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Critical Reviews in Toxicology

Peter T Theunissen, Sonia Beken, Bruce Beyer, William J Breslin, Gregg D Cappon, Connie L Chen, Gary Chmielewski, Luc de Schaepdrijver, Brian Enright, Jennifer E Foreman, Wafa Harrouk, Kok-Wah Hew, Alan M Hoberman, Julia Y Hui, Thomas B Knudsen, Susan B Laffan, Susan L Makris, Matthew Martin, Mary Ellen McNerney, Christine L Siezen, Dinesh J Stanislaus, Jane Stewart, Kary E Thompson, Belen Tornesi, Jan Willem Van der Laan, Gerhard F Weinbauer, Sandra Wood, Aldert H Piersma
A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures...
October 21, 2016: Critical Reviews in Toxicology
Anne Harman Chappelle, Mark Spence, Bernard Tury
No abstract text is available yet for this article.
October 18, 2016: Critical Reviews in Toxicology
Mohamed B Abou-Donia, Briana Siracuse, Natasha Gupta, Ashly Sobel Sokol
Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as "cholinergic crisis" (i...
October 5, 2016: Critical Reviews in Toxicology
Lynn E Secondo, Nathan J Liu, Nastassja A Lewinski
Little consistency exists in the methodology for toxicological testing of aerosolized nanoparticles used in in vitro, air-interfaced culture (AIC) exposure systems for engineered nanoparticles (ENPs) risk-assessment, preventing inter-laboratory comparisons to identify dose thresholds for adverse effects. These inconsistencies result from heterogeneity in particle types, exposure durations, exposure systems, and dose metrics reported. We screened 10,241 studies in the literature for toxicological assessment of ENPs, resulting in 110 publications included after meeting eligibility criteria...
September 20, 2016: Critical Reviews in Toxicology
Xu Wang, María Aránzazu Martínez, Qinghua Wu, Irma Ares, María Rosa Martínez-Larrañaga, Arturo Anadón, Zonghui Yuan
Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates...
September 19, 2016: Critical Reviews in Toxicology
(no author information available yet)
No abstract text is available yet for this article.
September 12, 2016: Critical Reviews in Toxicology
Peter J Boogaard, Juan-Carlos Carrillo, Linda G Roberts, Graham F Whale
Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons, primarily linear alkanes, with increasing amounts of branched (methyl-groups) alkanes as the chains get longer. In addition, small amounts of cycloalkanes (branched cyclopentanes and cyclohexanes) may be formed as the polymerization reaction prolongs. This synthetic crude can subsequently be refined to a range of products very similar to petroleum refining...
August 25, 2016: Critical Reviews in Toxicology
Eileen D Kuempel, Marie-Claude Jaurand, Peter Møller, Yasuo Morimoto, Norihiro Kobayashi, Kent E Pinkerton, Linda M Sargent, Roel C H Vermeulen, Bice Fubini, Agnes B Kane
In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs)...
August 18, 2016: Critical Reviews in Toxicology
Angelo Moretto, Ammie Bachman, Alan Boobis, Keith R Solomon, Timothy P Pastoor, Martin F Wilks, Michelle R Embry
The ILSI Health and Environmental Sciences Institute (HESI) has developed a framework to support a transition in the way in which information for chemical risk assessment is obtained and used (RISK21). The approach is based on detailed problem formulation, where exposure drives the data acquisition process in order to enable informed decision-making on human health safety as soon as sufficient evidence is available. Information is evaluated in a transparent and consistent way with the aim of optimizing available resources...
August 11, 2016: Critical Reviews in Toxicology
Warren G Foster, Jane A Evans, Julian Little, Laura Arbour, Aideen Moore, Reg Sauve, Juan Andrés León, Wei Luo
Congenital anomalies are an important cause of infant mortality and disability. Developmental exposure to environmental contaminants is thought to increase the risk for congenital anomalies. Herein, we describe a critical review of the literature conducted between February and March 2014 yielding 3057 references from which 97 unique relevant articles published from 2003 through 2014 were evaluated. Common congenital anomalies including hypospadias, cryptorchidism, anogenital distance (AGD), congenital heart defects and oral clefts were well represented in the literature whereas other outcomes such as neural tube defects, limb deficiency defects and gastroschisis were rarely described...
August 11, 2016: Critical Reviews in Toxicology
Richard J Albertini, Debra A Kaden
Formaldehyde (FA) is a mutagenic chemical - a property mitigated in vivo by rapid detoxification and limited tissue distribution following inhalation of the free agent. Endogenously produced FA is necessary for life and required for one-carbon transfer reactions; however, FA derived from external sources (exogenous FA), which may be in the form of methanol, may increase in vivo concentrations above naturally occurring physiological levels. Both endogenous and exogenous FA produce DNA monoadducts, DNA-DNA and DNA-protein cross-links (DDX and DPX) but, when exposed to exogenously-derived free FA, DNA monoadducts, DDX, and DPX are only produced at initial sites of contact...
August 11, 2016: Critical Reviews in Toxicology
Keith R Solomon, Martin F Wilks, Ammie Bachman, Alan Boobis, Angelo Moretto, Timothy P Pastoor, Richard Phillips, Michelle R Embry
When the human health risk assessment/risk management paradigm was developed, it did not explicitly include a "problem formulation" phase. The concept of problem formulation was first introduced in the context of ecological risk assessment (ERA) for the pragmatic reason to constrain and focus ERAs on the key questions. However, this need also exists for human health risk assessment, particularly for cumulative risk assessment (CRA), because of its complexity. CRA encompasses the combined threats to health from exposure via all relevant routes to multiple stressors, including biological, chemical, physical and psychosocial stressors...
August 11, 2016: Critical Reviews in Toxicology
Katie Paul Friedman, Sabitha Papineni, M Sue Marty, Kun Don Yi, Amber K Goetz, Reza J Rasoulpour, Pat Kwiatkowski, Douglas C Wolf, Ann M Blacker, Richard C Peffer
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...
October 2016: Critical Reviews in Toxicology
Jason R Rohr, Christopher J Salice, Roger M Nisbet
Ecological risk assessment (ERA) is the process used to evaluate the safety of manufactured chemicals to the environment. Here we review the pros and cons of ERA across levels of biological organization, including suborganismal (e.g., biomarkers), individual, population, community, ecosystem and landscapes levels. Our review revealed that level of biological organization is often related negatively with ease at assessing cause-effect relationships, ease of high-throughput screening of large numbers of chemicals (it is especially easier for suborganismal endpoints), and uncertainty of the ERA because low levels of biological organization tend to have a large distance between their measurement (what is quantified) and assessment endpoints (what is to be protected)...
October 2016: Critical Reviews in Toxicology
Cathrine Carlsen Bach, Anne Vested, Kristian Tore Jørgensen, Jens Peter Ellekilde Bonde, Tine Brink Henriksen, Gunnar Toft
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers...
October 2016: Critical Reviews in Toxicology
David Brusick, Marilyn Aardema, Larry Kier, David Kirkland, Gary Williams
In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA...
September 2016: Critical Reviews in Toxicology
Gary M Williams, Colin Berry, Michele Burns, Joao Lauro Viana de Camargo, Helmut Greim
Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study...
September 2016: Critical Reviews in Toxicology
John Acquavella, David Garabrant, Gary Marsh, Tom Sorahan, Douglas L Weed
We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) - two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses...
September 2016: Critical Reviews in Toxicology
Keith R Solomon
The recent classification of glyphosate as a probable human carcinogen by the International Agency for Research on Cancer (IARC) was arrived at without a detailed assessment of exposure. Glyphosate is widely used as an herbicide, which might result in exposures of the general public and applicators. Exposures were estimated from information in the open literature and unpublished reports provided by Monsanto Company. Based on the maximum measured concentration in air, an exposure dose of 1.04 × 10 (-) (6 )mg/kg body mass (b...
September 2016: Critical Reviews in Toxicology
Gary M Williams, Marilyn Aardema, John Acquavella, Sir Colin Berry, David Brusick, Michele M Burns, Joao Lauro Viana de Camargo, David Garabrant, Helmut A Greim, Larry D Kier, David J Kirkland, Gary Marsh, Keith R Solomon, Tom Sorahan, Ashley Roberts, Douglas L Weed
The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies...
September 2016: Critical Reviews in Toxicology
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