalize false positives more than falsemore » negatives. An important source of uncertainty is measurement error that results in misclassification, especially in regard to exposure assessment. Standard statistical analysis assumes that the exposure is measured without error, and imprecisions will usually result in an underestimation of the dose-effect relationship. In testing whether an effect could be considered a possible result of natural variability, a 5% limit for 'statistical significance' is usually applied, even though it may rule out many findings of causal associations, simply because the study was too small (and thus lacked statistical power) or because some imprecision or limited sensitivity of the parameters precluded a more definitive observation. These limitations may be aggravated when toxicology is influenced by vested interests. Because current toxicology overlooks the important goal of achieving a better characterization of uncertainties and their implications, research approaches should be revised and strengthened to counteract the innate ideological biases, thereby supporting our confidence in using toxicology as a main source of documentation and in using the precautionary principle as a decision procedure in the public policy arena.« less

Frequency of forensic toxicological analysis in external cause deaths among nursing home residents: an analysis of trends.

PubMed

Aitken, Georgia; Murphy, Briony; Pilgrim, Jennifer; Bugeja, Lyndal; Ranson, David; Ibrahim, Joseph Elias

2017-03-01

There is a paucity of research examining the utility of forensic toxicology in the investigation of premature external cause deaths of residents in nursing homes. The aim of this study is to describe the frequency and characteristics of toxicological analysis conducted in external cause (injury-related) deaths amongst nursing home residents in Victoria, Australia. This study was a retrospective cohort study examining external cause deaths among nursing home residents during the period July 1, 2000 to December 31, 2012 in Victoria, Australia, using the National Coronial Information System (NCIS). The variables examined comprised: sex, age group, year-of-death, cause and manner of death. One-third of deaths among nursing home residents in Victoria resulted from external causes (n = 1296, 33.3%) of which just over one-quarter (361, 27.9%) underwent toxicological analysis as part of the medical death investigation. The use of toxicological analysis varied by cause of death with a relatively low proportion conducted in deaths from unintentional falls (n = 286, 24.9%) and choking (n = 36, 40.4%). The use of toxicological analysis decreased as the decedents age increased. Forensic toxicology has the potential to contribute to improving our understanding of premature deaths in nursing home residents however it remains under used and is possibly undervalued.

Mephedrone: use, subjective effects and health risks.

PubMed

Winstock, Adam; Mitcheson, Luke; Ramsey, John; Davies, Susannah; Puchnarewicz, Malgorzata; Marsden, John

2011-11-01

To assess the patterns of use, subjective effect profile and dependence liability of mephedrone, supported by corroborative urine toxicology. Cross-sectional structured telephone interview. UK-based drug users associated with the dance music scene. A total of 100 mephedrone users, recruited through their involvement with the dance music scene. Assessment of pattern of use, acute and after effects, DSM dependence criteria and gas chromatography-mass spectrometry urinalysis. Mephedrone consumption results in typical stimulant-related subjective effects: euphoria, increased concentration, talkativeness, urge to move, empathy, jaw clenching, reduced appetite and insomnia. Thirty per cent of the sample potentially met criteria for DSM-IV dependence and there was evidence of a strong compulsion to use the drug (47% had used the drug for 2 or more consecutive days). Self-reported recent consumption of mephedrone was confirmed by toxicological analysis in all of the 14 participants who submitted a urine sample. Mephedrone has a high abuse and health risk liability, with increased tolerance, impaired control and a compulsion to use, the predominant reported dependence symptoms. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Metabolomics in Toxicology and Preclinical Research

PubMed Central

Ramirez, Tzutzuy; Daneshian, Mardas; Kamp, Hennicke; Bois, Frederic Y.; Clench, Malcolm R.; Coen, Muireann; Donley, Beth; Fischer, Steven M.; Ekman, Drew R.; Fabian, Eric; Guillou, Claude; Heuer, Joachim; Hogberg, Helena T.; Jungnickel, Harald; Keun, Hector C.; Krennrich, Gerhard; Krupp, Eckart; Luch, Andreas; Noor, Fozia; Peter, Erik; Riefke, Bjoern; Seymour, Mark; Skinner, Nigel; Smirnova, Lena; Verheij, Elwin; Wagner, Silvia; Hartung, Thomas; van Ravenzwaay, Bennard; Leist, Marcel

2013-01-01

Summary Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context. PMID:23665807

Meta-analysis of ionic liquid literature and toxicology.

PubMed

Heckenbach, Mary E; Romero, Felicia N; Green, Matthew D; Halden, Rolf U

2016-05-01

A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213) with the goal of establishing the state of knowledge and existing information gaps. Additionally, patent literature pertaining to issued patents utilizing ILs (n = 3358) or dealing with IL toxicity (n = 112) were analyzed. Total publishing activity and patent count served to gauge research activity, industrial usage and toxicology knowledge of ILs. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 0.55% ± 0.27% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemical. Toxicity studies on ILs were dominated by the use of in vitro models (18%) and marine bacteria (15%) as studied biological systems. Whole animal studies (n = 87) comprised 31% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need to fill crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Meta-Analysis of Ionic Liquid Literature and Toxicology

PubMed Central

Heckenbach, Mary E.; Romero, Felicia N.; Green, Matthew D.; Halden, Rolf U.

2016-01-01

A meta-analysis was conducted to compare the total amount of ionic liquid (IL) literature (n = 39,036) to the body of publications dealing with IL toxicity (n = 213) with the goal of establishing the state of knowledge and existing information gaps. Additionally, patent literature pertaining to issued patents utilizing ILs (n = 3,358) or dealing with IL toxicity (n =112) were analyzed. Total publishing activity and patent count served to gauge research activity, industrial usage and toxicology knowledge of ILs. Five of the most commonly studied IL cations were identified and used to establish a relationship between toxicity data and potential of commercial use: imidazolium, ammonium, phosphonium, pyridinium, and pyrrolidinium. Toxicology publications for all IL cations represented 0.55% ± 0.27% of the total publishing activity; compared with other industrial chemicals, these numbers indicate that there is still a paucity of studies on the adverse effects of this class of chemical. Toxicity studies on ILs were dominated by the use of in vitro models (18%) and marine bacteria (15%) as studied biological systems. Whole animal studies (n = 87) comprised 31% of IL toxicity studies, with a subset of in vivo mammalian models consisting of 8%. Human toxicology data were found to be limited to in vitro analyses, indicating substantial knowledge gaps. Risks from long-term and chronic low-level exposure to ILs have not been established yet for any model organisms, reemphasizing the need to fill crucial knowledge gaps concerning human health effects and the environmental safety of ILs. Adding to the existing knowledge of the molecular toxicity characteristics of ILs can help inform the design of greener, less toxic and more benign IL technologies. PMID:26907595

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

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

Prouillac, Caroline, E-mail: c.prouillac@vetagro-sup.fr; Koraichi, Farah; Videmann, Bernadette

2012-03-15

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

Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach.

PubMed

Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

2016-07-15

Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials.

Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach

PubMed Central

Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

2016-01-01

Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials. PMID:27417574

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

Computational Approaches to Chemical Hazard Assessment

PubMed Central

Luechtefeld, Thomas; Hartung, Thomas

2018-01-01

Summary Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information. Our earlier publications have characterized a toxicological dataset of unprecedented scale resulting from the European REACH legislation (Registration Evaluation Authorisation and Restriction of Chemicals). These publications dove into potential use cases for regulatory data and some models for exploiting this data. This article analyzes the options for the identification and categorization of chemicals, moves on to the derivation of descriptive features for chemicals, discusses different kinds of targets modeled in computational toxicology, and ends with a high-level perspective of the algorithms used to create computational toxicology models. PMID:29101769

Predictive Structure-Based Toxicology Approaches To Assess the Androgenic Potential of Chemicals.

PubMed

Trisciuzzi, Daniela; Alberga, Domenico; Mansouri, Kamel; Judson, Richard; Novellino, Ettore; Mangiatordi, Giuseppe Felice; Nicolotti, Orazio

2017-11-27

We present a practical and easy-to-run in silico workflow exploiting a structure-based strategy making use of docking simulations to derive highly predictive classification models of the androgenic potential of chemicals. Models were trained on a high-quality chemical collection comprising 1689 curated compounds made available within the CoMPARA consortium from the US Environmental Protection Agency and were integrated with a two-step applicability domain whose implementation had the effect of improving both the confidence in prediction and statistics by reducing the number of false negatives. Among the nine androgen receptor X-ray solved structures, the crystal 2PNU (entry code from the Protein Data Bank) was associated with the best performing structure-based classification model. Three validation sets comprising each 2590 compounds extracted by the DUD-E collection were used to challenge model performance and the effectiveness of Applicability Domain implementation. Next, the 2PNU model was applied to screen and prioritize two collections of chemicals. The first is a small pool of 12 representative androgenic compounds that were accurately classified based on outstanding rationale at the molecular level. The second is a large external blind set of 55450 chemicals with potential for human exposure. We show how the use of molecular docking provides highly interpretable models and can represent a real-life option as an alternative nontesting method for predictive toxicology.

Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern?

PubMed

Bredsdorff, Lea; Wedebye, Eva Bay; Nikolov, Nikolai Georgiev; Hallas-Møller, Torben; Pilegaard, Kirsten

2015-10-01

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 μg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Research Update: Electrical monitoring of cysts using organic electrochemical transistors a

NASA Astrophysics Data System (ADS)

Huerta, M.; Rivnay, J.; Ramuz, M.; Hama, A.; Owens, R. M.

2015-03-01

Organotypic three-dimensional (3D) cell culture models have the potential to act as surrogate tissues in vitro, both for basic research and for drug discovery/toxicology. 3D cultures maintain not only 3D architecture but also cell-cell and cell extracellular matrix interactions, particularly when grown in cysts or spheroids. Characterization of cell cultures grown in 3D formats, however, provides a significant challenge for cell biologists due to the incompatibility of these structures with commonly found optical or electronic monitoring systems. Electronic impedance spectroscopy is a cell culture monitoring technique with great potential; however, it has not been possible to integrate 3D cultures with commercially available systems to date. Cyst-like 3D cultures are particularly challenging due to their small size and difficulty in manipulation. Herein, we demonstrate isolation of cyst-like 3D cultures by capillarity and subsequent integration with the organic electrochemical transistor for monitoring the integrity of these structures. We show not only that this versatile device can be adapted to the cyst format for measuring resistance and, therefore, the quality of the cysts, but also can be used for quantitative monitoring of the effect of toxic compounds on cells in a 3D format. The ability to quantitatively predict effects of drugs on 3D cultures in vitro has large future potential for the fields of drug discovery and toxicology.

Research Update: Electrical monitoring of cysts using organic electrochemical transistors

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

Huerta, M.; Rivnay, J.; Ramuz, M.

2015-03-01

Organotypic three-dimensional (3D) cell culture models have the potential to act as surrogate tissues in vitro, both for basic research and for drug discovery/toxicology. 3D cultures maintain not only 3D architecture but also cell-cell and cell extracellular matrix interactions, particularly when grown in cysts or spheroids. Characterization of cell cultures grown in 3D formats, however, provides a significant challenge for cell biologists due to the incompatibility of these structures with commonly found optical or electronic monitoring systems. Electronic impedance spectroscopy is a cell culture monitoring technique with great potential; however, it has not been possible to integrate 3D cultures withmore » commercially available systems to date. Cyst-like 3D cultures are particularly challenging due to their small size and difficulty in manipulation. Herein, we demonstrate isolation of cyst-like 3D cultures by capillarity and subsequent integration with the organic electrochemical transistor for monitoring the integrity of these structures. We show not only that this versatile device can be adapted to the cyst format for measuring resistance and, therefore, the quality of the cysts, but also can be used for quantitative monitoring of the effect of toxic compounds on cells in a 3D format. The ability to quantitatively predict effects of drugs on 3D cultures in vitro has large future potential for the fields of drug discovery and toxicology.« less

Avian models for toxicity testing

USGS Publications Warehouse

Hill, E.F.; Hoffman, D.J.

1984-01-01

The use of birds as test models in experimental and environmental toxicology as related to health effects is reviewed, and an overview of descriptive tests routinely used in wildlife toxicology is provided. Toxicologic research on birds may be applicable to human health both directly by their use as models for mechanistic and descriptive studies and indirectly as monitors of environmental quality. Topics include the use of birds as models for study of teratogenesis and embryotoxicity, neurotoxicity, behavior, trends of environmental pollution, and for use in predictive wildlife toxicology. Uses of domestic and wild-captured birds are discussed.

4-methylamphetamine (4-MA): chemistry, pharmacology and toxicology of a new potential recreational drug.

PubMed

Coppola, M; Mondola, R

2013-12-01

From 2005 to 2012, 236 new substances have been officially notified in European Union via the Early Warning System with an increasing trend from year by year. In October 2009, 4-methylamphetamine (4-MA), an amphetamine derivative, was detected in Belgium and on 14 December 2009 this stimulant was notified to the European Monitoring Centre for Drugs and Drug Addiction. Since its appearance within the recreational drug market, some cases of severe intoxication and deaths have been signaled across Europe. In this paper we summarized the chemical, pharmacological and toxicological information about this new potential recreational drug.

Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.

PubMed

Wages, Phillip A; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M

2016-12-01

Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress☆,☆☆

PubMed Central

Wages, Phillip A.; Cheng, Wan-Yun; Gibbs-Flournoy, Eugene; Samet, James M.

2017-01-01

Background Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. Scope of review The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Major conclusions Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. General significance Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID:27208426

Spaceflight Toxicology

NASA Technical Reports Server (NTRS)

Meyers, Valerie

2008-01-01

This viewgraph presentation provides a review of NASA Johnson Space Center's Toxicology program. The mission of this program is to protect crews from toxic exposures during spaceflight. The presentation reviews some of the health hazards. A toxicological hazard level chart is presented that reviews the rating of hazard level, irritancy, systemic effects and containability. The program also participates in the Lunar Airborne Dust Toxicity Advisory Group.

Di-Isobutyl Phthalate (DIBP) Hazard Identification [Abstract ...

EPA Pesticide Factsheets

The hazard potential for DIBP is being evaluated as part of EPA’s Integrated Risk Information System (IRIS) Toxicological Review. DIBP is a plasticizer that confers flexibility and durability in industrial and consumer products. A literature search identified a relatively small epidemiology and animal toxicology database for DIBP. The epidemiological database includes studies that assessed the relationship between urinary concentrations of the DIBP metabolite mono-isobutyl phthalate (MIBP)and developmental, neurodevelopmental, immunological or breast cancer outcomes. There is limited support for associations between MIBP and inflammatory biomarker levels and decreased masculine play behavior. The animal toxicological database includes studies that assessed “phthalate syndrome” male reproductive developmental endpoints after in utero DIBP exposure. Data from the largest developmental study, Saillenfait et al. (2008), shows changes in anogenital distance, male reproductive organ weights, and litter incidence of phthalate syndrome endpoints in the lower dose range after early gestational exposure. Other studies observed increased fetal mortality, male postnatal and adult growth decrements, decreased fetal testicular testosterone and changes in expression of genes in androgen production pathways. The developmental reproductive effects observed in animal studies are consistent with the reduced testicular testosterone mode of action that is well-characterize

A toxicological review of the propylene glycols.

PubMed

Fowles, Jeff R; Banton, Marcy I; Pottenger, Lynn H

2013-04-01

The toxicological profiles of monopropylene glycol (MPG), dipropylene glycol (DPG), tripropylene glycol (TPG) and polypropylene glycols (PPG; including tetra-rich oligomers) are collectively reviewed, and assessed considering regulatory toxicology endpoints. The review confirms a rich data set for these compounds, covering all of the major toxicological endpoints of interest. The metabolism of these compounds share common pathways, and a consistent profile of toxicity is observed. The common metabolism provides scientific justification for adopting a read-across approach to describing expected hazard potential from data gaps that may exist for specific oligomers. None of the glycols reviewed presented evidence of carcinogenic, mutagenic or reproductive/developmental toxicity potential to humans. The pathologies reported in some animal studies either occurred at doses that exceeded experimental guidelines, or involved mechanisms that are likely irrelevant to human physiology and therefore are not pertinent to the exposures experienced by consumers or workers. At very high chronic doses, MPG causes a transient, slight decrease in hemoglobin in dogs and at somewhat lower doses causes Heinz bodies to form in cats in the absence of any clinical signs of anemia. Some evidence for rare, idiosyncratic skin reactions exists for MPG. However, the larger data set indicates that these compounds have low sensitization potential in animal studies, and therefore are unlikely to represent human allergens. The existing safety evaluations of the FDA, USEPA, NTP and ATSDR for these compounds are consistent and point to the conclusion that the propylene glycols present a very low risk to human health.

Effect of Manganese on some aspects of carbohydrate metabolism in rats. [None

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

Husain, R.; Mushtaq, M.; Seth, P.K.

1980-10-01

Numerous biochemical and toxicological studies have indicated that chronic exposure to manganese leads to neurological abnormalities. Increasing use of manganese compounds as antiknocks in gasoline and diesel fuel has aroused a great concern over the toxicological potential of this metal and stressed the need for understanding the mechanism of its poisoning. Reports of alerations in the levels of biogenic amines have helped in understanding the basis of neurological disorders. However, little is known about the mechanism by which manganese exposure leads to hypoglycemia in workers. This study deals with the influence of manganese exposure on metabolism of glucose, the chiefmore » fuel of the brain, and some enzymes involved in its oxidation. These studies will provide an assessment of the extent to which manganese affects the various processes controlling carbohydrate metabolism.« less

Toxicological assessment of Anionic Methacrylate Copolymer: I. Characterization, bioavailability and genotoxicity.

PubMed

Eisele, Johanna; Haynes, Geoff; Kreuzer, Knut; Hall, Caroline

2016-12-01

Anionic Methacrylate Copolymer (AMC) is a fully polymerized copolymer used in the pharmaceutical industry as an enteric/delayed-release coating to permit the pH-dependent release of active ingredients in the gastrointestinal tract from oral dosage forms. This function is of potential use for food supplements. Oral administration of radiolabeled copolymer to rats resulted in the detection of chemically unchanged copolymer in the feces, with negligible absorption (<0.1%). AMC is therefore determined not to be bioavailable. Within a genotoxicity test battery AMC did not show any evidence of genotoxicity in bacteria and mammalian cells. Furthermore, no genotoxic effects occurred in vivo within a micronucleus test. There would therefore appear to be no safety concerns under intended conditions of oral use for the discussed toxicological endpoints. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanistic modeling of pesticide exposure: The missing keystone of honey bee toxicology.

PubMed

Sponsler, Douglas B; Johnson, Reed M

2017-04-01

The role of pesticides in recent honey bee losses is controversial, partly because field studies often fail to detect effects predicted by laboratory studies. This dissonance highlights a critical gap in the field of honey bee toxicology: there exists little mechanistic understanding of the patterns and processes of exposure that link honey bees to pesticides in their environment. The authors submit that 2 key processes underlie honey bee pesticide exposure: 1) the acquisition of pesticide by foraging bees, and 2) the in-hive distribution of pesticide returned by foragers. The acquisition of pesticide by foraging bees must be understood as the spatiotemporal intersection between environmental contamination and honey bee foraging activity. This implies that exposure is distributional, not discrete, and that a subset of foragers may acquire harmful doses of pesticide while the mean colony exposure would appear safe. The in-hive distribution of pesticide is a complex process driven principally by food transfer interactions between colony members, and this process differs importantly between pollen and nectar. High priority should be placed on applying the extensive literature on honey bee biology to the development of more rigorously mechanistic models of honey bee pesticide exposure. In combination with mechanistic effects modeling, mechanistic exposure modeling has the potential to integrate the field of honey bee toxicology, advancing both risk assessment and basic research. Environ Toxicol Chem 2017;36:871-881. © 2016 SETAC. © 2016 SETAC.

Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model.

PubMed

Pereira, Talita Carneiro Brandão; Campos, Maria Martha; Bogo, Maurício Reis

2016-07-01

Copper is an essential micronutrient and a key catalytic cofactor in a wide range of enzymes. As a trace element, copper levels are tightly regulated and both its deficit and excess are deleterious to the organism. Under inflammatory conditions, serum copper levels are increased and trigger oxidative stress responses that activate inflammatory responses. Interestingly, copper dyshomeostasis, oxidative stress and inflammation are commonly present in several chronic diseases. Copper exposure can be easily modeled in zebrafish; a consolidated model in toxicology with increasing interest in immunity-related research. As a result of developmental, economical and genetic advantages, this freshwater teleost is uniquely suitable for chemical and genetic large-scale screenings, representing a powerful experimental tool for a whole-organism approach, mechanistic studies, disease modeling and beyond. Copper toxicological and more recently pro-inflammatory effects have been investigated in both larval and adult zebrafish with breakthrough findings. Here, we provide an overview of copper metabolism in health and disease and its effects on oxidative stress and inflammation responses in zebrafish models. Copper-induced inflammation is highlighted owing to its potential to easily mimic pro-oxidative and pro-inflammatory features that combined with zebrafish genetic tractability could help further in the understanding of copper metabolism, inflammatory responses and related diseases. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.

PubMed

Sewell, Fiona; Chapman, Kathryn; Baldrick, Paul; Brewster, David; Broadmeadow, Alan; Brown, Paul; Burns-Naas, Leigh Ann; Clarke, Janet; Constan, Alex; Couch, Jessica; Czupalla, Oliver; Danks, Andy; DeGeorge, Joseph; de Haan, Lolke; Hettinger, Klaudia; Hill, Marilyn; Festag, Matthias; Jacobs, Abby; Jacobson-Kram, David; Kopytek, Stephan; Lorenz, Helga; Moesgaard, Sophia Gry; Moore, Emma; Pasanen, Markku; Perry, Rick; Ragan, Ian; Robinson, Sally; Schmitt, Petra M; Short, Brian; Lima, Beatriz Silva; Smith, Diane; Sparrow, Sue; van Bekkum, Yvette; Jones, David

2014-10-01

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis rotundifolia triana (Melastomataceae)

PubMed Central

2010-01-01

Background The leaves of Dissotis rotundifolia are used ethnomedically across Africa without scientific basis or safety concerns. Determination of its phytochemical constituents, antimicrobial activity, effects on the gastrointestinal tract (GIT) as well as toxicological profile will provide supportive scientific evidence in favour of its continous usage. Method Chemical and chromatographic tests were employed in phytochemical investigations. Inhibitory activity against clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhi were compared with Gentamycin. Our report includes minimum inhibitory concentration (MIC) against the tested organisms. The effect of the ethanol extract on the motility of the GIT in mice using the charcoal plug method and castor oil induced diarrhoea in rats was evaluated. Toxicological evaluation was determined by administering 250 mg/kg and 500 mg/kg of extracts on male Wistar rats for 14 days with normal saline as control. The tissues of the kidneys, liver, heart and testes were examined. Results Phytochemical studies revealed the presence of alkaloids, saponin and cardiac glycosides. The crude ethanol extract and fractions inhibited the growth of E. coli, P. aeruginosa, S. aureus and S. typhi to varying extents. The degree of transition exhibited by the charcoal meal was dose-dependent. In the castor oil induced diarrhoea test, all the doses showed anti-spasmodic effects. The LD50 in mice was above 500 mg/kg body weight. Toxicological evaluation at 500 mg/kg showed increased cytoplasmic eosinophilia and densely stained nuclei of the liver, tubular necrosis of the kidney, presence of ill-defined testes with indistinct cell outlines and no remarkable changes in the heart. Conclusion Ethanol extracts of Dissotis rotundifolia have demonstrated antimicrobial activity against clinical strains of selected microorganisms. The plant showed potential for application in the treatment of diarrhoea, thereby justifying its usage across Africa. It also demonstrated toxicity in certain organs at the dose of 500 mg/kg, and it will be necessary to fully establish its safety profile. PMID:21083876

Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis rotundifolia Triana (Melastomataceae).

PubMed

Abere, Tavs A; Okoto, Pius E; Agoreyo, Freddy O

2010-11-17

The leaves of Dissotis rotundifolia are used ethnomedically across Africa without scientific basis or safety concerns. Determination of its phytochemical constituents, antimicrobial activity, effects on the gastrointestinal tract (GIT) as well as toxicological profile will provide supportive scientific evidence in favour of its continous usage. Chemical and chromatographic tests were employed in phytochemical investigations. Inhibitory activity against clinical strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Salmonella typhi were compared with Gentamycin. Our report includes minimum inhibitory concentration (MIC) against the tested organisms. The effect of the ethanol extract on the motility of the GIT in mice using the charcoal plug method and castor oil induced diarrhoea in rats was evaluated. Toxicological evaluation was determined by administering 250 mg/kg and 500 mg/kg of extracts on male Wistar rats for 14 days with normal saline as control. The tissues of the kidneys, liver, heart and testes were examined. Phytochemical studies revealed the presence of alkaloids, saponin and cardiac glycosides. The crude ethanol extract and fractions inhibited the growth of E. coli, P. aeruginosa, S. aureus and S. typhi to varying extents. The degree of transition exhibited by the charcoal meal was dose-dependent. In the castor oil induced diarrhoea test, all the doses showed anti-spasmodic effects. The LD50 in mice was above 500 mg/kg body weight. Toxicological evaluation at 500 mg/kg showed increased cytoplasmic eosinophilia and densely stained nuclei of the liver, tubular necrosis of the kidney, presence of ill-defined testes with indistinct cell outlines and no remarkable changes in the heart. Ethanol extracts of Dissotis rotundifolia have demonstrated antimicrobial activity against clinical strains of selected microorganisms. The plant showed potential for application in the treatment of diarrhoea, thereby justifying its usage across Africa. It also demonstrated toxicity in certain organs at the dose of 500 mg/kg, and it will be necessary to fully establish its safety profile.

Toxicological Risks During Human Space Exploration

NASA Technical Reports Server (NTRS)

James, John T.; Limero, T. F.; Lam, C. W.; Billica, Roger (Technical Monitor)

2000-01-01

The goal of toxicological risk assessment of human space flight is to identify and quantify significant risks to astronaut health from air pollution inside the vehicle or habitat, and to develop a strategy for control of those risks. The approach to completing a toxicological risk assessment involves data and experience on the frequency and severity of toxicological incidents that have occurred during space flight. Control of these incidents depends on being able to understand their cause from in-flight and ground-based analysis of air samples, crew reports of air quality, and known failures in containment of toxic chemicals. Toxicological risk assessment in exploration missions must be based on an evaluation of the unique toxic hazards presented by the habitat location. For example, lunar and Martian dust must be toxicologically evaluated to determine the appropriate control measures for exploration missions. Experience with near-earth flights has shown that the toxic products from fires present the highest risk to crew health from air pollution. Systems and payload leaks also present a significant hazard. The health risk from toxicity associated with materials offgassing or accumulation of human metabolites is generally well controlled. Early tests of lunar and Martian dust simulants have shown that each posses the potential to cause fibrosis in the lung in a murine model. Toxicological risks from air pollutants in space habitats originate from many sources. A number of risks have been identified through near-earth operations; however, the evaluation of additional new risks present during exploration missions will be a challenge.

Retrospective Mining of Toxicology Data to Discover Multispecies Effects: Anemia as a Case Study (SOT)

EPA Science Inventory

In vivo toxicology data is subject to multiple sources of uncertainty: observer severity bias (a pathologist may record only more severe effects and ignore less severe ones); dose spacing issues (this can lead to missing data, e.g. if a severe effect has a less severe precursor, ...

Reducing impacts from ammunitions: A comparative life-cycle assessment of four types of 9mm ammunitions.

PubMed

Ferreira, Carlos; Ribeiro, José; Almada, Sara; Rotariu, Traian; Freire, Fausto

2016-10-01

Increase of environmental awareness of the population has pressured research activities in the defence area to cover environment and toxicity issues, where have been considered appropriate manners to reduce the environmental and toxicological impacts of ammunition. One of the adopted approaches to achieve such goal involves the replacement of lead and other heavy metals by alternative materials. However, the consequences of using alternative materials in ammunitions manufacturing are uncertain for the other life-cycle phases and trade-offs can occur. The present paper describes the potential benefits from the replacement of lead in the primer and in the projectile of a 9mm calibre ammunition. For that purpose, it is assessed and compared the environmental and toxicological impacts associated with the life-cycle of four ammunitions: combination of two types of projectiles (steel jacket and lead core; copper and nylon composite) with two types of primers (lead primer; non-lead primer). In addition, some potential improvements for the environmental performance of small calibre ammunition are also presented. To assess the impacts two Life-Cycle Impact Assessment methods are applied: CML for six environmental categories and USEtox to three toxicity categories. Results showed that the conclusion drawn for environmental and toxicological impact categories are distinct. In fact, ammunition production phase presents higher impacts for the environmental categories, whilst the operation phase has a higher impact to the toxicity categories. The substitution of lead in the primer and in the projectile provides a suitable alternative from a toxicology perspective; however, the composite projectile still presents some environmental concerns. The conclusions drawn are important for the procurement (and design) of environmental responsible ammunitions, in order to avoid (or decrease) the impacts for their manufacture and the effects on human health (e.g. shooters) and ecosystems near shooting ranges or hunting areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving substance information in USEtox® , part 2: Data for estimating fate and ecosystem exposure factors.

PubMed

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

2017-12-01

The scientific consensus model USEtox ® has been developed since 2003 under the auspices of the United Nations Environment Programme-Society of Environmental Toxicology and Chemistry Life Cycle Initiative as a harmonized approach for characterizing human and freshwater toxicity in life cycle assessment and other comparative assessment frameworks. Using physicochemical substance properties, USEtox quantifies potential human toxicity and freshwater ecotoxicity impacts by combining environmental fate, exposure, and toxicity effects information, considering multimedia fate and multipathway exposure processes. The main source to obtain substance properties for USEtox 1.01 and 2.0 is the Estimation Program Interface (EPI Suite™) from the US Environmental Protection Agency. However, since the development of the original USEtox substance databases, new chemical regulations have been enforced in Europe, such as the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and the Plant Protection Products regulations. These regulations require that a chemical risk assessment for humans and the environment is performed before a chemical is placed on the European market. Consequently, additional physicochemical property data and new toxicological endpoints are now available for thousands of chemical substances. The aim of the present study was to explore the extent to which the new available data can be used as input for USEtox-especially for application in environmental footprint studies-and to discuss how this would influence the quantification of fate and exposure factors. Initial results show that the choice of data source and the parameters selected can greatly influence fate and exposure factors, leading to potentially different rankings and relative contributions of substances to overall human toxicity and ecotoxicity impacts. Moreover, it is crucial to discuss the relevance of the exposure factor for freshwater ecotoxicity impacts, particularly for persistent highly adsorbing and bioaccumulating substances. Environ Toxicol Chem 2017;36:3463-3470. © 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.

A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum.

PubMed

Li, Shuping; Cheng, Xuemei; Wang, Changhong

2017-05-05

The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research. Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS's dissertations. The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory. Based on this review, there is some evidence for extracts' pharmacological effects on Alzheimer's and Parkinson's diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding many aspects of the genus such as mechanisms of actions, metabolism, pharmacokinetics, toxicology, potential drug interactions with standard-of-care medications is still limited which call for additional studies particularly in humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Toxicological aspects of fire.

PubMed

Stefanidou, M; Athanaselis, S

2004-08-01

Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases. As a wide variety of synthetic materials is used in buildings (insulation, furniture, carpeting, electric wiring covering, decorative items), the potential for poisoning from inhalation of products of combustion is continuously increasing. In the present review, the problems that are present in a fire event, the toxicology of the toxic substances and the specific chemical hazards to firefighters are described. Regulatory toxicology aspects are presented concerning the use of non-flammable building and furnishing materials to prevent fires and decrease of poisonings and deaths resulting from fires.

From the Cover: Development and Application of a Dual Rat and Human AHR Activation Assay.

PubMed

Brown, Martin R; Garside, Helen; Thompson, Emma; Atwal, Saseela; Bean, Chloe; Goodall, Tony; Sullivan, Michael; Graham, Mark J

2017-12-01

Significant prolonged aryl hydrocarbon receptor (AHR) activation, classically exhibited following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, can cause a variety of undesirable toxicological effects. Novel pharmaceutical chemistries also have the potential to cause activation of AHR and consequent toxicities in pre-clinical species and man. Previous methods either employed relatively expensive and low-throughput primary hepatocyte dosing with PCR endpoint, or low resolution overexpressing reporter gene assays. We have developed, validated and applied an in vitro microtitre plate imaging-based medium throughput screening assay for the assessment of endogenous species-specific AHR activation potential via detection of induction of the surrogate transcriptional target Cytochrome P450 CYP1A1. Routine testing of pharmaceutical drug development candidate chemistries using this assay can influence the chemical design process and highlight AHR liabilities. This assay should be introduced such that human AHR activation liability is flagged early for confirmatory testing. © 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.

Developmental neurotoxicity and autism: A potential link between indoor neuroactive pollutants and the curious birth order risk factor.

PubMed

Gray, Wesley A; Billock, Vincent A

2017-11-01

Epidemiological and demographic studies find an increased risk of autism among first-borns. Toxicological studies show that some semi-volatile substances found in infant products produce adverse effects in neural and endocrine systems of animals, including behavioral and developmental effects. Several factors elevate the exposure of human infants to these chemicals. The highest exposures found in infants are comparable to the exposures that induce neural toxicity in animals. A review of these literatures suggests a linking hypothesis that could bridge the epidemiological and toxicological lines of evidence: an infant's exposure to neuroactive compounds emitted by infant products is increased by product newness and abundance; exposure is likely maximized for first-born children in families that can afford new products. Exposure is reduced for subsequently-born children who reuse these now neuroactive-depleted products. The presence of neuroactive chemical emissions from infant products has implications for birth-order effects and for other curious risk factors in autism, including gender, socioeconomic status, and season-of-birth risk factors. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Potential Interference of Oil Vehicles on Genital Tubercle Development during the Fetal Period in ICR Mice.

PubMed

Nishioka, Yasushi; Tamai, Kazuki; Onda, Masanari; Hiromori, Youhei; Kimura, Tomoki; Hu, Jianying; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2018-01-01

Corn oil, sesame oil, and 10% ethanol in corn oil are commonly used as dosing vehicles in toxicology studies. Since these vegetable oils contain bioactive compounds, it is important for toxicology studies to characterize the toxicities of the dosing vehicles themselves. It has been recently proposed that the width of the genital tubercle (GT), the dorsal-ventral length (D-V length) of the GT, and urethral tube closure in mouse fetuses can be used as novel markers for monitoring sexual development in mice. However, how these parameters are influenced by the dosing vehicles themselves remains unclear. Therefore, we evaluated the effects of corn oil, sesame oil, and 10% ethanol in corn oil on GT width, D-V length, and GT morphology in ICR mice. Our results showed that all three vehicles influenced GT width and D-V length, but not GT morphology, suggesting that the effects of dosing vehicles themselves might need to be considered when GT width or D-V length is used as a parameter to evaluate the effects of chemicals on GT development.

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.

High-Throughput Analysis of Ovarian Cycle Disruption by Mixtures of Aromatase Inhibitors

PubMed Central

Golbamaki-Bakhtyari, Nazanin; Kovarich, Simona; Tebby, Cleo; Gabb, Henry A.; Lemazurier, Emmanuel

2017-01-01

Background: Combining computational toxicology with ExpoCast exposure estimates and ToxCast™ assay data gives us access to predictions of human health risks stemming from exposures to chemical mixtures. Objectives: We explored, through mathematical modeling and simulations, the size of potential effects of random mixtures of aromatase inhibitors on the dynamics of women's menstrual cycles. Methods: We simulated random exposures to millions of potential mixtures of 86 aromatase inhibitors. A pharmacokinetic model of intake and disposition of the chemicals predicted their internal concentration as a function of time (up to 2 y). A ToxCast™ aromatase assay provided concentration–inhibition relationships for each chemical. The resulting total aromatase inhibition was input to a mathematical model of the hormonal hypothalamus–pituitary–ovarian control of ovulation in women. Results: Above 10% inhibition of estradiol synthesis by aromatase inhibitors, noticeable (eventually reversible) effects on ovulation were predicted. Exposures to individual chemicals never led to such effects. In our best estimate, ∼10% of the combined exposures simulated had mild to catastrophic impacts on ovulation. A lower bound on that figure, obtained using an optimistic exposure scenario, was 0.3%. Conclusions: These results demonstrate the possibility to predict large-scale mixture effects for endocrine disrupters with a predictive toxicology approach that is suitable for high-throughput ranking and risk assessment. The size of the effects predicted is consistent with an increased risk of infertility in women from everyday exposures to our chemical environment. https://doi.org/10.1289/EHP742 PMID:28886606

Azadirachtin induced apoptosis in the prothoracic gland in Bombyx mori and a pronounced Ca2+ release effect in Sf9 cells

PubMed Central

Zhang, Jing; Liu, Hongmei; Sun, Zhipeng; Xie, Jianjun; Zhong, Guohua; Yi, Xin

2017-01-01

Azadirachtin is a bio-rational insecticide used as an antifeedant and growth disruption agent against many insect species. However, recent studies have shown that there is a potential risk of this compound harming some beneficial insects. In such cases its application does not normally lead to death, but it may result in altered developmental regulation. Therefore, it is essential to obtain toxicological data to understand the mechanism of such sub-lethal effects, especially where they relate to important beneficial insects. Here, we found that azadirachtin could regulate growth and cocooning in silkworms, which may be associated with induced apoptotic effect on the prothoracic gland. However, azadirachtin treatment could not induce apoptosis in the prothoracic gland in vitro, in contrast to the effect of 20-hydroxyecdysone in vitro, which suggesting that the apoptosis might not be direct effect of azadirachtin. Then we examined the activity of Ca2+-Mg2+-ATPase and found that azadirachtin could trigger a significant increase in intracellular Ca2+ release in the Sf9 cell line, which suggested that the calcium signaling pathway might be involved in the process of apoptosis in prothoracic gland and growth regulation in vivo silkworms. Although more evidence is needed to fully understand the mechanism of azadirachtin in perturbing the growth of silkworms, this study provides some toxicological information and highlights the potential risks of azadirachtin in relation to silkworms. PMID:29230101

Azadirachtin induced apoptosis in the prothoracic gland in Bombyx mori and a pronounced Ca2+ release effect in Sf9 cells.

PubMed

Zhang, Jing; Liu, Hongmei; Sun, Zhipeng; Xie, Jianjun; Zhong, Guohua; Yi, Xin

2017-01-01

Azadirachtin is a bio-rational insecticide used as an antifeedant and growth disruption agent against many insect species. However, recent studies have shown that there is a potential risk of this compound harming some beneficial insects. In such cases its application does not normally lead to death, but it may result in altered developmental regulation. Therefore, it is essential to obtain toxicological data to understand the mechanism of such sub-lethal effects, especially where they relate to important beneficial insects. Here, we found that azadirachtin could regulate growth and cocooning in silkworms, which may be associated with induced apoptotic effect on the prothoracic gland. However, azadirachtin treatment could not induce apoptosis in the prothoracic gland in vitro , in contrast to the effect of 20-hydroxyecdysone in vitro, which suggesting that the apoptosis might not be direct effect of azadirachtin. Then we examined the activity of Ca 2+ -Mg 2+ -ATPase and found that azadirachtin could trigger a significant increase in intracellular Ca 2+ release in the Sf9 cell line, which suggested that the calcium signaling pathway might be involved in the process of apoptosis in prothoracic gland and growth regulation in vivo silkworms. Although more evidence is needed to fully understand the mechanism of azadirachtin in perturbing the growth of silkworms, this study provides some toxicological information and highlights the potential risks of azadirachtin in relation to silkworms.

Principles and procedures in forensic toxicology.

PubMed

Wyman, John F

2012-09-01

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

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

PubMed Central

Zanon, Tyler; Kappell, Anthony D.; Petrella, Lisa N.; Andersen, Erik C.; Hristova, Krassimira R.

2016-01-01

Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress). PMID:27911941

Occurrence of 210Po and Biological Effects of Low-Level Exposure: The Need for Research

PubMed Central

Wiemels, Joseph L.

2012-01-01

Background: Polonium-210 (210Po) concentrations that exceed 1 Bq/L in drinking-water supplies have been reported from four widely separated U.S. states where exposure to it went unnoticed for decades. The radionuclide grandparents of 210Po are common in sediments, and segments of the public may be chronically exposed to low levels of 210Po in drinking water or in food products from animals raised in contaminated areas. Objectives: We summarized information on the environmental behavior, biokinetics, and toxicology of 210Po and identified the need for future research. Methods: Potential linkages between environmental exposure to 210Po and human health effects were identified in a literature review. Discussion: 210Po accumulates in the ovaries where it kills primary oocytes at low doses. Because of its radiosensitivity and tendency to concentrate 210Po, the ovary may be the critical organ in determining the lowest injurious dose for 210Po. 210Po also accumulates in the yolk sac of the embryo and in the fetal and placental tissues. Low-level exposure to 210Po may have subtle, long-term biological effects because of its tropism towards reproductive and embryonic and fetal tissues where exposure to a single alpha particle may kill or damage critical cells. 210Po is present in cigarettes and maternal smoking has several effects that appear consistent with the toxicology of 210Po. Conclusions: Much of the important biological and toxicological research on 210Po is more than four decades old. New research is needed to evaluate environmental exposure to 210Po and the biological effects of low-dose exposure to it so that public health officials can develop appropriate mitigation measures where necessary. PMID:22538346

Antituberculous effect of silver nanoparticles

NASA Astrophysics Data System (ADS)

Kreytsberg, G. N.; Gracheva, I. E.; Kibrik, B. S.; Golikov, I. V.

2011-04-01

The in vitro experiment, involving 1164 strains of the tuberculosis mycobacteria, exhibited a potentiating effect of silver nanoparticles on known antituberculous preparations in respect of overcoming drug-resistance of the causative agent. The in vitro experiment, based on the model of resistant tuberculosis, was performed on 65 white mice. An evident antituberculous effect of the nanocomposite on the basis of silver nanoparticles and isoniazid was proved. Toxicological assessment of the of nanopreparations was carried out. The performed research scientifically establishes efficacy and safety of the nanocomposite application in combination therapy of patients suffering from drug-resistant tuberculosis.

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.

Mechanism of Action of Lung Damage Caused by a Nanofilm Spray Product

PubMed Central

Larsen, Søren T.; Dallot, Constantin; Larsen, Susan W.; Rose, Fabrice; Poulsen, Steen S.; Nørgaard, Asger W.; Hansen, Jitka S.; Sørli, Jorid B.; Nielsen, Gunnar D.; Foged, Camilla

2014-01-01

Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolized product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these products may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studies. Thus, because the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products. PMID:24863969

Towards science-based sediment quality standards-Effects of field-collected sediments in rainbow trout (Oncorhynchus mykiss).

PubMed

Brinkmann, Markus; Eichbaum, Kathrin; Reininghaus, Mathias; Koglin, Sven; Kammann, Ulrike; Baumann, Lisa; Segner, Helmut; Zennegg, Markus; Buchinger, Sebastian; Reifferscheid, Georg; Hollert, Henner

2015-09-01

Sediments can act as long-term sinks for environmental pollutants. Within the past decades, dioxin-like compounds (DLCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) have attracted significant attention in the scientific community. To investigate the time- and concentration-dependent uptake of DLCs and PAHs in rainbow trout (Oncorhynchus mykiss) and their associated toxicological effects, we conducted exposure experiments using suspensions of three field-collected sediments from the rivers Rhine and Elbe, which were chosen to represent different contamination levels. Five serial dilutions of contaminated sediments were tested; these originated from the Prossen and Zollelbe sampling sites (both in the river Elbe, Germany) and from Ehrenbreitstein (Rhine, Germany), with lower levels of contamination. Fish were exposed to suspensions of these dilutions under semi-static conditions for 90 days. Analysis of muscle tissue by high resolution gas chromatography and mass spectrometry and of bile liquid by high-performance liquid chromatography showed that particle-bound PCDD/Fs, PCBs and PAHs were readily bioavailable from re-suspended sediments. Uptake of these contaminants and the associated toxicological effects in fish were largely proportional to their sediment concentrations. The changes in the investigated biomarkers closely reflected the different sediment contamination levels: cytochrome P450 1A mRNA expression and 7-ethoxyresorufin-O-deethylase activity in fish livers responded immediately and with high sensitivity, while increased frequencies of micronuclei and other nuclear aberrations, as well as histopathological and gross pathological lesions, were strong indicators of the potential long-term effects of re-suspension events. Our study clearly demonstrates that sediment re-suspension can lead to accumulation of PCDD/Fs and PCBs in fish, resulting in potentially adverse toxicological effects. For a sound risk assessment within the implementation of the European Water Framework Directive and related legislation, we propose a strong emphasis on sediment-bound contaminants in the context of integrated river basin management plans. Copyright © 2015 Elsevier B.V. All rights reserved.

Taking stock of the occupational safety and health challenges of nanotechnology: 2000-2015

NASA Astrophysics Data System (ADS)

Schulte, P. A.; Roth, G.; Hodson, L. L.; Murashov, V.; Hoover, M. D.; Zumwalde, R.; Kuempel, E. D.; Geraci, C. L.; Stefaniak, A. B.; Castranova, V.; Howard, J.

2016-06-01

Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required.

Taking stock of the occupational safety and health challenges of nanotechnology: 2000-2015.

PubMed

Schulte, P A; Roth, G; Hodson, L L; Murashov, V; Hoover, M D; Zumwalde, R; Kuempel, E D; Geraci, C L; Stefaniak, A B; Castranova, V; Howard, J

2016-06-01

Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required.

An epidemiological and toxicological evaluation of the carcinogenicity of man-made vitreous fiber, with a consideration of coexposures.

PubMed

Wong, O; Musselman, R P

1994-01-01

Exposure to man-made mineral (or vitreous) fiber (MMMF or MMVF) is a potential health concern in both occupational and environmental settings. Previous epidemiologic studies have reported a small increase of lung cancer among workers exposed to MMVF. Most of these studies were cohort studies and lacked information on fiber concentration, occupational coexposures, and cigarette smoking. Some of the coexposures were known human lung carcinogens and could have accounted for the small lung cancer excess. In a recently completed epidemiologic case-control study of lung cancer in MMVF workers exposed to slag wool fibers, we analyzed lung cancer risk in relation to cumulative fiber exposure (concentration and duration) and smoking history and controlled for other coexposures such as asbestos contamination. No increased lung cancer risk with exposure to slag wool fibers was found. As expected, however, we detected a strong confounding effect of smoking. The findings from this epidemiologic study were consistent with the results of recently completed toxicologic studies, which found that slag wool fibers of dimension classically associated with tumor induction ("Stanton" fibers) do not stay in the lung in sufficient quantity or time to induce tumors in animals. In this paper we emphasize the importance of confounding effects due to coexposures and provide guidelines to estimate the magnitude of potential confounding effects of coexposures such as smoking.

Nanofiller Presence Enhances Polycyclic Aromatic Hydrocarbon (PAH) Profile on Nanoparticles Released during Thermal Decomposition of Nano-enabled Thermoplastics: Potential Environmental Health Implications.

PubMed

Singh, Dilpreet; Schifman, Laura Arabella; Watson-Wright, Christa; Sotiriou, Georgios A; Oyanedel-Craver, Vinka; Wohlleben, Wendel; Demokritou, Philip

2017-05-02

Nano-enabled products are ultimately destined to reach end-of-life with an important fraction undergoing thermal degradation through waste incineration or accidental fires. Although previous studies have investigated the physicochemical properties of released lifecycle particulate matter (called LCPM) from thermal decomposition of nano-enabled thermoplastics, critical questions about the effect of nanofiller on the chemical composition of LCPM still persist. Here, we investigate the potential nanofiller effects on the profiles of 16 Environmental Protection Agency (EPA)-priority polycyclic aromatic hydrocarbons (PAHs) adsorbed on LCPM from thermal decomposition of nano-enabled thermoplastics. We found that nanofiller presence in thermoplastics significantly enhances not only the total PAH concentration in LCPM but most importantly also the high molecular weight (HMW, 4-6 ring) PAHs that are considerably more toxic than the low molecular weight (LMW, 2-3 ring) PAHs. This nano-specific effect was also confirmed during in vitro cellular toxicological evaluation of LCPM for the case of polyurethane thermoplastic enabled with carbon nanotubes (PU-CNT). LCPM from PU-CNT shows significantly higher cytotoxicity compared to PU which could be attributed to its higher HMW PAH concentration. These findings are crucial and make the case that nanofiller presence in thermoplastics can significantly affect the physicochemical and toxicological properties of LCPM released during thermal decomposition.

Taking stock of the occupational safety and health challenges of nanotechnology: 2000–2015

PubMed Central

Roth, G.; Hodson, L. L.; Murashov, V.; Hoover, M. D.; Zumwalde, R.; Kuempel, E. D.; Geraci, C. L.; Stefaniak, A. B.; Castranova, V.; Howard, J.

2016-01-01

Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required. PMID:27594804

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.

Teaching Toxicology as a Basic Medical Science

ERIC Educational Resources Information Center

Gralla, Edward J.

1976-01-01

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

Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

EPA Science Inventory

EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

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

EPA Science Inventory

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

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

Human Cell Line Activation Test of the Novel Energetics Methyl Trinitropryrazol (MTNP) and 1,3-Dimethylhexahydropyrimidine (DHP)

DTIC Science & Technology

2017-11-01

costs, conserve physical resources, and sustain the health of those potentially exposed. The U.S. Army RDECOM, ETAP has been dedicated to finding...trinitropryrazol (MTNP) and 1,3-dimethylhexahydropyrimidine (DHP) Prepared by: Emily Reinke, Ph.D. Health Effects Division Toxicology...the Novel Energetics methyl trinitropyrazol (MTNP) and 1,3-dimethylhexahydropyrimidine (DHP) Emily N. Reinke, Ph.D. Army Public Health Center

Bio-oils from biomass slow pyrolysis: a chemical and toxicological screening.

PubMed

Cordella, Mauro; Torri, Cristian; Adamiano, Alessio; Fabbri, Daniele; Barontini, Federica; Cozzani, Valerio

2012-09-15

Bio-oils were produced from bench-scale slow-pyrolysis of three different biomass samples (corn stalks, poplar and switchgrass). Experimental protocols were developed and applied in order to screen their chemical composition. Several hazardous compounds were detected in the bio-oil samples analysed, including phenols, furans and polycyclic aromatic hydrocarbons. A procedure was outlined and applied to the assessment of toxicological and carcinogenic hazards of the bio-oils. The following hazardous properties were considered: acute toxicity; ecotoxicity; chronic toxicity; carcinogenicity. Parameters related to these properties were quantified for each component identified in the bio-oils and overall values were estimated for the bio-oils. The hazard screening carried out for the three bio-oils considered suggested that: (i) hazards to human health could be associated with chronic exposures to the bio-oils; (ii) acute toxic effects on humans and eco-toxic effects on aquatic ecosystems could also be possible in the case of loss of containment; and (iii) bio-oils may present a marginal potential carcinogenicity. The approach outlined allows the collection of screening information on the potential hazards posed by the bio-oils. This can be particularly useful when limited time and analytical resources reduce the possibility to obtain detailed specific experimental data. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed Central

2014-01-01

Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture. PMID:25177222

Space Toxicology: Environmental Health Considerations during Spaceflight Operations and Potential Paths for Research

NASA Technical Reports Server (NTRS)

Khan-Mayberry, Noreen N.; Sundaresan, Alemalu

2009-01-01

Space Toxicology is a specialized discipline for spaceflight, space habitation and occupation of celestial bodies including planets, moons and asteroids [1]. Astronaut explorers face unique challenges to their health while working and living with limited resources for rescue and medical care during space operation. At its core the practice of space toxicology to identify, assess and predict potential chemical contaminants and limit the astronaut s exposure to these environmental factors in order to protect crew health. Space toxicologists are also charged with setting safe exposure limits that will protect the astronaut against a multitude of chemical exposures, in a physiologically altered state. In order to maintain sustained occupation in space, toxicological risks are gauged and managed within the context of isolation, continual exposures, reuse of air and water, limited rescue options, and the necessary use of highly toxic compounds required for propulsion. As the space program move towards human presence and exploration other celestial bodies in situ toxicological risks, such as inhalation of unusual and/or reactive mineral dusts must also be analyzed and controlled. Placing humans for long-term presence in space creates several problems and challenges to the long-term health of the crew, such as bone-loss and immunological challenges and has spurred research into acute, chronic and episodic exposure of the pulmonary system to mineral dusts [2]. NASA has demonstrated that lunar soil contains several types of reactive dusts, including an extremely fine respirable component. In order to protect astronaut health, NASA is now investigating the toxicity of this unique class of dusts. Understanding how these reactive components behave "biochemically" in a moisture-rich pulmonary environment will aid in determining how toxic these particles are to humans. The data obtained from toxicological examination of lunar dusts will determine the human risk criteria for lunar dust exposure and produce a lunar health standard.

Systems Toxicology: Real World Applications and Opportunities.

PubMed

Hartung, Thomas; FitzGerald, Rex E; Jennings, Paul; Mirams, Gary R; Peitsch, Manuel C; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F; Sturla, Shana J

2017-04-17

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

Systems Toxicology: Real World Applications and Opportunities

PubMed Central

2017-01-01

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity. PMID:28362102

Prospects for Applying Synthetic Biology to Toxicology: Future Opportunities and Current Limitations for the Repurposing of Cytochrome P450 Systems.

PubMed

Behrendorff, James B Y H; Gillam, Elizabeth M J

2017-01-17

The 30 years since the inception of Chemical Research in Toxicology, game-changing advances in chemical and molecular biology, the fundamental disciplines underpinning molecular toxicology, have been made. While these have led to important advances in the study of mechanisms by which chemicals damage cells and systems, there has been less focus on applying these advances to prediction, detection, and mitigation of toxicity. Over the last ∼15 years, synthetic biology, the repurposing of biological "parts" in systems engineered for useful ends, has been explored in other areas of the biomedical and life sciences, for such applications as detecting metabolites, drug discovery and delivery, investigating disease mechanisms, improving medical treatment, and producing useful chemicals. These examples provide models for the application of synthetic biology to toxicology, which, for the most part, has not yet benefited from such approaches. In this perspective, we review the synthetic biology approaches that have been applied to date and speculate on possible short to medium term and "blue sky" aspirations for synthetic biology, particularly in clinical and environmental toxicology. Finally, we point out key hurdles that must be overcome for the full potential of synthetic biology to be realized.

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

Calabrese, Edward J.

This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and 'traditional' medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- andmore » public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment.« less

Metal tissue levels in Steller sea lion (Eumetopias jubatus) pups.

PubMed

Holmes, Amie L; Wise, Sandra S; Goertz, Caroline E C; Dunn, J Lawrence; Gulland, Frances M D; Gelatt, Tom; Beckmen, Kimberlee B; Burek, Kathy; Atkinson, Shannon; Bozza, Mary; Taylor, Robert; Zheng, Tongzhang; Zhang, Yawei; Aboueissa, Abouel-Makarim; Wise, John Pierce

2008-08-01

The endangered Western population of the Steller sea lion declined for three decades for uncertain reasons. We present baseline data of metal concentrations in pups as a first step towards investigating the potential threat of developmental exposures to contaminants. Seven metals were investigated: arsenic, cadmium, silver, aluminum, mercury, lead and vanadium. Vanadium was detected in only a single blubber sample. Mercury appears to be the most toxicologically significant metal with concentrations in the liver well above the current action level for mercury in fish. The concentrations of aluminum, arsenic, silver, cadmium and lead were present in one-fourth to two-thirds of all samples and were at either comparable or below concentrations previously reported. Neither gender nor region had a significant effect on metal burdens. Future work should consider metal concentrations in juveniles and adults and toxicological studies need to be performed to begin to assess the toxicity of these metals.

Toxicogenomics and clinical toxicology: an example of the connection between basic and applied sciences.

PubMed

Ferrer-Dufol, Ana; Menao-Guillen, Sebastian

2009-04-10

The relationship between basic research and its potential clinical applications is often a difficult subject. Clinical toxicology has always been very dependent on experimental research whose usefulness has been impaired by the existence of huge differences in the toxicity expression of different substances, inter- and intra-species which make it difficult to predict clinical effects in humans. The new methods in molecular biology developed in the last decades are furnishing very useful tools to study some of the more relevant molecules implied in toxicokinetic and toxicodynamic processes. We aim to show some meaningful examples of how recent research developments with genes and proteins have clear applications to understand significant clinical matters, such as inter-individual variations in susceptibility to chemicals, and other phenomena related to the way some substances act to induce variations in the expression and functionality of these targets.

Nontargeted multicomponent analytical screening of plastic food contact materials using fast interpretation of deliverables via expert structure-activity relationship software.

PubMed

Rothenbacher, Thorsten; Schwack, Wolfgang

2009-01-01

Plastic packaging materials may release compounds into packed foodstuffs. To identify potential migrants of toxicological concern, resins, and multilayer foils (mainly polyethylene) intended for the production of food contact materials were extracted and analyzed by GC/mass spectrometry. To identify even compounds of low concentrations, AMDIS software was used and data evaluation was safeguarded by the Kovats retention index (RI) system. In this way, 46 compounds were identified as possible migrants. The expert structure-activity relationship software DEREK for Windows was utilized to evaluate all identified substances in terms of carcinogenicity, genotoxicity, thyroid toxicity, and miscellaneous endpoints for humans. Additionally, a literature search for these compounds was performed with Sci-Finder, but relevant data were missing for 28 substances. Seven compounds with adverse toxicological effects were identified. In addition, the RIs of 24 commercial additive standards, measured with a GC capillary column of intermediate polarity, are given.

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.

Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80.

PubMed

Sellers, Rani S; Antman, M; Phillips, J; Khan, K N; Furst, S M

2005-01-01

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

Predicting EMP hazard: Lessons from studies with inhaled fibrous and non-fibrous nano- and micro-particles.

PubMed

Oberdörster, Günter; Graham, Uschi

2018-05-08

Inhalation exposure to elongated cleavage fragments occurring at mineral and rock mining and crushing operations raises important questions regarding potential health effects given their resemblance to fibers with known adverse health effects like amphibole asbestos. Thus, a major goal for establishing a toxicity profile for elongate mineral particles (EMPs) is to identify and characterize a suspected hazard and characterize a risk by examining together results of hazard and exposure assessment. This will require not only knowledge about biokinetics of inhaled EMPs but also about underlying mechanisms of effects induced by retained EMPs. In vitro toxicity assays with predictive power for in vivo effects have been established as useful screening tools for toxicological characterization of particulate materials including EMPs. Important determinants of physiological/toxicological mechanisms are physico-chemical and functional properties of inhaled particulate materials. Of the physico-chemical (intrinsic) properties, size, shape and surface characteristics are well known to affect toxicological responses; functional properties include (i) solubility/dissolution rate in physiological fluid simulants in vitro and following inhalation in vivo; (ii) ROS-inducing capacity in vitro and in vivo determined as specific particle surface reactivity; (iii) bioprocessing in vivo. A key parameter for all is the dose and duration of exposure, requiring to establish exposure-dose-response relationships. Examples of studies with fibrous and non-fibrous particles are discussed to illustrate the relevancy of evaluating extrinsic and intrinsic particle properties for predicting in vivo responses of new particulate materials. This will allow hazard and risk ranking/grouping based on a comparison to toxicologically well-characterized positive and negative benchmarks. Future efforts should be directed at developing and validating new approaches using in vitro (non-animal) studies for establishing a complete risk assessment for EMPs. Further comparative in-depth analyses with analytical and ultra-high resolution technology examining bioprocessing events at target organ sites have proven highly successful to identify biotransformations in target cells at near atomic level. In the case of EMPs, such analyses can be essential to separate benign from harmful ones. Copyright © 2018. Published by Elsevier Inc.

[Two cases of suspected Munchausen by proxy syndrome: the importance of forensic toxicological analyses in handling suspicions and producing evidence].

PubMed

Musshoff, Frank; Kirschbaum, Katrin M; Madea, Burkhard

2008-01-01

The authors report on two cases of suspected Munchausen by proxy syndrome. In a 3-year-old boy, clinical toxicological analyses produced suspicious clues that an antidepressant had been administered, which could not be verified by forensic toxicological investigations. In a 13-month-old boy, the mother was also suspected of having poisoned the child. Initial clinical toxicological examinations failed to explain the observed symptoms (unclear unconsciousness, narrowed pupils). While in the first case, the incorrect interpretation of findings by a laboratory without forensic experience resulted in suspicions against the mother, the cause for the observed symptoms in the second case could be proved by complex analyses not performed before and the suspicion that the clinical picture had been intentionally brought about could be cleared up (use of an antitussive containing clobutinol). The two reports show that especially in cases with a potential forensic background, adequately qualified forensic laboratories with a broad spectrum of analytical methods should be involved.

Applied Nanotoxicology.

PubMed

Hobson, David W; Roberts, Stephen M; Shvedova, Anna A; Warheit, David B; Hinkley, Georgia K; Guy, Robin C

2016-01-01

Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of interest to toxicologists such as pharmaceuticals, cosmetics, food, food packaging, household products, and so on. The manufacturing of products containing or utilizing nanomaterials in their composition may also present potential toxicologic concerns in the workplace. The molecular complexity and composition of these nanomaterials are ever increasing, and the means and methods being applied to characterize and perform useful toxicologic assessments are rapidly advancing. This article includes presentations by experienced toxicologists in the nanotoxicology community who are focused on the applied aspect of the discipline toward supporting state of the art toxicologic assessments for food products and packaging, pharmaceuticals and medical devices, inhaled nanoparticle and gastrointestinal exposures, and addressing occupational safety and health issues and concerns. This symposium overview article summarizes 5 talks that were presented at the 35th Annual meeting of the American College of Toxicology on the subject of "Applied Nanotechnology." © The Author(s) 2016.

Applied Nanotoxicology

PubMed Central

Hobson, David W.; Roberts, Stephen M.; Shvedova, Anna A.; Warheit, David B.; Hinkley, Georgia K.; Guy, Robin C.

2016-01-01

Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of interest to toxicologists such as pharmaceuticals, cosmetics, food, food packaging, household products, and so on. The manufacturing of products containing or utilizing nanomaterials in their composition may also present potential toxicologic concerns in the workplace. The molecular complexity and composition of these nanomaterials are ever increasing, and the means and methods being applied to characterize and perform useful toxicologic assessments are rapidly advancing. This article includes presentations by experienced toxicologists in the nanotoxicology community who are focused on the applied aspect of the discipline toward supporting state of the art toxicologic assessments for food products and packaging, pharmaceuticals and medical devices, inhaled nanoparticle and gastrointestinal exposures, and addressing occupational safety and health issues and concerns. This symposium overview article summarizes 5 talks that were presented at the 35th Annual meeting of the American College of Toxicology on the subject of “Applied Nanotechnology.” PMID:26957538

Comparative Toxicology of Libby Amphibole and Naturally Occurring Asbestos

EPA Science Inventory

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

Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies

PubMed Central

Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

2015-01-01

Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

PubMed

Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

2015-03-01

Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

Real Patient and its Virtual Twin: Application of Quantitative Systems Toxicology Modelling in the Cardiac Safety Assessment of Citalopram.

PubMed

Patel, Nikunjkumar; Wiśniowska, Barbara; Jamei, Masoud; Polak, Sebastian

2017-11-27

A quantitative systems toxicology (QST) model for citalopram was established to simulate, in silico, a 'virtual twin' of a real patient to predict the occurrence of cardiotoxic events previously reported in patients under various clinical conditions. The QST model considers the effects of citalopram and its most notable electrophysiologically active primary (desmethylcitalopram) and secondary (didesmethylcitalopram) metabolites, on cardiac electrophysiology. The in vitro cardiac ion channel current inhibition data was coupled with the biophysically detailed model of human cardiac electrophysiology to investigate the impact of (i) the inhibition of multiple ion currents (I Kr , I Ks , I CaL ); (ii) the inclusion of metabolites in the QST model; and (iii) unbound or total plasma as the operating drug concentration, in predicting clinically observed QT prolongation. The inclusion of multiple ion channel current inhibition and metabolites in the simulation with unbound plasma citalopram concentration provided the lowest prediction error. The predictive performance of the model was verified with three additional therapeutic and supra-therapeutic drug exposure clinical cases. The results indicate that considering only the hERG ion channel inhibition of only the parent drug is potentially misleading, and the inclusion of active metabolite data and the influence of other ion channel currents should be considered to improve the prediction of potential cardiac toxicity. Mechanistic modelling can help bridge the gaps existing in the quantitative translation from preclinical cardiac safety assessment to clinical toxicology. Moreover, this study shows that the QST models, in combination with appropriate drug and systems parameters, can pave the way towards personalised safety assessment.

Metabonomics: its potential as a tool in toxicology for safety assessment and data integration.

PubMed

Griffin, J L; Bollard, M E

2004-10-01

The functional genomic techniques of transcriptomics and proteomics promise unparalleled global information during the drug development process. However, if these technologies are used in isolation the large multivariate data sets produced are often difficult to interpret, and have the potential of missing key metabolic events (e.g. as a result of experimental noise in the system). To better understand the significance of these megavariate data the temporal changes in phenotype must be described. High resolution 1H NMR spectroscopy used in conjunction with pattern recognition provides one such tool for defining the dynamic phenotype of a cell, organ or organism in terms of a metabolic phenotype. In this review the benefits of this metabonomics/metabolomics approach to problems in toxicology will be discussed. One of the major benefits of this approach is its high throughput nature and cost effectiveness on a per sample basis. Using such a method the consortium for metabonomic toxicology (COMET) are currently investigating approximately 150 model liver and kidney toxins. This investigation will allow the generation of expert systems where liver and kidney toxicity can be predicted for model drug compounds, providing a new research tool in the field of drug metabolism. The review will also include how metabonomics may be used to investigate co-responses with transcripts and proteins involved in metabolism and stress responses, such as during drug induced fatty liver disease. By using data integration to combine metabolite analysis and gene expression profiling key perturbed metabolic pathways can be identified and used as a tool to investigate drug function.

Aquatic models, genomics and chemical risk management.

PubMed

Cheng, Keith C; Hinton, David E; Mattingly, Carolyn J; Planchart, Antonio

2012-01-01

The 5th Aquatic Animal Models for Human Disease meeting follows four previous meetings (Nairn et al., 2001; Schmale, 2004; Schmale et al., 2007; Hinton et al., 2009) in which advances in aquatic animal models for human disease research were reported, and community discussion of future direction was pursued. At this meeting, discussion at a workshop entitled Bioinformatics and Computational Biology with Web-based Resources (20 September 2010) led to an important conclusion: Aquatic model research using feral and experimental fish, in combination with web-based access to annotated anatomical atlases and toxicological databases, yields data that advance our understanding of human gene function, and can be used to facilitate environmental management and drug development. We propose here that the effects of genes and environment are best appreciated within an anatomical context - the specifically affected cells and organs in the whole animal. We envision the use of automated, whole-animal imaging at cellular resolution and computational morphometry facilitated by high-performance computing and automated entry into toxicological databases, as anchors for genetic and toxicological data, and as connectors between human and model system data. These principles should be applied to both laboratory and feral fish populations, which have been virtually irreplaceable sentinals for environmental contamination that results in human morbidity and mortality. We conclude that automation, database generation, and web-based accessibility, facilitated by genomic/transcriptomic data and high-performance and cloud computing, will potentiate the unique and potentially key roles that aquatic models play in advancing systems biology, drug development, and environmental risk management. Copyright © 2011 Elsevier Inc. All rights reserved.

Enhancing high throughput toxicology - development of putative adverse outcome pathways linking US EPA ToxCast screening targets to relevant apical hazards.

EPA Science Inventory

High throughput toxicology programs, such as ToxCast and Tox21, have provided biological effects data for thousands of chemicals at multiple concentrations. Compared to traditional, whole-organism approaches, high throughput assays are rapid and cost-effective, yet they generall...

Wildlife toxicology

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

Kendall, R.J.

1982-08-01

Wildlife toxicology may be defined as the study of the effects of environmental contaminants on wildlife species, as related to their wellbeing, general health, and reproduction. Results of studies with pesticides, heavy metals, and chlorinated hydrocarbons are examined. Integrated field and laboratory studies using selected model species might lead to ways of quantifying the adverse effects of chemical contaminants. (KRM)

A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time

DTIC Science & Technology

2015-06-01

J (2008) Health effects of exposure to vesicant agents. In: Chemical Warfare Agents – Chemistry , Pharmacology, Toxicology, and Therapeutics. Eds...sulfphide and the protective effect of flavonoids . Toxicology 69: 35-42. Wada S, Nishimoto Y, Miyanishi M, Kambe S, Miller R W(1968) Mustard gas as

Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows

USDA-ARS?s Scientific Manuscript database

17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the li...

Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats.

PubMed

Iannone, Michelangelo; Bulotta, Stefania; Paolino, Donatella; Zito, Maria Cristina; Gratteri, Santo; Costanzo, Francesco S; Rotiroti, Domenicantonio

2006-02-16

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.

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.

The impact of substance abuse on mortality in patients with severe traumatic brain injury.

PubMed

O'Phelan, Kristine; McArthur, David L; Chang, Cherylee W J; Green, Deborah; Hovda, David A

2008-09-01

Drug and alcohol use are common in neurotrauma patients. Despite growing methamphetamine use there are few studies of the impact of methamphetamine use on outcome after traumatic brain injury (TBI). We conducted a retrospective review of 5-years of data from a trauma database. Inclusion criteria included severe TBI and diagnosis codes indicating head injury. The entire database was analyzed and then a subset of patients with complete toxicology data were examined separately. Primary outcome was mortality. Four hundred eighty-three patients were included. Toxicology results were available for 52.6% of patients. Alcohol, amphetamines, and cannabis were the most commonly detected substances. Overall mortality was 50.9%. When the group with complete tox screen data were analyzed, a toxicology screen that was positive for alcohol or amphetamine was associated with decreased mortality with an odds ratio of 0.23 (CI: 0.10-0.56, p = 0.001) and 0.25 (CI: 0.08-0.79, p = 0.02), respectively. When the subset of patients for whom toxicology data were available was analyzed the amphetamine-positive group was more likely to use cannabis and less likely to use alcohol. We unexpectedly found alcohol and methamphetamine use to be associated with decreased mortality. Neurotoxic and possible neuroprotective mechanisms of these substances are discussed as well as possible interactions between cannabis and methamphetamine. The potential influence of psycho-social factors are also considered. Prospective studies are needed to further investigate the effects of drug and alcohol use on outcome after severe TBI.

A framework for in vitro systems toxicology assessment of e-liquids

PubMed Central

Iskandar, Anita R.; Gonzalez-Suarez, Ignacio; Majeed, Shoaib; Marescotti, Diego; Sewer, Alain; Xiang, Yang; Leroy, Patrice; Guedj, Emmanuel; Mathis, Carole; Schaller, Jean-Pierre; Vanscheeuwijck, Patrick; Frentzel, Stefan; Martin, Florian; Ivanov, Nikolai V.; Peitsch, Manuel C.; Hoeng, Julia

2016-01-01

Abstract Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are the most recognized prototype, have been quickly gaining ground on conventional cigarettes because they are perceived as less harmful. Research assessing the potential effects of ENDS exposure in humans is currently limited and inconclusive. New products are emerging with numerous variations in designs and performance parameters within and across brands. Acknowledging these challenges, we present here a proposed framework for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery of assays for standard toxicity assessments. The proposed framework utilizes high-throughput toxicity assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and a systems-level investigation of the cellular mechanisms of toxicity is an integral part. An analytical chemistry investigation is also included as a part of the framework to provide accurate and reliable chemistry data solidifying the toxicological assessment. In its simplest form, the framework comprises of three main layers: (1) high-throughput toxicity screening of e-liquids using primary human cell culture systems; (2) toxicity-related mechanistic assessment of selected e-liquids, and (3) toxicity-related mechanistic assessment of their aerosols using organotypic air–liquid interface airway culture systems. A systems toxicology assessment approach is leveraged to enable in-depth analyses of the toxicity-related cellular mechanisms of e-liquids and their aerosols. We present example use cases to demonstrate the suitability of the framework for a robust in vitro assessment of e-liquids and their aerosols. PMID:27117495

A framework for in vitro systems toxicology assessment of e-liquids.

PubMed

Iskandar, Anita R; Gonzalez-Suarez, Ignacio; Majeed, Shoaib; Marescotti, Diego; Sewer, Alain; Xiang, Yang; Leroy, Patrice; Guedj, Emmanuel; Mathis, Carole; Schaller, Jean-Pierre; Vanscheeuwijck, Patrick; Frentzel, Stefan; Martin, Florian; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

2016-07-01

Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are the most recognized prototype, have been quickly gaining ground on conventional cigarettes because they are perceived as less harmful. Research assessing the potential effects of ENDS exposure in humans is currently limited and inconclusive. New products are emerging with numerous variations in designs and performance parameters within and across brands. Acknowledging these challenges, we present here a proposed framework for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery of assays for standard toxicity assessments. The proposed framework utilizes high-throughput toxicity assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and a systems-level investigation of the cellular mechanisms of toxicity is an integral part. An analytical chemistry investigation is also included as a part of the framework to provide accurate and reliable chemistry data solidifying the toxicological assessment. In its simplest form, the framework comprises of three main layers: (1) high-throughput toxicity screening of e-liquids using primary human cell culture systems; (2) toxicity-related mechanistic assessment of selected e-liquids, and (3) toxicity-related mechanistic assessment of their aerosols using organotypic air-liquid interface airway culture systems. A systems toxicology assessment approach is leveraged to enable in-depth analyses of the toxicity-related cellular mechanisms of e-liquids and their aerosols. We present example use cases to demonstrate the suitability of the framework for a robust in vitro assessment of e-liquids and their aerosols.

Food for Thought … Integrated Testing Strategies for Safety Assessments

PubMed Central

Hartung, Thomas; Luechtefeld, Tom; Maertens, Alexandra; Kleensang, Andre

2013-01-01

Summary Despite the fact that toxicology uses many stand-alone tests, a systematic combination of several information sources very often is required: Examples include: when not all possible outcomes of interest (e.g., modes of action), classes of test substances (applicability domains), or severity classes of effect are covered in a single test; when the positive test result is rare (low prevalence leading to excessive false-positive results); when the gold standard test is too costly or uses too many animals, creating a need for prioritization by screening. Similarly, tests are combined when the human predictivity of a single test is not satisfactory or when existing data and evidence from various tests will be integrated. Increasingly, kinetic information also will be integrated to make an in vivo extrapolation from in vitro data. Integrated Testing Strategies (ITS) offer the solution to these problems. ITS have been discussed for more than a decade, and some attempts have been made in test guidance for regulations. Despite their obvious potential for revamping regulatory toxicology, however, we still have little guidance on the composition, validation, and adaptation of ITS for different purposes. Similarly, Weight of Evidence and Evidence-based Toxicology approaches require different pieces of evidence and test data to be weighed and combined. ITS also represent the logical way of combining pathway-based tests, as suggested in Toxicology for the 21st Century. This paper describes the state of the art of ITS and makes suggestions as to the definition, systematic combination, and quality assurance of ITS. PMID:23338803

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.

Locally Weighted Learning Methods for Predicting Dose-Dependent Toxicity with Application to the Human Maximum Recommended Daily Dose

DTIC Science & Technology

2012-09-10

Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland 21702, United States ABSTRACT: Toxicological ...species. Thus, it is more advantageous to predict the toxicological effects of a compound on humans directly from the human toxicological data of related...compounds. However, many popular quantitative structure−activity relationship ( QSAR ) methods that build a single global model by fitting all training

Identification and Optimization of Classifier Genes from Multi-Class Earthworm Microarray Dataset

DTIC Science & Technology

2010-10-28

rapid and accurate diagnostic assays. A variety of toxicological effects have been associated with explosive compounds TNT and RDX. One important goal of...analyze toxicological mechanisms for two military- unique explosive compounds 2,4,6-trinitrotolune (TNT) and 1,3,5- trinitro-1,3,5-triazacyclohexane...also known as Royal Demolition eXplosive or RDX) [7,8]. These two compounds exhibit distinctive toxicological properties that are accompanied by

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.

Mammalian Toxicology Testing: Problem Definition Study. Part 1. Comparative Analysis Report.

DTIC Science & Technology

1981-03-01

Requirements continued- 20. AfT’AC? (CaEtas roWm W SM N tw@"W 41011 iadnit y Slock nmanner) >Global Army mammalian toxicology testing requirements were...for viewing the Army’s toxico - logical requirements which takes into account the materiel requirements itself, changes in requirements over the...Almost 1,700 chemicals were estimated Lo be in the Research, Development, Test & Engineering cycle, 200 weapons were found to potentially represent

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.

Elucidating Cannabinoid Biology in Zebrafish (Danio rerio)

PubMed Central

Krug, Randall G.; Clark, Karl J.

2015-01-01

The number of annual cannabinoid users exceeds 100,000,000 globally and an estimated 9 % of these individuals will suffer from dependency. Although exogenous cannabinoids, like those contained in marijuana, are known to exert their effects by disrupting the endocannabinoid system, a dearth of knowledge exists about the potential toxicological consequences on public health. Conversely, the endocannabinoid system represents a promising therapeutic target for a plethora of disorders because it functions to endogenously regulate a vast repertoire of physiological functions. Accordingly, the rapidly expanding field of cannabinoid biology has sought to leverage model organisms in order to provide both toxicological and therapeutic insights about altered endocannabinoid signaling. The primary goal of this manuscript is to review the existing field of cannabinoid research in the genetically tractable zebrafish model—focusing on the cannabinoid receptor genes, cnr1 and cnr2, and the genes that produce enzymes for synthesis and degradation of the cognate ligands anandamide and 2-arachidonylglycerol. Consideration is also given to research that has studied the effects of exposure to exogenous phytocannabinoids and synthetic cannabinoids that are known to interact with cannabinoid receptors. These results are considered in the context of either endocannabinoid gene expression or endocannabinoid gene function, and are integrated with findings from rodent studies. This provides the framework for a discussion of how zebrafish may be leveraged in the future to provide novel toxicological and therapeutic insights in the field of cannabinoid biology, which has become increasingly significant given recent trends in cannabis legislation. PMID:26192460

Human Health Effects of Trichloroethylene: Key Findings and Scientific Issues

PubMed Central

Jinot, Jennifer; Scott, Cheryl Siegel; Makris, Susan L.; Cooper, Glinda S.; Dzubow, Rebecca C.; Bale, Ambuja S.; Evans, Marina V.; Guyton, Kathryn Z.; Keshava, Nagalakshmi; Lipscomb, John C.; Barone, Stanley; Fox, John F.; Gwinn, Maureen R.; Schaum, John; Caldwell, Jane C.

2012-01-01

Background: In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed a toxicological review of trichloroethylene (TCE) in September 2011, which was the result of an effort spanning > 20 years. Objectives: We summarized the key findings and scientific issues regarding the human health effects of TCE in the U.S. EPA’s toxicological review. Methods: In this assessment we synthesized and characterized thousands of epidemiologic, experimental animal, and mechanistic studies, and addressed several key scientific issues through modeling of TCE toxicokinetics, meta-analyses of epidemiologic studies, and analyses of mechanistic data. Discussion: Toxicokinetic modeling aided in characterizing the toxicological role of the complex metabolism and multiple metabolites of TCE. Meta-analyses of the epidemiologic data strongly supported the conclusions that TCE causes kidney cancer in humans and that TCE may also cause liver cancer and non-Hodgkin lymphoma. Mechanistic analyses support a key role for mutagenicity in TCE-induced kidney carcinogenicity. Recent evidence from studies in both humans and experimental animals point to the involvement of TCE exposure in autoimmune disease and hypersensitivity. Recent avian and in vitro mechanistic studies provided biological plausibility that TCE plays a role in developmental cardiac toxicity, the subject of substantial debate due to mixed results from epidemiologic and rodent studies. Conclusions: TCE is carcinogenic to humans by all routes of exposure and poses a potential human health hazard for noncancer toxicity to the central nervous system, kidney, liver, immune system, male reproductive system, and the developing embryo/fetus. PMID:23249866

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

Toxicology of Biodiesel Combustion products

EPA Science Inventory

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

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

Overview of ToxCast™ | Science Inventory | US EPA

EPA Pesticide Factsheets

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

Consideration of interaction between nanoparticles and food components for the safety assessment of nanoparticles following oral exposure: A review.

PubMed

Cao, Yi; Li, Juan; Liu, Fang; Li, Xiyue; Jiang, Qin; Cheng, Shanshan; Gu, Yuxiu

2016-09-01

Nanoparticles (NPs) are increasingly used in food, and the toxicity of NPs following oral exposure should be carefully assessed to ensure the safety. Indeed, a number of studies have shown that oral exposure to NPs, especially solid NPs, may induce toxicological responses both in vivo and in vitro. However, most of the toxicological studies only used NPs for oral exposure, and the potential interaction between NPs and food components in real life was ignored. In this review, we summarized the relevant studies and suggested that the interaction between NPs and food components may exist by that 1) NPs directly affect nutrients absorption through disruption of microvilli or alteration in expression of nutrient transporter genes; 2) food components directly affect NP absorption through physico-chemical modification; 3) the presence of food components affect oxidative stress induced by NPs. All of these interactions may eventually enhance or reduce the toxicological responses induced by NPs following oral exposure. Studies only using NPs for oral exposure may therefore lead to misinterpretation and underestimation/overestimation of toxicity of NPs, and it is necessary to assess the synergistic effects of NPs in a complex system when considering the safety of NPs used in food. Copyright © 2016 Elsevier B.V. All rights reserved.

RNA interference: Applications and advances in insect toxicology and insect pest management.

PubMed

Kim, Young Ho; Soumaila Issa, Moustapha; Cooper, Anastasia M W; Zhu, Kun Yan

2015-05-01

Since its discovery, RNA interference (RNAi) has revolutionized functional genomic studies due to its sequence-specific nature of post-transcriptional gene silencing. In this paper, we provide a comprehensive review of the recent literature and summarize the current knowledge and advances in the applications of RNAi technologies in the field of insect toxicology and insect pest management. Many recent studies have focused on identification and validation of the genes encoding insecticide target proteins, such as acetylcholinesterases, ion channels, Bacillus thuringiensis receptors, and other receptors in the nervous system. RNAi technologies have also been widely applied to reveal the role of genes encoding cytochrome P450 monooxygenases, carboxylesterases, and glutathione S-transferases in insecticide detoxification and resistance. More recently, studies have focused on understanding the mechanism of insecticide-mediated up-regulation of detoxification genes in insects. As RNAi has already shown great potentials for insect pest management, many recent studies have also focused on host-induced gene silencing, in which several RNAi-based transgenic plants have been developed and tested as proof of concept for insect pest management. These studies indicate that RNAi is a valuable tool to address various fundamental questions in insect toxicology and may soon become an effective strategy for insect pest management. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessment of Environmental and Occupational Health Impacts in Munitions and Weapon Systems Development: A Phased Approach

DTIC Science & Technology

2010-12-01

Human Health Impacts of New Energetic Compounds. • Models – QSARs • In vitro toxicology • In vivo toxicology • Aligned with RDT&E level of...D.A.B.T. Health Effects Research Program Directorate of Toxicology Army Institute of Public Health UNCLASSIFIED Report Documentation Page Form...program. Early in the research stage models are primarily relied upon (e.g. QSAR approaches) and as the technology progresses, a greater reliance is

Toxicological evaluation of Cd-based fluorescent nanoprobes by means of in vivo studies

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Ma-Hock, Lan; Landsiedel, Robert; van Ravenzwaay, Bennard

2018-02-01

Cadmium still represents a stigma for many research- and/or industrial applications. Some deleterious effects are attributed to Cadmium. In the present work, highly fluorescent Cadmium sulfide quantum dots are investigated by e.g. physical-chemical characterization. Most important however is their application as fluorescent probes for bio-imaging in living cells and tissues. This work presents their toxicological evaluation by means of in vivo studies. Bio-imaging experiments are performed without any pre-treatment. The toxicological studies performed, strongly indicate that the use of Cadmium based nanoparticles as fluorescent probes may be nonhazardous and not induce side effects for cells/tissues.

NONYLPHENOL AND ATRAZINE INDUCE INVERSE EFFECTS ON MAMMARY GLAND DEVELOPMENT IN FEMALE RATS EXPOSED IN UTERO

EPA Science Inventory

Nonylphenol and Atrazine Induce Inverse Effects on Mammary Gland Development in Female Rats Exposed In Utero.
HJ Moon1, SY Han1, CC Davis2, and SE Fenton2
1 Department of Toxicology, NITR, Korea FDA, 5Nokbun-Dong, Eunpyung-Gu, Seoul, Korea and 2 Reproductive Toxicology Divi...

PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS

EPA Science Inventory

PREGNANCY LOSS IN THE F344 RAT CAUSED BY BROMODICHLOROMETHANE: EFFECTS ON SERUM LUTEINIZING HORMONE LEVELS
Bielmeier1, S.R., D.S. Best2, and M.G. Narotsky2; 1University of North Carolina at Chapel Hill, Curriculum in Toxicology, 2Reproductive Toxicology Division, U.S. Enviro...

Reproductive Toxicology Testing with EDCS

EPA Science Inventory

An introduction to reproductive toxicology: the basic approaches to testing chemicals for adverse effects using multigenerational studies with rats and how the regulatory agencies used the data in risk assessments. Case studies were presented of how endocrine or genomic data were...

DNA ARRAYS: TECHNOLOGY, OPTIONS AND TOXOCOLOGICAL APPLICATIONS

EPA Science Inventory

DNA arrays: technology, options and toxicological applications.

Rockett JC, Dix DJ.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, NC 27711, USA. rockett.john@epa.gov

The hu...

BIOMARKERS OF EXPOSURE, EFFECT AND SUSCEPTIBILITY IN FISHES

EPA Science Inventory

Understanding basic mechanisms of toxicological processes is integral to assessment of risk, In aquatic toxicology, however, the mechanistic evaluation of environmental chemicals is a much younger area of investigation than in mammalian systems and only recently has received sig...

Evaporation control research, 1955-58

USGS Publications Warehouse

Cruse, Robert R.; Harbeck, Guy Earl

1960-01-01

One hundred fifty-two compounds and compositions of matter were screened as potential evaporation retardants. The homologous straight-chain fatty alkanols are considered the best materials for retardants. Several methods of application of the alkanols to the reservoir surface were investigated. Although wick-type drippers for the application of liquids and cage rafts for the application of solids appear to be the most promising methods from an economic standpoint, both methods have serious disadvantages. Considerable study was given to reducing biochemical oxidation of the evaporation retardants. Copper in several forms was found adequate as a bacteriostatic agent but posed a potential hazard because of its toxicity. Many other bactericides that were tested were also toxic. Two sets of large-scale field tests have been completed and several others are still in progress. On the larger reservoirs, the reduction of evaporation was not more than 20 percent under the prevailing conditions and the application procedure used. Three major practical problems remain; namely, the effects and action of wind on the monofilm, the effects of biochemical oxidation, and the most effective method of application. Fundamental problems remaining include the effects of various impurities, and the composition of the best evaporation retardant; the long-range effects of monofilms on the limnology of a reservoir, including the transfer of oxygen and carbon dioxide; toxicological aspects of all components of any evaporation-retardant composition, plus toxicology of any composition chosen for large-scale use; and further studies of the calorimetry and thermodynamics involved in the mechanism of evaporation and its reduction by a monofilm.

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.

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

PubMed

Leone, Stefania; Di Cianni, Simone; Casati, Andrea; Fanelli, Guido

2008-08-01

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Laboratory for Energy-Related Health Research: Annual report, fiscal year 1987

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

Abell, D.L.

1989-04-01

The laboratory's research objective is to provide new knowledge for an improved understanding of the potential bioenvironmental and occupational health problems associated with energy utilization. Our purpose is to contribute to the safe and healthful development of energy resources for the benefit of mankind. This research encompasses several areas of basic investigation that relate to toxicological and biomedical problems associated with potentially toxic chemical and radioactive substances and ionizing radiation, with particular emphasis on carcinogenicity. Studies of systemic injury and nuclear-medical diagnostic and therapeutic methods are also involved. This program is interdisciplinary; it involves physics, chemistry, environmental engineering, biophysics andmore » biochemistry, cellular and molecular biology, physiology, immunology, toxicology, both human and veterinary medicine, nuclear medicine, pathology, hematology, radiation biology, reproductive biology, oncology, biomathematics, and computer science. The principal themes of the research at LEHR center around the biology, radiobiology, and health status of the skeleton and its blood-forming constituents; the toxicology and properties of airborne materials; the beagle as an experimental animal model; carcinogenesis; and the scaling of the results from laboratory animal studies to man for appropriate assessment of risk.« less

Problem Definition Studies on Potential Environmental Pollutants. 4. Physical, Chemical, Toxicological, and Biological Properties of Benzene; Toluene; Xylenes; and para-Chlorophenyl Methyl Sulfide, Sulfoxide, and Sulfone

DTIC Science & Technology

1976-06-01

ecological hazards of benzene, toluene, xylenes,* and p-chlorophenyl methyl sulfide, sulfoxide, and sulfone at Rocky Mountain Arsenal (RMA). That assessment...recently reviewed the occupational hazard associated with the use of benzene, toluene, and xylene and has recomiended the folcwln !.ImitS In workroom air...Toxicology and Ecological Hazards of "Venzene; Toluene; Xylenes; and p-Chlorophenyl Methyl Sulfide, Sulfoxide, and Sulfone at Rocky tc-cntain Arsenal

The pharmacology and toxicology of three new biologic agents used in pulmonary medicine.

PubMed

Albertson, T E; Walby, W F; Allen, R P; Tharratt, R S

1995-01-01

Biological agents have played an important role in the evolution of modern medical therapeutics. Recent advances in biologicals have in part been stimulated by the biotechnology revolution seen over the last several years. Toxicologists need to be aware of the proposed mechanisms and approved and experimental uses of these new biologic agents. Further, controversies about their use, efficacy, cost issues and potential toxicities should be known. Often these drugs are designed for small patient populations thus limiting the availability of human toxicological data bases. This paper reviews the pharmacology and toxicology of three new biologics (recombinant human DNase I, alpha 1-protease inhibitor, and nitric oxide). These agents appear to have important roles in treating specific diseases or disease states seen in pulmonary medicine.

Nanomaterial synthesis and characterization for toxicological studies: TiO2 case study

USGS Publications Warehouse

Valsami-Jones, E.; Berhanu, D.; Dybowska, A.; Misra, S.; Boccaccini, A.R.; Tetley, T.D.; Luoma, S.N.; Plant, J.A.

2008-01-01

In recent years it has become apparent that the novel properties of nanomaterials may predispose them to a hitherto unknown potential for toxicity. A number of recent toxicological studies of nanomaterials exist, but these appear to be fragmented and often contradictory. Such discrepancies may be, at least in part, due to poor description of the nanomaterial or incomplete characterization, including failure to recognise impurities, surface modifications or other important physicochemical aspects of the nanomaterial. Here we make a case for the importance of good quality, well-characterized nanomaterials for future toxicological studies, combined with reliable synthesis protocols, and we present our efforts to generate such materials. The model system for which we present results is TiO2 nanoparticles, currently used in a variety of commercial products. ?? 2008 The Mineralogical Society.

Genetic toxicology of lysergic acid diethylamide (LSD-25).

PubMed

Cohen, M M; Shiloh, Y

The acute and the chronic psychotomimetic potentials of the hallucinogen lysergic acid diethylamide (LSD-25) have been recognized for almost 40 years. That additional types of the biological effects should have come under scrutiny was directly attributable to widespread use and abuse of this drug on a world-wide basis. Although "genetic toxicology" encompasses a broad spectrum of disciplines, including many areas of highly specialized research, perhaps the most germane, and those on which this review has concentrated, are Clastogenicity, Mutagenicity, Teratogenicity and Oncogenicity. Based on our current understanding and interpretation of the available data, the genetic toxicology of LSD provides an excellent example of Newton's "third law of motion", e.g., to every force there is an equal and opposite reaction force. From the published material it is impossible to draw clear cut conclusions regarding any of the above "problem areas" in spite of the considerable scientific effort invested. Most of the in vitro studies performed on the clastogenicity of LSD indicate either suppression of mitosis or enhanced chromosome damage. However, extrapolation of such results to the in vivo situation is very difficult. With regard to in vivo human use of the drug, no concensus is attainable as to chromosome breakage and the inconsistencies within and between studies remain inexplicable. However, several of the "controlled" investigations assessing the in vivo effect of chemically pure LSD suggest a transient increase in lymphocyte chromosome breakage. On the other hand, the results of cytogenetic studies on experimental animals are contradictory. Although human studies are nonexistent, in those experimental organisms tested, using accepted techniques, LSD proved to be, at best, a weak mutagen, if mutagenic at all. Teratogenicity studies in animals are confusing due to the multitude of organisms and plethora of discriminant parameters studied. However, with regard to man there has been ample opportunity and one can conclude that LSD is not teratogenic. As to the drug's oncogenic potential, the 3 reported cases of leukemia in LSD users are most likely the result of coincidence.

Chemical mixtures in potable water in the U.S.

USGS Publications Warehouse

Ryker, Sarah J.

2014-01-01

In recent years, regulators have devoted increasing attention to health risks from exposure to multiple chemicals. In 1996, the US Congress directed the US Environmental Protection Agency (EPA) to study mixtures of chemicals in drinking water, with a particular focus on potential interactions affecting chemicals' joint toxicity. The task is complicated by the number of possible mixtures in drinking water and lack of toxicological data for combinations of chemicals. As one step toward risk assessment and regulation of mixtures, the EPA and the Agency for Toxic Substances and Disease Registry (ATSDR) have proposed to estimate mixtures' toxicity based on the interactions of individual component chemicals. This approach permits the use of existing toxicological data on individual chemicals, but still requires additional information on interactions between chemicals and environmental data on the public's exposure to combinations of chemicals. Large compilations of water-quality data have recently become available from federal and state agencies. This chapter demonstrates the use of these environmental data, in combination with the available toxicological data, to explore scenarios for mixture toxicity and develop priorities for future research and regulation. Occurrence data on binary and ternary mixtures of arsenic, cadmium, and manganese are used to parameterize the EPA and ATSDR models for each drinking water source in the dataset. The models' outputs are then mapped at county scale to illustrate the implications of the proposed models for risk assessment and rulemaking. For example, according to the EPA's interaction model, the levels of arsenic and cadmium found in US groundwater are unlikely to have synergistic cardiovascular effects in most areas of the country, but the same mixture's potential for synergistic neurological effects merits further study. Similar analysis could, in future, be used to explore the implications of alternative risk models for the toxicity and interaction of complex mixtures, and to identify the communities with the highest and lowest expected value for regulation of chemical mixtures.

MODELING CHEMICAL FATE AND METABOLISM FOR COMPUTATIONAL TOXICOLOGY

EPA Science Inventory

The goal of ORD's Computational Toxicology initiative is to develop the science for EPA to prioritize toxicity-testing requirements for chemicals subject to regulation. Many toxic effects, however, result from metabolism of parent chemicals to form metabolites that are much more...

Approach for environmental baseline water sampling

USGS Publications Warehouse

Smith, K.S.

2011-01-01

Samples collected during the exploration phase of mining represent baseline conditions at the site. As such, they can be very important in forecasting potential environmental impacts should mining proceed, and can become measurements against which future changes are compared. Constituents in stream water draining mined and mineralized areas tend to be geochemically, spatially, and temporally variable, which presents challenges in collecting both exploration and baseline water-quality samples. Because short-term (daily) variations can complicate long-term trends, it is important to consider recent findings concerning geochemical variability of stream-water constituents at short-term timescales in designing sampling plans. Also, adequate water-quality information is key to forecasting potential ecological impacts from mining. Therefore, it is useful to collect baseline water samples adequate tor geochemical and toxicological modeling. This requires complete chemical analyses of dissolved constituents that include major and minor chemical elements as well as physicochemical properties (including pH, specific conductance, dissolved oxygen) and dissolved organic carbon. Applying chemical-equilibrium and appropriate toxicological models to water-quality information leads to an understanding of the speciation, transport, sequestration, bioavailability, and aquatic toxicity of potential contaminants. Insights gained from geochemical and toxicological modeling of water-quality data can be used to design appropriate mitigation and for economic planning for future mining activities.

Molecular Mechanisms of Action of BPA.

PubMed

Acconcia, Filippo; Pallottini, Valentina; Marino, Maria

2015-01-01

Bisphenol A (BPA) exposure has been associated with serious endocrine-disrupting effects in humans and wildlife. Toxicological and epidemiological studies evidenced that BPA increases body mass index and disrupts normal cardiovascular physiology by interfering with endogenous hormones in rodents, nonhuman primates, and cell culture test systems. The BPA concentration derived from these experiments were used by government regulatory agencies to determine the safe exposure levels of BPA in humans. However, accumulating literature in vivo and in vitro indicate that at concentrations lower than that reported in toxicological studies, BPA could elicit a different endocrine-disrupting capacity. To further complicate this picture, BPA effects rely on several and diverse mechanisms that converge upon endocrine and reproductive systems. If all or just few of these mechanisms concur to the endocrine-disrupting potential of low doses of BPA is at present still unclear. Thus, taking into account that the incidence and/or prevalence of health problems associated with endocrine disruption have increased worldwide, the goal of the present review is to give an overview of the many mechanisms of BPA action in order to decipher whether different mechanisms are at the root of the effect of low dose of BPA on endocrine system.

Safety pharmacology — Current and emerging concepts

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

Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor

2013-12-01

Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combiningmore » toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.« less

Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats.

PubMed

Mellado-García, P; Puerto, M; Pichardo, S; Llana-Ruiz-Cabello, M; Moyano, R; Blanco, A; Jos, A; Cameán, A M

2016-04-01

Proallium AP(®) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP(®) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed-adverse-effect-level (NOAEL) for Proallium AP(®) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports.

PubMed

Mei, Nan; Guo, Xiaoqing; Ren, Zhen; Kobayashi, Daisuke; Wada, Keiji; Guo, Lei

2017-01-02

Ginkgo biloba seeds and leaves have been used as a traditional herbal remedy for thousands of years, and its leaf extract has been consumed as a botanical dietary supplement for decades. Ginkgo biloba extract is a complex mixture with numerous components, including flavonol glycosides and terpene lactones, and is one of the most widely sold botanical dietary supplements worldwide. Concerns about potential health risks for the general population have been raised because of the widespread human exposure to Ginkgo biloba and its potential toxic and carcinogenic activities in rodents. The National Toxicology Program conducted 2-year gavage studies on one Ginkgo biloba leaf extract and concluded that there was clear evidence of carcinogenic activity of this extract in mice based on an increased incidence of hepatocellular carcinoma and hepatoblastoma. Recently, Ginkgo biloba leaf extract has been classified as a possible human carcinogen (Group 2B) by the International Agency for Research on Cancer. This review presents updated information on the toxicological effects from experimental studies both in vitro and in vivo to human case reports (caused by ginkgo seeds or leaves), and also summarizes the negative results from relatively large clinical trials.

23 years of toxicology testing fatally injured pilots: Implications for aviation and other modes of transportation.

PubMed

McKay, Mary Pat; Groff, Loren

2016-05-01

Use of over-the-counter, prescription, and illicit drugs is increasing in the United States (US). Many of these drugs are psychoactive and can affect the user's ability to safely operate a vehicle. However, data about drug use by vehicle operators is typically limited to a small proportion of operators and a short list of drugs. For instance, required testing for commercial vehicle operators following most accidents is limited to a urine test for 11 drugs. By comparison, the Federal Aviation Administration (FAA), routinely tests fatally injured pilots' blood and tissues for hundreds of compounds. This study used the results from these tests to assess drug use in aviation. Using matched data from the FAA's Civil Aerospace Medical Institute toxicology database and the National Transportation Safety Board's (NTSB's) aviation accident database, this study examined trends in the prevalence of over-the-counter, prescription, and illicit drugs identified in toxicology tests of fatally injured pilots between 1990 and 2012. Cases that failed to match or where toxicology testing had not been performed were excluded. Pilots identified by the NTSB investigation as being the "flying pilot" at the time of the accident and results from blood or tissues were included. Toxicology results for ethanol and other alcohols were not included. Positive test results were categorized by drug type and potential for causing impairment. Analysis used SPSS Version 19.1 to perform linear by linear chi-squared statistics. The study included 6677 pilots or 87% of the eligible subjects. The large majority were male (98%) and flying general aviation operations (96%) at the time of their fatal accident. There were increasing trends in pilots' use of all drugs, potentially impairing drugs, drugs used to treat potentially impairing conditions, drugs designated as controlled substances, and illicit drugs. The most common potentially impairing drug pilots had used was diphenhydramine, a sedating antihistamine that is an active ingredient in many over-the-counter allergy formulations, cold medicines, and sleep aids in the US. Although evidence of illicit drug use was found only in a small number of cases, the percentage of pilots testing positive for marijuana use increased during the study period, mostly in the last 10 years. Published by Elsevier Ltd.

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.

Developmental toxicology: adequacy of current methods.

PubMed

Peters, P W

1998-01-01

Toxicology embraces several disciplines such as carcinogenicity, mutagenicity and reproductive toxicity. Reproductive toxicology is concerned with possible effects of substances on the reproductive process, i.e. on sexual organs and their functions, endocrine regulation, fertilization, transport of the fertilized ovum, implantation, and embryonic, fetal and postnatal development, until the end-differentiation of the organs is achieved. Reproductive toxicology is divided into areas related to male and female fertility, and developmental toxicology. Developmental toxicology can be further broken down into prenatal and postnatal toxicology. Today, much new information is available about the origins of developmental disorders resulting from chemical exposure. While these findings seem to promise important new developments in methodology and research, there is a danger of losing sight of the precepts and principles established in the light of existing knowledge. There is also a danger that we may fail to correct shortcomings in our existing procedures and practice. The aim of this presentation is to emphasize the importance of testing substances for their impact in advance of their use and to underline that we must use the best existing tools for carrying out risk assessments. Moreover, it needs to be stressed that there are many substances that are never assessed with respect to reproductive and developmental toxicity. Similarly, our programmes for post-marketing surveillance with respect to developmental toxicology are grossly inadequate. Our ability to identify risks to normal development and reproduction would be much improved, first if a number of straightforward precepts were always followed and second, if we had a clearer understanding of what we mean by risk and acceptable levels of risk in the context of development. Other aims of this paper are: to stress the complexity of the different stages of normal prenatal development; to note the principles that are applicable in developmental and especially prenatal toxicology; to describe the different agents that might act as developmental toxicants or teratogens; to show the broad scope of different effects caused by developmental toxic agents; and to indicate methods to detect and to recognise causes of developmental defects with the primary objective of preventing these disorders.

Chemical fate and biological effects of several endocrine disrupters compounds in two echinoderm species.

PubMed

Sugni, Michela; Tremolada, Paolo; Porte, Cinta; Barbaglio, Alice; Bonasoro, Francesco; Carnevali, M Daniela Candia

2010-03-01

Two echinoderm species, the sea urchin Paracentrotus lividus and the feather star Antedon mediterranea, were exposed for 28 days to several EDCs: three putative androgenic compounds, triphenyltin (TPT), fenarimol (FEN), methyltestosterone (MET), and two putative antiandrogenic compounds, p,p'-DDE (DDE) and cyproterone acetate (CPA). The exposure nominal concentrations were from 10 to 3000 ng L(-1), depending on the compound. This paper is an attempt to join three different aspects coming from our ecotoxicological tests: (1) the chemical behaviour inside the experimental system; (2) the measured toxicological endpoints; (3) the biochemical responses, to which the measured endpoints may depend. The chemical fate of the different compounds was enquired by a modelling approach throughout the application of the 'Aquarium model'. An estimation of the day-to-day concentration levels in water and biota were obtained together with the amount assumed each day by each animal (uptake in microg animal(-1) d(-1) or ng g-wet weight(-1) d(-1)). The toxicological endpoints investigated deal with the reproductive potential (gonad maturation stage, gonad index and oocyte diameter) and with the regenerative potential (growth and histology). Almost all the compounds exerted some kind of effect at the tested concentrations, however TPT was the most effective in altering both reproductive and regenerative parameters (also at the concentration of few ng L(-1)). The biochemical analyses of testosterone (T) and 17beta-estradiol (E(2)) also showed the ability of the selected compounds to significantly alter endogenous steroid concentrations.

From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

PubMed

Choudhuri, Supratim; Patton, Geoffrey W; Chanderbhan, Ronald F; Mattia, Antonia; Klaassen, Curtis D

2018-01-01

Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of "omics" (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30-40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

Toxicological effects of pyrethroids on non-target aquatic insects.

PubMed

Antwi, Frank B; Reddy, Gadi V P

2015-11-01

The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Titanium dioxide: inhalation toxicology and epidemiology.

PubMed

Hext, Paul M; Tomenson, John A; Thompson, Peter

2005-08-01

Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect across both TiO(2) types. The epidemiological investigations evaluated the mortality statistics at 11 European and 4 US TiO(2) manufacturing plants. They concluded that there was no suggestion of any carcinogenic effect associated with workplace exposure to TiO(2).

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.

Methods used to characterize the chemical composition and biological activity of environmental waters throughout the United States, 2012-14

USGS Publications Warehouse

Romanok, Kristin M.; Reilly, Timothy J.; Barber, Larry B.; Boone, J. Scott; Buxton, Herbert T.; Foreman, William T.; Furlong, Edward T.; Hladik, Michelle; Iwanowicz, Luke R.; Journey, Celeste A.; Kolpin, Dana W.; Kuivila, Kathryn; Loftin, Keith A.; Mills, Marc A.; Meyer, Michael T.; Orlando, James L.; Smalling, Kelly L.; Villeneuve, Daniel L.; Bradley, Paul M.

2017-03-22

A vast array of chemical compounds are in wide commercial use in the United States, and the potential ecological and human-health effect of exposure to chemical mixtures has been identified as a high priority in environment health science. Awareness of the potential effects of low-level chemical exposures is rising. The U.S. Geological Survey, in cooperation with the U.S. Environmental Protection Agency, conducted a study in which samples were collected from 38 streams in 25 States to provide an overview of contaminants found in stream water across the Nation. Additionally, biological screening assays were used to help determine any potential ecological and human-health effects of these chemical mixtures and to prioritize target chemicals for future toxicological studies. This report describes the site locations and the sampling and analytical methods and quality-assurance procedures used in the study.

Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats

PubMed Central

Iannone, Michelangelo; Bulotta, Stefania; Paolino, Donatella; Zito, Maria Cristina; Gratteri, Santo; Costanzo, Francesco S; Rotiroti, Domenicantonio

2006-01-01

Background 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. Results We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation. Conclusion Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties. PMID:16480519

Interactive Chemical Safety for Sustainablity Toxicity Forecaster Dashboard

EPA Pesticide Factsheets

EPA researchers have been using advances in computational toxicology to address lack of data on the thousands of chemicals. EPA released chemical data on 1,800 chemicals. The 1,800 chemicals were screened in more than 800 rapid, automated tests (called high-throughput screening assays) to determine potential human health effects. The data is available through the interactive Chemical Safety for Sustainability Dashboards (iCSS dashboard) and the complete data sets are also available for download.

The first toxicological study of the antiozonant and research tool ethylene diurea (EDU) using a Lemna minor L. bioassay: Hints to its mode of action.

PubMed

Agathokleous, Eugenios; Mouzaki-Paxinou, Akrivi-Chara; Saitanis, Costas J; Paoletti, Elena; Manning, William J

2016-06-01

The antiozonant and research tool ethylene diurea (EDU) is widely studied as a phytoprotectant against the widespread pollutant ground-surface ozone. Although it has been extensively used, its potential toxicity in the absence of ozone is unknown and its mode of action is unclear. The purpose of this research was to toxicologically assess EDU and to further investigate its mode of action using Lemna minor L. as a model organism. Application of EDU concentrations greater than 593 mg L(-1) (practically 600 mg L(-1)) resulted in adverse inhibition of colony growth. As no-observed-toxic-effects concentration (NOEL) we recommend a concentration of 296 mg L(-1) (practically 300 mg L(-1)). A hormetic response was detected, i.e. stimulatory effects of low EDU concentrations, which may indicate overcompensation in response to disruption in homeostasis. Growth inhibition and suppressed biomass were associated with impacted chlorophyll a fluorescence (ΦPSII, qP and ETR). Furthermore, EDU increased mesophyll thickness, as indicated by frond succulence index. Applications of concentrations ≥593 mg L(-1) to uncontrolled environments should be avoided due to potential toxicity to sensitive organisms and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse outcome pathways (AOPs): A framework to support predictive toxicology

EPA Science Inventory

High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

Validation of a Glucocorticoid Receptor Effects-Based Environmental Sample Screening Tool

EPA Science Inventory

Abstract describing study and results that will be presented in a seminar presentation to members of UNC-Chapel Hill Curriculum in Toxicology. This seminar presentation will be fulfilling the requirements of the USEPA-UNC Toxicology Cooperative Postdoctoral Training program.

GENDER-SPECIFIC DIFFERENCES IN THE RESPONSE OF MATURING GAMETES TO TOXIC INSULT

EPA Science Inventory

GENDER-SPECIFIC DIFFERENCES IN THE RESPONSE OF MATURING GAMETES TO TOXIC INSULT

Sally D. Perreault, U. S. Environmental Toxicology Division, National Health and Environmental Effects Research Laboratory, Reproductive Toxicology Division, Research Triangle Park, NC 27711

Titanium dioxide in our everyday life; is it safe?

PubMed Central

Skocaj, Matej; Filipic, Metka; Petkovic, Jana; Novak, Sasa

2011-01-01

Background Titanium dioxide (TiO2) is considered as an inert and safe material and has been used in many applications for decades. However, with the development of nanotechnologies TiO2 nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. Therefore increased human and environmental exposure can be expected, which has put TiO2 nanoparticles under toxicological scrutiny. Mechanistic toxicological studies show that TiO2 nanoparticles predominantly cause adverse effects via induction of oxidative stress resulting in cell damage, genotoxicity, inflammation, immune response etc. The extent and type of damage strongly depends on physical and chemical characteristics of TiO2 nanoparticles, which govern their bioavailability and reactivity. Based on the experimental evidence from animal inhalation studies TiO2 nanoparticles are classified as “possible carcinogenic to humans” by the International Agency for Research on Cancer and as occupational carcinogen by the National Institute for Occupational Safety and Health. The studies on dermal exposure to TiO2 nanoparticles, which is in humans substantial through the use of sunscreens, generally indicate negligible transdermal penetration; however data are needed on long-term exposure and potential adverse effects of photo-oxidation products. Although TiO2 is permitted as an additive (E171) in food and pharmaceutical products we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure. TiO2 may also enter environment, and while it exerts low acute toxicity to aquatic organisms, upon long-term exposure it induces a range of sub-lethal effects. Conclusions Until relevant toxicological and human exposure data that would enable reliable risk assessment are obtained, TiO2 nanoparticles should be used with great care. PMID:22933961

Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

PubMed

Wang, Ting; Guo, Rixin; Zhou, Guohong; Zhou, Xidan; Kou, Zhenzhen; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

2016-07-21

Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The State of the Art of the Zebrafish Model for Toxicology and Toxicologic Pathology Research—Advantages and Current Limitations

PubMed Central

Spitsbergen, Jan M.; Kent, Michael L.

2007-01-01

The zebrafish (Danio rerio) is now the pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. The zebrafish genome will be completely sequenced within the next 1–2 years. Together with the substantial historical database regarding basic developmental biology, toxicology, and gene transfer, the rich foundation of molecular genetic and genomic data makes zebrafish a powerful model system for clarifying mechanisms in toxicity. In contrast to the highly advanced knowledge base on molecular developmental genetics in zebrafish, our database regarding infectious and noninfectious diseases and pathologic lesions in zebrafish lags far behind the information available on most other domestic mammalian and avian species, particularly rodents. Currently, minimal data are available regarding spontaneous neoplasm rates or spontaneous aging lesions in any of the commonly used wild-type or mutant lines of zebrafish. Therefore, to fully utilize the potential of zebrafish as an animal model for understanding human development, disease, and toxicology we must greatly advance our knowledge on zebrafish diseases and pathology. PMID:12597434

Interpretation of postmortem forensic toxicology results for injury prevention research.

PubMed

Drummer, Olaf H; Kennedy, Briohny; Bugeja, Lyndal; Ibrahim, Joseph Elias; Ozanne-Smith, Joan

2013-08-01

Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings.

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.

Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays: role of known and unknown substances.

PubMed

Honkalampi-Hämäläinen, U; Bradley, E L; Castle, L; Severin, I; Dahbi, L; Dahlman, O; Lhuguenot, J-C; Andersson, M A; Hakulinen, P; Hoornstra, D; Mäki-Paakkanen, J; Salkinoja-Salonen, M; Turco, L; Stammati, A; Zucco, F; Weber, A; von Wright, A

2010-03-01

In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.

The nematode Caenorhabditis elegans as an integrated toxicological tool to assess water quality and pollution.

PubMed

Clavijo, Araceli; Kronberg, María Florencia; Rossen, Ariana; Moya, Aldana; Calvo, Daniel; Salatino, Santa Esmeralda; Pagano, Eduardo Antonio; Morábito, José Antonio; Munarriz, Eliana Rosa

2016-11-01

Determination of water quality status in rivers is critical to establish a sustainable water management policy. For this reason, over the last decades it has been recommended to perform integrated water assessments that include water quantities and physicochemical, ecological and toxicological tests. However, sometimes resources are limited and it is not possible to perform large-scale chemical determinations of pollutants or conduct numerous ecotoxicological tests. To overcome this problem we use and measure the growth, as a response parameter, of the soil nematode Caenorhabditis elegans to assess water quality in rivers. The C. elegans is a ubiquitous organism that has emerged as an important model organism in aquatic and soil toxicology research. The Tunuyán River Basin (Province of Mendoza, Argentina) has been selected as a representative traditional water monitoring system to test the applicability of the C. elegans toxicological bioassay to generate an integrated water quality evaluation. Jointly with the C. elegans toxic assays, physicochemical and bacteriological parameters were determined for each monitoring site. C. elegans bioassays help to identify different water qualities in the river basin. Multivariate statistical analysis (PCA and linear regression models) has allowed us to confirm that traditional water quality studies do not predict potential toxic effects on living organisms. On the contrary, physicochemical and bacteriological analyzes explain <62% of the C. elegans growth response variability, showing that ecotoxicological bioassays are important to obtain a realistic scenario of water quality threats. Our results confirm that the C. elegans bioassay is a sensible and suitable tool to assess toxicity and should be implemented in routine water quality monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Current and future needs for developmental toxicity testing.

PubMed

Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

2011-10-01

A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. © 2011 Wiley Periodicals, Inc.

"Seeing is believing": perspectives of applying imaging technology in discovery toxicology.

PubMed

Xu, Jinghai James; Dunn, Margaret Condon; Smith, Arthur Russell

2009-11-01

Efficiency and accuracy in addressing drug safety issues proactively are critical in minimizing late-stage drug attritions. Discovery toxicology has become a specialty subdivision of toxicology seeking to effectively provide early predictions and safety assessment in the drug discovery process. Among the many technologies utilized to select safer compounds for further development, in vitro imaging technology is one of the best characterized and validated to provide translatable biomarkers towards clinically-relevant outcomes of drug safety. By carefully applying imaging technologies in genetic, hepatic, and cardiac toxicology, and integrating them with the rest of the drug discovery processes, it was possible to demonstrate significant impact of imaging technology on drug research and development and substantial returns on investment.

Safety and Toxicology of Magnolol and Honokiol.

PubMed

Sarrica, Andrea; Kirika, Natalja; Romeo, Margherita; Salmona, Mario; Diomede, Luisa

2018-06-20

Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the Magnolia plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. In vitro and in vivo genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe. Georg Thieme Verlag KG Stuttgart · New York.

Assessment in rats of the reproductive toxicity of gasoline from a gasoline vapor recovery unit.

PubMed

McKee, R H; Trimmer, G W; Whitman, F T; Nessel, C S; Mackerer, C R; Hagemann, R; Priston, R A; Riley, A J; Cruzan, G; Simpson, B J; Urbanus, J H

2000-01-01

Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial products. Although numerous toxicology studies have been conducted, the potential for reproductive toxicity has not been directly assessed. Accordingly, a two-generation reproductive toxicity study in rats was conducted to provide base data for hazard assessment and risk characterization. The test material, vapor recovery unit gasoline (68514-15-8), is the volatile fraction of formulated gasoline and the material with which humans are most likely to come in contact. The study was of standard design. Exposures were by inhalation at target concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure concentration was approximately 50% of the lower explosive limit and several orders of magnitude above anticipated exposure during refueling. There were no treatment-related clinical or systemic effects in the parental animals, and no microscopic changes other than hyaline droplet nephropathy in the kidneys of the male rats. None of the reproductive parameters were affected, and there were no deleterious effects on offspring survival and growth. The potential for endocrine modulation was also assessed by analysis of sperm count and quality as well as time to onset of developmental landmarks. No toxicologically important differences were found. Therefore, the NOAEL for reproductive toxicity in this study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a male rat-specific effect and not relevant to human health risk assessment.

COMPUTER ANALYSIS OF PLANAR GAMMA CAMERA IMAGES

EPA Science Inventory

COMPUTER ANALYSIS OF PLANAR GAMMA CAMERA IMAGES

T Martonen1 and J Schroeter2

1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. EPA, Research Triangle Park, NC 27711 USA and 2Curriculum in Toxicology, Unive...

SYMPOSIUM IN ITALY: FISH PHYSIOLOGY, TOXICOLOGY, AND WATER QUALITY

EPA Science Inventory

Scientists from Europe, North America and South America convened in Capri, Italy, April 24-28, 2006 for the Ninth International Symposium on Fish Physiology, Toxicology, and Water Quality. The subject of the meeting was Eutrophication: The toxic effects of ammonia, nitrite and th...

Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

EPA Science Inventory

High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

DEVELOPMENTAL TOXICOLOGY EVALUATIONS -- ISSUES WITH INCLUDING NEUROTOXICOLOGY AND IMMUNOTOXICOLOGY ASSESSMENTS IN REPRODUCTIVE TOXICOLOGY STUDIES

EPA Science Inventory

Developmental and reproductive toxixology (DART) has routinely been a part of safety assessment. Attention is now focused on the effects of chemicals on the developing nervous and immune systems. This focus on developmental neurotoxicology (DNT) and developmental immunotoxicolo...

Moving from the laboratory to the field: Adding natural environmental conditions to toxicology testing

EPA Science Inventory

While laboratory toxicology tests are generally easy to perform, cost effective and readily interpreted, they have been criticized for being unrealistic. In contrast, field tests are considered realistic while producing results that are difficult to interpret and expensive. To ...

Toxicology and Chemical Safety.

ERIC Educational Resources Information Center

Hall, Stephen K.

1983-01-01

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

COMPUTATIONAL TOXICOLOGY ADVANCES: EMERGING CAPABILITIES FOR DATA EXPLORATION AND SAR MODEL DEVELOPMENT

EPA Science Inventory

Computational Toxicology Advances: Emerging capabilities for data exploration and SAR model development
Ann M. Richard and ClarLynda R. Williams, National Health & Environmental Effects Research Laboratory, US EPA, Research Triangle Park, NC, USA; email: richard.ann@epa.gov

Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

PubMed

Musshoff, F

2000-02-01

The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

Distance learning in toxicology: Resident and remote; Scotland, IPCS, IUPAC, and the world

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

Duffus, John H.

2005-09-01

Globally, very few college or university chemistry courses incorporate toxicology although public perception of chemicals and the chemical industry as threats to health and the environment has had an adverse effect on chemistry and on the use of its products. The International Union for Pure and Applied Chemistry (IUPAC) through its Commission on Toxicology recognized this and, with the support of the Committee on the Teaching of Chemistry has used the IUPAC web site to promote distance learning in toxicology for chemists. After preparation of a thoroughly refereed consensus Glossary of Terms for Chemists of Terms Used in Toxicology, amore » textbook Fundamental Toxicology for Chemists and a set of educational modules entitled Essential Toxicology were compiled and put through the normal thorough review procedure of IUPAC before being approved by the organization. There is now an additional Glossary of Terms Used in Toxicokinetics. The modules are freely downloadable in Adobe PDF format and are designed to be used both by educators and by students. Educators are asked to select whatever is appropriate to their students and to use the material as they wish, adding content specifically relevant to their circumstances. For self-study, the web modules have self-assessment questions and model answers. Currently the original Glossary for Chemists of Terms Used in Toxicology is being revised and it is expected that this will lead to further developments. The currently available components of the IUPAC programme may be accessed through the IUPAC website at the Subcommittee on Toxicology and Risk Assessment page: http://www.iupac.org/divisions/VII/VII.C.2/index.html.« less

Natural products-friends or foes?

PubMed

Margină, Denisa; Ilie, Mihaela; Grădinaru, Daniela; Androutsopoulos, Vasilis P; Kouretas, Demetrios; Tsatsakis, Aristidis M

2015-08-05

A trend in the general population has been observed in recent years regarding the orientation toward preventive measures in health; in this context the increased interest from the users and researchers concerning the active effect of food supplements on the health state and on longevity, is noticeable. All over the world, the consumption of natural foods and of vegetal supplements has increased spectacularly over the last 5-10 years. The decreased prevalence of cardio-vascular diseases associated with Mediterranean diet, as well as the French paradox convinced researchers to scientifically document the beneficial outcomes pointed out by traditional use of plants, and to try to develop supplements that would have the same positive effects as these noticed for diet components. The intense research dedicated to this topic revealed the fact that food supplements are linked to some problematic aspects, such as toxicological side effects when associated with classical synthetic drugs. The food supplement-drug interactions are submitted to complex issues regarding pharmacokinetic interactions leading to changes in absorption, distribution, metabolism and excretion processes with direct impact on effect and toxicological potential. The present review based on recent literature aims at discussing the food-drug interactions with direct impact on efficacy and toxicity of drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors.

PubMed

Hardman, Ron

2006-02-01

As a growing applied science, nanotechnology has considerable global socioeconomic value, and the benefits afforded by nanoscale materials and processes are expected to have significant impacts on almost all industries and all areas of society. A diverse array of engineered nanoscale products and processes have emerged [e.g., carbon nanotubes, fullerene derivatives, and quantum dots (QDs)], with widespread applications in fields such as medicine, plastics, energy, electronics, and aerospace. With the nanotechnology economy estimated to be valued at dollar 1 trillion by 2012, the prevalence of these materials in society will be increasing, as will the likelihood of exposures. Importantly, the vastness and novelty of the nanotechnology frontier leave many areas unexplored, or underexplored, such as the potential adverse human health effects resulting from exposure to novel nanomaterials. It is within this context that the need for understanding the potentially harmful side effects of these materials becomes clear. The reviewed literature suggests several key points: Not all QDs are alike; engineered QDs cannot be considered a uniform group of substances. QD absorption, distribution, metabolism, excretion, and toxicity depend on multiple factors derived from both inherent physicochemical properties and environmental conditions; QD size, charge, concentration, outer coating bioactivity (capping material and functional groups), and oxidative, photolytic, and mechanical stability have each been implicated as determining factors in QD toxicity. Although they offer potentially invaluable societal benefits such as drug targeting and in vivo biomedical imaging, QDs may also pose risks to human health and the environment under certain conditions. Key words: environment, human health, nanomaterials, nanosized particles, nanotechnology, nanotoxicology, quantum dots, toxicology.

The toxicology of inhaled woodsmoke.

PubMed

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

2002-01-01

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

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.

Functional Toxicogenomic Assessment of Triclosan in Human HepG2 Cells Using Genome-Wide CRISPR-Cas9 Screening.

PubMed

Xia, Pu; Zhang, Xiaowei; Xie, Yuwei; Guan, Miao; Villeneuve, Daniel L; Yu, Hongxia

2016-10-04

There are thousands of chemicals used by humans and detected in the environment for which limited or no toxicological data are available. Rapid and cost-effective approaches for assessing the toxicological properties of chemicals are needed. We used CRISPR-Cas9 functional genomic screening to identify the potential molecular mechanism of a widely used antimicrobial triclosan (TCS) in HepG2 cells. Resistant genes at IC50 (the concentration causing a 50% reduction in cell viability) were significantly enriched in the adherens junction pathway, MAPK signaling pathway, and PPAR signaling pathway, suggesting a potential role in the molecular mechanism of TCS-induced cytotoxicity. Evaluation of the top-ranked resistant genes, FTO (encoding an mRNA demethylase) and MAP2K3 (a MAP kinase kinase family gene), revealed that their loss conferred resistance to TCS. In contrast, sensitive genes at IC10 and IC20 were specifically enriched in pathways involved with immune responses, which was concordant with transcriptomic profiling of TCS at concentrations of

CUMULATIVE RISK ASSESSMENT: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS

EPA Science Inventory

INTRODUCTION: GETTING FROM TOXICOLOGY TO QUANTITATIVE ANALYSIS FOR CUMULATIVE RISK

Hugh A. Barton1 and Carey N. Pope2
1US EPA, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC
2Department of...

Using in vitro Dose-Response Profiles to Enhance QSAR Modeling of in vivo Toxicity

EPA Science Inventory

To develop effective means for rapid toxicity evaluation of environmental chemicals, the Tox21 partnership among the National Toxicology Program (NTP), NIH Chemical Genomics Center, and National Center for Computational Toxicology (NCCT) at the US EPA are conducting a number of ...

Occurrence of ²¹⁰Po and biological effects of low-level exposure: the need for research.

PubMed

Seiler, Ralph L; Wiemels, Joseph L

2012-09-01

Polonium-210 (²¹⁰Po) concentrations that exceed 1 Bq/L in drinking-water supplies have been reported from four widely separated U.S. states where exposure to it went unnoticed for decades. The radionuclide grandparents of ²¹⁰Po are common in sediments, and segments of the public may be chronically exposed to low levels of ²¹⁰Po in drinking water or in food products from animals raised in contaminated areas. We summarized information on the environmental behavior, biokinetics, and toxicology of ²¹⁰Po and identified the need for future research. Potential linkages between environmental exposure to ²¹⁰Po and human health effects were identified in a literature review. ²¹⁰Po accumulates in the ovaries where it kills primary oocytes at low doses. Because of its radiosensitivity and tendency to concentrate ²¹⁰Po, the ovary may be the critical organ in determining the lowest injurious dose for ²¹⁰Po. ²¹⁰Po also accumulates in the yolk sac of the embryo and in the fetal and placental tissues. Low-level exposure to ²¹⁰Po may have subtle, long-term biological effects because of its tropism towards reproductive and embryonic and fetal tissues where exposure to a single alpha particle may kill or damage critical cells. ²¹⁰Po is present in cigarettes and maternal smoking has several effects that appear consistent with the toxicology of ²¹⁰Po. Much of the important biological and toxicological research on ²¹⁰Po is more than four decades old. New research is needed to evaluate environmental exposure to ²¹⁰Po and the biological effects of low-dose exposure to it so that public health officials can develop appropriate mitigation measures where necessary.

E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks.

PubMed

Bourke, Liam; Bauld, Linda; Bullen, Christopher; Cumberbatch, Marcus; Giovannucci, Edward; Islami, Farhad; McRobbie, Hayden; Silverman, Debra T; Catto, James W F

2017-06-01

Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear. Copyright © 2017 European Association of Urology. All rights reserved.

Imaging mass spectrometry in drug development and toxicology.

PubMed

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

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

PubMed

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

2015-05-01

This study was conducted based on the evidence of fish habitats in North India being affected by organophosphate pesticides draining from agricultural fields into bodies of water, especially during the rainy season. Various tissues of fish such as scales, gills ovaries, kidney, and liver have been studied from the toxicological point of view, but the toxicological effects of aquatic pollutants on fish cornea have not been investigated to date. We conducted comparative toxicological studies on the cornea of Cyprinus carpio communis using two sublethal (0.038 and 0.126 ppm) concentrations of monocrotophos pesticide for 30 days. Corneas from all the groups were evaluated by a scanning electron microscope. The fish exposed to the monocrotophos pesticide developed corneal necrosis due to the formation of crystalloid-like structures, thinning and shrinkage of microridges on the corneal epithelium. After 30 days, fish from the monocrotophos-treated tank were transferred to normal environmental conditions. After 60 days under natural condition, epithelial cells did not fully recover. In conclusion, exposure to monocrotophos induces irreversible changes in the cornea of C. carpio communis. As fish and mammalian visual systems share many similarities, the reported finding may offer useful insights for further toxicological and ophthalmological studies in humans. © 2013 American College of Veterinary Ophthalmologists.

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

Intersection of toxicogenomics and high throughput screening in the Tox21 program: an NIEHS perspective.

PubMed

Merrick, B Alex; Paules, Richard S; Tice, Raymond R

Humans are exposed to thousands of chemicals with inadequate toxicological data. Advances in computational toxicology, robotic high throughput screening (HTS), and genome-wide expression have been integrated into the Tox21 program to better predict the toxicological effects of chemicals. Tox21 is a collaboration among US government agencies initiated in 2008 that aims to shift chemical hazard assessment from traditional animal toxicology to target-specific, mechanism-based, biological observations using in vitro assays and lower organism models. HTS uses biocomputational methods for probing thousands of chemicals in in vitro assays for gene-pathway response patterns predictive of adverse human health outcomes. In 1999, NIEHS began exploring the application of toxicogenomics to toxicology and recent advances in NextGen sequencing should greatly enhance the biological content obtained from HTS platforms. We foresee an intersection of new technologies in toxicogenomics and HTS as an innovative development in Tox21. Tox21 goals, priorities, progress, and challenges will be reviewed.

Forensic toxicology in drug-facilitated sexual assault.

PubMed

Dinis-Oliveira, Ricardo Jorge; Magalhães, Teresa

2013-09-01

The low rates of reporting, prosecution and conviction that characterize sexual assault, is likely even more evident in drug-facilitated cases. Typically, in these crimes, victims are incapacitated and left unable to resist sexual advances, unconscious, unable to fight off the abuser or to say "no" and unable to clearly remember the circumstances surrounding the events due to anterograde amnesia. The consequence is the delay in performing toxicological analysis aggravated by the reluctance of the victim to disclose the crime. Moreover since "date rape drugs" are often consumed with ethanol and exhibit similar toxicodynamic effects, the diagnosis is erroneously performed as being classical ethanol intoxication. Therefore, it is imperative to rapidly consider toxicological analysis in drug-facilitated sexual assaults. The major focus of this review is to harmonize practical approaches and guidelines to rapidly uncover drug-facilitated sexual assault, namely issues related to when to perform toxicological analysis, toxicological requests, samples to be collected, storage, preservation and transport precautions and xenobiotics or endobiotics to be analyzed.

NIEHS/FDA CLARITY-BPA research program update.

PubMed

Heindel, Jerrold J; Newbold, Retha R; Bucher, John R; Camacho, Luísa; Delclos, K Barry; Lewis, Sherry M; Vanlandingham, Michelle; Churchwell, Mona I; Twaddle, Nathan C; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A; Flaws, Jodi; Howard, Paul C; Walker, Nigel J; Zoeller, R Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T

2015-12-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. Published by Elsevier Inc.

NIEHS/FDA CLARITY-BPA research program update

PubMed Central

Heindel, Jerrold J.; Newbold, Retha R.; Bucher, John R.; Camacho, Luísa; Delclos, K. Barry; Lewis, Sherry M.; Vanlandingham, Michelle; Churchwell, Mona I.; Twaddle, Nathan C.; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; Gamboa da Costa, Gonçalo; Ferguson, Sherry A.; Flaws, Jodi; Howard, Paul C.; Walker, Nigel J.; Zoeller, R. Thomas; Fostel, Jennifer; Favaro, Carolyn; Schug, Thaddeus T.

2016-01-01

Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. PMID:26232693

A Toxicological Evaluation of a Standardized Hydrogenated Extract of Curcumin (CuroWhite™)

PubMed Central

Ravikumar, Alastimmanahalli Narasimhiah; Jacob, Joby

2018-01-01

A series of toxicological investigations were conducted in order to evaluate the genotoxic potential and repeated-dose oral toxicity of CuroWhite, a proprietary extract of curcumin that has been hydrogenated and standardized to not less than 25% hydrogenated curcuminoid content. All tests were conducted in general accordance with internationally accepted standards. The test item was not mutagenic in the bacterial reverse mutation test or in vitro mammalian chromosomal aberration test, and no in vivo genotoxic activity was observed in rat bone marrow in the micronucleus test. A 90-day repeated-dose study was conducted in male and female Sprague-Dawley rats. Two mortalities occurred in the main and satellite high-dose groups and were determined due to gavage error. No organ specific or other toxic effects of the test item were observed up to the maximum dose of 800 mg/kg bw/day, administered by gavage. NOAEL was, therefore, estimated as 800 mg/kg bw/day. PMID:29610573

Zebrafish embryo developmental toxicology assay.

PubMed

Panzica-Kelly, Julieta M; Zhang, Cindy X; Augustine-Rauch, Karen

2012-01-01

A promising in vitro zebrafish developmental toxicology assay was generated to test compounds for their teratogenic potential. The assay's predictivity is approximately 87% in AB strain fish (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010). The procedure entails exposing dechorionated gastrulation-stage embryos to a range of compound concentrations for 5 days throughout embryonic and larva development. The larvae are evaluated for viability in order to identify an LC25 (the compound concentration in which 25% lethality is observed) and morphological anomalies using a numerical score system to identify the NOAEL (no observed adverse effect level). These values are used to calculate the teratogenic index (LC25/NOAEL ratio) of each compound. If the teratogenic index is equal to or greater than 10 then the compound is classified as a teratogen, and if the ratio is less than 10 then the compound is classified as a nonteratogen (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010).

A Toxicological Evaluation of a Standardized Hydrogenated Extract of Curcumin (CuroWhite™).

PubMed

Ravikumar, Alastimmanahalli Narasimhiah; Jacob, Joby; Gopi, Sreeraj; Jagannath, Tumkur Subbarao

2018-01-01

A series of toxicological investigations were conducted in order to evaluate the genotoxic potential and repeated-dose oral toxicity of CuroWhite, a proprietary extract of curcumin that has been hydrogenated and standardized to not less than 25% hydrogenated curcuminoid content. All tests were conducted in general accordance with internationally accepted standards. The test item was not mutagenic in the bacterial reverse mutation test or in vitro mammalian chromosomal aberration test, and no in vivo genotoxic activity was observed in rat bone marrow in the micronucleus test. A 90-day repeated-dose study was conducted in male and female Sprague-Dawley rats. Two mortalities occurred in the main and satellite high-dose groups and were determined due to gavage error. No organ specific or other toxic effects of the test item were observed up to the maximum dose of 800 mg/kg bw/day, administered by gavage. NOAEL was, therefore, estimated as 800 mg/kg bw/day.

Dextromethorphan abuse leading to assault, suicide, or homicide.

PubMed

Logan, Barry K; Yeakel, Jillian K; Goldfogel, Gary; Frost, Michael P; Sandstrom, Greg; Wickham, Dennis J

2012-09-01

Dextromethorphan is a commonly encountered antitussive medication which has found additional therapeutic use in the treatment of pseudobulbar disorder and as an adjunct to opiate use in pain management. Dextromethorphan at high doses has phencyclidine-like effects on the NMDA receptor system; recreational use of high doses has been found to cause mania and hallucinations. The toxicology and pharmacology of the drug in abuse are reviewed, and the historical literature of adverse psychiatric outcomes is assessed. Five new cases of dextromethorphan intoxication that resulted in assault, suicide, and homicide are reported, together with the corresponding toxicology results. Blood concentrations ranged from 300 to 19,000 μg/L. These results are compared with typical concentrations reported in therapeutic use and impaired driving cases. Based on these findings, dextromethorphan should be considered as a potential causative agent in subjects presenting with mania, psychosis, or hallucinations, and abusers are at risk for violent and self-destructive acts. © 2012 American Academy of Forensic Sciences.

A new medium for Caenorhabditis elegans toxicology and nanotoxicology studies designed to better reflect natural soil solution conditions.

PubMed

Tyne, William; Lofts, Stephen; Spurgeon, David J; Jurkschat, Kerstin; Svendsen, Claus

2013-08-01

A new toxicity test medium for Caenorhabditis elegans is presented. The test solution is designed to provide a better representation of natural soil pore water conditions than currently available test media. The medium has a composition that can readily be modified to allow for studies of the influences of a range of environmentally relevant parameters on nematode biology and toxicology. Tests conducted in the new medium confirmed that nematodes' reproduction was possible at a range of solution pH levels, offering the potential to conduct toxicity studies under a variety of conditions. A test to establish silver nanoparticle and dissolved silver nitrate toxicity, a study type not feasible in M9 or agar media due to precipitation and nanoparticle agglomeration, indicated lower silver nanoparticle (median effective concentration [EC50] of 6.5 mg Ag/L) than silver nitrate (EC50 0.28 mg Ag/L) toxicity. Characterization identified stable nanoparticle behavior in the new test medium. Copyright © 2013 SETAC.

Applicability of computational systems biology in toxicology.

PubMed

Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

2014-07-01

Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food.

PubMed

Bakhiya, Nadiya; Abraham, Klaus; Gürtler, Rainer; Appel, Klaus Erich; Lampen, Alfonso

2011-04-01

Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 μg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[The present study situation and application prospect of nail analysis for abused drugs].

PubMed

Chen, Hang; Xiang, Ping; Shen, Min

2010-10-01

In forensic toxicology analysis, various types of biological samples have their own special characteristics and scope of applications. In this article, the physiological structure of nails, methods for collecting and pre-processing samples, and for analyzing some poisons and drugs in the nails are reviewed with details. This paper introduces the influence factors of drug abuse of the nails. The prospects of its further applications are concluded based on the research results. Nails, as an unconventional bio-sample without general application, show great potential and advantages in forensic toxicology.

Toxicology Study No. S.0024589d 15, Human Cell Line Activation Test of the Novel Energetic, 3,4 -Dinitropyrazole (DNP)

DTIC Science & Technology

2016-04-01

potential. The h-CLAT is one of many non- animal skin sensitizing tests , and it comprises part of an integrated testing strategy with two other in vitro...Protocol No. 158. 2015: European Union Reference Laboratory for Alternatives to Animal Testing [18, 19]. Toxicology Study No. S.0024589d-15, April...Alternatives to Animal Testing [18, 19]. If the EC200 or EC150 fell below the lowest dose, the values were extrapolated by the following equations

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.

PubMed

Aigner, Achim; Buesen, Roland; Gant, Tim; Gooderham, Nigel; Greim, Helmut; Hackermüller, Jörg; Hubesch, Bruno; Laffont, Madeleine; Marczylo, Emma; Meister, Gunter; Petrick, Jay S; Rasoulpour, Reza J; Sauer, Ursula G; Schmidt, Kerstin; Seitz, Hervé; Slack, Frank; Sukata, Tokuo; van der Vies, Saskia M; Verhaert, Jan; Witwer, Kenneth W; Poole, Alan

2016-12-01

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

In silico toxicology protocols.

PubMed

Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

2018-07-01

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The local lymph node assay in 2014.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2014-01-01

Toxicology endeavors to predict the potential of materials to cause adverse health (and environmental) effects and to assess the risk(s) associated with exposure. For skin sensitizers, the local lymph node assay was the first method to be fully and independently validated, as well as the first to offer an objective end point with a quantitative measure of sensitizing potency (in addition to hazard identification). Fifteen years later, it serves as the primary standard for the development of in vitro/in chemico/in silico alternatives.

Development of Intake Retention, and Excretion Fractions used in Bioassay Programs for Metallic Nanoparticle Aerosols Produced in Modern Munitions Development

DTIC Science & Technology

2014-03-01

potential toxicological effects of tungsten-compounds are often attributed to the presence of cobalt and or chromium which are frequently contained in...rat test subjects.4 These claims were later put in doubt because of the substantial presents of chromium and cobalt in the tungsten alloy. Very little...biokinetics of aluminum follow similar trends as other trivalent metals. Of specific importance to this work, Priest made the assertion that

A toxicological study of 1,2,4-triazole-5-one

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

London, J.

1988-12-01

The acute oral LD/sub 50/ values for 1,2,4-triazole-5-one (TO) are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show TO to have potential sensitizing effects. Skin application studies on the rabbit demonstrated it was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies. 4 refs., 1 tab.

Reviews of environmental contamination and toxicology

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

Ware, G.

2007-07-01

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

REPORT ON THE PEER REVIEW OF THE U.S. EPA'S "Perchlorate ENVIRONMENTAL CONTAMINATION: TOXICOLOGICAL REVIEW AND RISK CHARACTERIZATION (External Review Draft)" 2002

EPA Science Inventory

This report summarizes the comments made at a two-day independent scientific peer review meeting on the Agency's draft assessment of health and ecotoxicological effects of perchlorate, entitled Perchlorate Environmental Contamination: Toxicological Review and Risk Characteriza...