Effects of Neonicotinoid Pesticide Exposure on Human Health: A Systematic Review.

BACKGROUND: Numerous studies have identified detectable levels of neonicotinoids (neonics) in the environment, adverse effects of neonics in many species including mammals, and pathways through which human exposure to neonics could occur, yet little is known about the human health effects of neonic exposure. OBJECTIVE: This systematic review sought to identify human population studies on the health effects of neonics. METHODS: Studies published in English between 2005 and 2015 were searched using PubMed, Scopus, and Web of Science databases. No restrictions were placed on the type of health outcome assessed. Risk of bias was assessed using guidance developed by the National Toxicology Program\u27s Office of Health Assessment and Translation. RESULTS: Eight studies investigating the human health effects of exposure to neonics were identified. Four examined acute exposure: three neonic poisoning studies reported two fatalities (n=1280 cases) and an occupational exposure study of 19 forestry workers reported no adverse effects. Four general population studies reported associations between chronic neonic exposure and adverse developmental or neurological outcomes, including tetralogy of Fallot (AOR 2.4, 95% CI: 1.1-5.4), anencephaly (AOR 2.9, 95% CI: 1.0-8.2), autism spectrum disorder (AOR 1.3, 95% CrI: 0.78-2.2), and a symptom cluster including memory loss and finger tremor (OR 14, 95% CI: 3.5-57). Reported odds ratios were based on exposed compared to unexposed groups. CONCLUSIONS: The studies conducted to date were limited in number with suggestive but methodologically weak findings related to chronic exposure. Given the wide-scale use of neonics, more needs to be known about their human health effects

Large Effects from Small Exposures. I. Mechanisms for Endocrine-Disrupting Chemicals with Estrogenic Activity

Reproduced with permission from Environmental Health Perspectives. doi:10.1289/ehp.5494Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses.Support during the preparation of this manuscript was provided by the W. Alton Jones Foundation to K.A.T, as well as by grants from the National Institutes of Health (NIH) (CA50354) and the University of Missouri (VMFC0018) to W.V.W and NIH (ES08293 and ES11283), U.S. Environmental Protection Agency (U914991), and University of Missouri Research Board to F.v.S

Workgroup Report: National Toxicology Program Workshop on Hormonally Induced Reproductive Tumors—Relevance of Rodent Bioassays

The National Toxicology Program (NTP) is currently reviewing its research portfolio as part of its efforts to implement the NTP Roadmap to achieve the NTP Vision for the 21st century. This review includes a recent workshop, “Hormonally Induced Reproductive Tumors—Relevance of Rodent Bioassays,” held 22–24 May 2006, that was organized to determine the adequacy and relevance to human disease outcome of rodent models currently used in the 2-year bioassay for four types of hormonally induced reproductive tumors (ovary, mammary gland, prostate, and testis). In brief, none of the workshop’s breakout groups felt the currently used models are sufficient. For some types of tumors such as prostate, no adequate animal models exist, and for others such as ovary, the predominant tumors in humans are of different cellular origins than those induced by chemicals in rodents. This inadequacy of current models also applies to the testis, although our more complete understanding of the responses of Leydig cells to hormonal changes in rats may prove predictive for effects in humans other than cancer. All breakout groups recommended that the NTP consider modifying its testing protocols (i.e., age at exposure, additional end points, etc.) and/or using alternative models (i.e., genetically engineered models, in vitro systems, etc.) to improve sensitivity. In this article we briefly review the workshop’s outcome and outline some next steps forward in pursuing the workshop’s recommendations. Breakout group reports and additional information on the workshop, including participants, presentations, public comments and background materials, are posted on the NTP website

Identifying the PECO:A framework for formulating good questions to explore the association of environmental and other exposures with health outcomes

[First paragraph] A clearly-framed question creates the structure and delineates the approach to defining research objectives, conducting systematic reviews and developing health guidance (Guyatt et al., 2011; Armstrong et al., 2007). To assess the association between exposures and outcomes, including in the field of nutrition, environmental and occupational health, the concept of defining the Population (including animal species), Exposure, Comparator, and Outcomes (PECO) as pillars of the question is increasingly accepted (Morgan et al., 2016; Morgan et al., n.d.). Thus, the PECO defines the objectives of the review or guideline. Furthermore, the PECO informs the study design or inclusion and exclusion criteria for a review, as well as facilitating the interpretation of the directness of the findings based on how well the actual research findings represent the original question

Polyfluoroalkyl Chemicals and Menopause among Women 20-65 Years of Age (NHANES)

Background: Polyfluoroalkyl chemicals (PFCs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have been associated with early menopause. However, previous cross-sectional studies have lacked adequate data to investigate possible reverse causality (i.e., higher serum concentrations due to decreased excretion after menopause)

Still moving toward automation of the systematic review process: a summary of discussions at the third meeting of the International Collaboration for Automation of Systematic Reviews (ICASR)

The third meeting of the International Collaboration for Automation of Systematic Reviews (ICASR) was held 17–18 October 2017 in London, England. ICASR is an interdisciplinary group whose goal is to maximize the use of technology for conducting rapid, accurate, and efficient systematic reviews of scientific evidence. The group seeks to facilitate the development and widespread acceptance of automated techniques for systematic reviews. The meeting’s conclusion was that the most pressing needs at present are to develop approaches for validating currently available tools and to provide increased access to curated corpora that can be used for validation. To that end, ICASR’s short-term goals in 2018–2019 are to propose and publish protocols for key tasks in systematic reviews and to develop an approach for sharing curated corpora for validating the automation of the key tasks