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Although animal models cannot exactly replicate human psychiatric disorders, they may be useful to investigate whether the behaviors associated with certain exposures in animals parallel those observed in people. According to the most current version of the Diagnostic and Statistical Manual of Mental Disorders, autism is diagnosed based on (1) persistent deficits in social communication and social interaction; and (2) the presence of restricted, repetitive patterns of behavior, interests and activities. To address whether developmental chlorpyrifos (CPF) exposure was associated with the development of autistic behaviors, a literature search was conducted to identify studies in rats and mice involving gestational or early postnatal exposure to CPF or CPF oxon (CPO, the active metabolite of CPF) and subsequent behavioral testing to assess behaviors related to autism. A total of 13 studies conducted in six different laboratories were identified. Analysis of these studies found that perinatal CPF exposure was generally associated with (1) no effect or increased social communications; (2) no effect or increased social encounters; (3) no effect, reduced stereotypies, or conflicting findings on stereotypic behaviors; and (4) no effect or increased preference for novelty and reduced anxiety in novel environments. These behavioral findings are generally inconsistent with the types of behaviors that would be expected in children with clinical autism. Based on the results of this analysis of rodent model studies involving CPF/CPO exposure, it cannot be concluded that gestational and/or perinatal CPF exposure is likely to be associated with the development of autism-like behaviors in humans. [ABSTRACT FROM AUTHOR]

Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations. [ABSTRACT FROM AUTHOR]

Various brominated flame retardants (BFR), including polybrominated diphenyl ether (PBDE) congeners, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), are commonly used in household items and electronics and have been detected in the environment and/or the bodily fluids of people, including children. Some studies in animals suggest that exposure to PBDE congeners, HBCD, or TBBPA during the perinatal period may affect locomotor activity and/or memory and learning. Epidemiological studies showing similar effects in humans, however, are lacking. To assess whether an association exists between perinatal exposure and development of consistent neurobehavioral alterations, published animal studies investigating perinatal exposure to PBDE congeners, HBCD, or TBBPA with specific neurobehavioral evaluations—particularly, assessments of motor activity—were reviewed for consistency of results. Our analysis shows that although the majority of studies suggest that perinatal exposure affects motor activity, the effects observed were not consistent. This lack of consistency includes the type of motor activity (locomotion, rearing, or total activity) affected, the direction (increase or decrease) and pattern of change associated with exposure, the existence of a dose response, the permanency of findings, and the possibility of gender differences in response. Interestingly, Good Laboratory Practices (GLP)-compliant studies that followed U.S. Environmental Protection Agency (EPA)/Organization for Economic Cooperation and Development (OECD) guidelines for developmental neurotoxicity testing found no adverse effects associated with exposure to PBDE209, HBCD, or TBBPA at doses that were orders of magnitude higher and administered over longer durations than those used in the other studies examined herein. The lack of consistency across studies precludes establishment of a causal relationship between perinatal exposure to these substances and alterations in motor activity. [ABSTRACT FROM AUTHOR]

An evaluation of the scientific literature for trichloroethylene (TCE) identified two reports of ocular defects, specifically microphthalmia/anophthalmia, following prenatal TCE exposure in rats. Herein, these reports are analyzed in detail and interpreted within the context of other developmental TCE exposure studies. The ocular findings following prenatal TCE exposure are reported in studies that were not designed specifically for developmental safety assessment, and thus did not use standard experimental practices. Furthermore, these findings most commonly occurred at TCE doses associated with considerable maternal toxicity. Among the 18 published studies using developmental TCE exposures, only 3 used doses sufficiently high enough to result in maternal toxicity, and of these, only the 2 discussed in detail in this paper demonstrated ocular defects in the offspring. Furthermore, statistically significant effects were only observed at doses that were above the currently accepted guideline limit dose of 1000 mg/kg body weight. All other TCE developmental exposure studies failed to demonstrate ocular defects as a result of prenatal exposure. These results suggest that the micro-/anophthalmia findings were likely a consequence of delivery of an extremely high bolus TCE dose that is irrelevant to human environmental exposure scenarios. [ABSTRACT FROM AUTHOR]

Background: Air ions are molecules of air that have become ionized-that is, they have either lost or gained an electrical charge. Past speculation has suggested that exposure to positive air ions may be harmful to one's health, while exposure to negative air ions may be associated with beneficial health effects. Air ions arise from natural sources as well as direct-current transmission lines and commercial ionizers. Several recent clinical studies have suggested therapeutic effects of air ions on various types of depression at exposure levels 10- to 1000-fold higher than most previous human studies. The aim of this study was to assess the evidence from studies of laboratory animals for beneficial or adverse effects of air ions on health.Methods: Sixty-two studies (1935-2015) in nine topics areas were evaluated for quality and potential systematic bias by ARRIVE guidelines. Standardized mean differences or proportional differences between exposed and control groups were computed for 44 studies to quantitatively assess the strength of the evidence for exposure-related effects.Results: Many of the studies were conducted before 1990 and exhibited various reporting and methodological deficiencies, including small sample size, failure to control for the influence of potential confounding variables, lack of randomized assignment to treatment groups and blinded analyses, and statistical errors relating to treating group-exposed animals as individuals. The highest quality studies consistently reported no effects of exposure on any of the endpoints examined. There were no evident dose-response relationships within or across studies.Conclusions: Experimental studies of laboratory animals exposed to positive and negative air ions for minutes to years over a five-log unit range of intensities did not suggest any consistent or reliable effects on measures of behavior, learning and memory, neurotransmitters, tracheal function, respiratory infection, cardiovascular function, reproduction and growth, carcinogenesis, or other health endpoints. These data do not provide evidence of adverse or beneficial effects of air ion exposure on health, and did not suggest any biological mechanism of interaction, except perhaps for mechanosensory stimulation of body surfaces by static electric fields at high air ion concentrations. [ABSTRACT FROM AUTHOR]

To determine the reliability of food safety studies carried out in rodents with genetically modified (GM) crops, a Food Safety Study Reliability Tool (FSSRTool) was adapted from the European Centre for the Validation of Alternative Methods' (ECVAM) ToxRTool. Reliability was defined as the inherent quality of the study with regard to use of standardized testing methodology, full documentation of experimental procedures and results, and the plausibility of the findings. Codex guidelines for GM crop safety evaluations indicate toxicology studies are not needed when comparability of the GM crop to its conventional counterpart has been demonstrated. This guidance notwithstanding, animal feeding studies have routinely been conducted with GM crops, but their conclusions on safety are not always consistent. To accurately evaluate potential risks from GM crops, risk assessors need clearly interpretable results from reliable studies. The development of the FSSRTool, which provides the user with a means of assessing the reliability of a toxicology study to inform risk assessment, is discussed. Its application to the body of literature on GM crop food safety studies demonstrates that reliable studies report no toxicologically relevant differences between rodents fed GM crops or their non-GM comparators. [ABSTRACT FROM AUTHOR]

Abstract: The organic solvent trichloroethylene (TCE) is a metal degreasing agent and an intermediate in the production of fluorochemicals and polyvinyl chloride. TCE is also a common, persistent drinking water contaminant. Several epidemiological studies have alleged links between TCE exposure during pregnancy and offspring health problems including congenital heart defects (CHDs); however, the results of these studies are inconsistent, difficult to interpret, and involve several confounding factors. Similarly, the results of animal studies examining the potential of TCE to elicit cardiac anomalies have been inconsistent, and they have often been performed at doses far exceeding the highest levels ever reported in the drinking water. To determine what is known about the relationship between TCE and the incidence of CHDs, a comprehensive analysis of all available epidemiological data and animal studies was performed. Additionally, in vivo and in vitro studies examining possible mechanisms of action for TCE were evaluated. The specific types of heart defects alleged to have been caused by TCE in animal and human epidemiology studies were categorized by the morphogenetic process responsible for the defect in order to determine whether TCE might disrupt any specific developmental process. This analysis revealed that no single process was clearly affected by TCE, providing support that gestational TCE exposure does not increase the prevalence of CHDs. As a final evaluation, application of Hill''s causality guidelines to the collective body of data revealed no indication of a causal link between gestational TCE exposure at environmentally relevant concentrations and CHDs. [Copyright &y& Elsevier]

Regulatory interest in assessing the health effects of vanadium compounds is hindered by the limited chronic toxicity data available. The National Toxicology Program (NTP) conducted a robust chronic inhalation bioassay of crystalline vanadium pentoxide (V 2 O 5), but this study has noteworthy limitations. Multiple dose range-finding studies were conducted at two separate laboratories that showed cross-laboratory differences in lung pathology (inflammation) in both species and likely complicated dose-selection. In mice, the only tissue pathology (inflammation and tumors) was at the site of entry, the respiratory system. Although significantly different from control, because lung tumor incidences were at a maximal level across all concentrations tested, the ability to extrapolate risks to the public is problematic. In rats, lung inflammation and vanadium lung burdens were comparable to those of mice, but lung tumorigenicity was not substantiated, further raising questions about appropriate species extrapolation. Open questions also exist regarding test material chemical characterization, as the laboratory relied on vanadium measurement in test chambers as a surrogate for V 2 O 5. In sum, the NTP V 2 O 5 study does not provide an appropriate dataset for purposes of classification and risk assessment. Additional repeat exposure studies of vanadium compounds are needed and recommendations for future studies are provided. • The NTP V 2 O 5 chronic inhalation studies have methodological limitations to their utility for health assessments. • These studies measured chamber V concentrations, notV 2 O 5 , which is reactive and for which stability cannot be assumed. • Cross-lab and species differences in lung pathology/tumors were apparent, limiting extrapolation to humans. • Exposure concentrations were excessive; lung irritation/inflammation were apparent with short duration exposures. • Recommendations are included for future research to understand MOA and the relevance for human health. [ABSTRACT FROM AUTHOR]

Abstract: Industry and government institutions need a credible approach for evaluating and responding to emerging public health issues. Representatives of industry, government, and academia met under the auspices of the International Life Sciences Institute’s Health and Environmental Sciences Institute (HESI) to develop successful strategies for dealing with emerging issues based on historical case studies. The case studies chosen for evaluation were (1) tampon use and toxic shock syndrome; (2) hazardous waste and childhood cancer risk in Toms River, New Jersey; (3) fenfluramine and phentermine use and valvular heart disease; (4) silicone breast implants and cancer and auto-immune disease; and (5) progestational drugs and birth defects. We identified eight lessons from these case studies. Foremost, we recommend that public and private institutions not defer action until an issue is scientifically resolved and stress that cooperation among issue stakeholders is critical for effective issue resolution. We suggest establishing a research program as an effective way to assure that good science is included in resolution of the issue. We further recommend frequent and timely communication with all stakeholders, and the development of research approaches to fill gaps when the scientific data on an issue are limited. [Copyright &y& Elsevier]