Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

a The Dow Chemical Company , Midland , Michigan , USA.
Journal of Toxicology and Environmental Health Part B (Impact Factor: 4.97). 04/2013; 16(3-4):127-283. DOI: 10.1080/10937404.2013.783383
Source: PubMed


Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective and tiered approaches in animal testing are discussed.

    • "1339 conducted to identify occupational and environmental exposures among individuals residing or working on farms that might influence risk of cancer development (Blair and Beane Freeman, 2009; Alavanja and Bonner, 2012) or other health endpoints such as respiratory diseases (American Thoracic Society [ATS], 1998; May et al., 2012 ) and neurodevelopmental effects (London et al., 2012; Burns et al., 2013). Specific exposures that have been assessed include pesticides, endotoxin and other bioaerosols, zoonotic viruses and other bloodborne pathogens, solvents, welding fumes, and diesel exhaust (Blair and Beane Freeman, 2009). "
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    ABSTRACT: Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.
    No preview · Article · Nov 2015 · Journal of Toxicology and Environmental Health Part A
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    • "In order to protect crops, farmers often apply pesticides at regular intervals, potentially resulting in accumulation of considerable amounts of residues in the final products. Pesticides deposited during plant protection operations are a major global concern today, and residues are strictly monitored especially in commodities for export aqs these chemicals may produce adverse effects (Burns et al. 2013; Wolansky and Tornero-Velez 2013; Malhat, Watanabe, and Youssef 2015). The excessive use/misuse results in widespread environmental contamination manifested as adverse health problems to consumers and local and global environmental impacts (Malhat and Hassan 2011; Malhat and Nasr 2012; Vazquez-Boucard et al. 2014). "
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    ABSTRACT: A high performance liquid chromatography with photodiode array detector (HPLC-DAD) analytical method was developed to determine the residue levels and investigates the dissipation pattern and safety use of flusilazole in grape. The results showed that the average recoveries were in the range of 86–90%. Limits of detection (LOD) and quantification (LOQ) were 0.008 and 0.02 mg/kg, respectively. The residue levels of flusilazole were best described to first order rate kinetics and with half-lives ranged from 4.2 (recommended dose) to 4.6 days (double the recommended dose). In conclusion; flusilazole at the recommended or even at double the recommended doses does not pose any hazards to consumers.
    Full-text · Article · Aug 2015 · Toxicological and Environmental Chemistry
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    • "While simple in vitro screening assays are useful for probing targeted receptor–ligand interactions, these screens fail to take into account the complexity of the vertebrate nervous system and will miss chemicals that modify nervous system function in novel ways. A phenotype-based screen is needed to identify developmental neuromodulatory compounds in the absence of specific targets (Burns et al. 2013; Selderslaghs et al. 2013). Designing in vivo phenotypic screens in a high-throughput manner would provide the ability to discover complex behavioral phenotypes using whole organisms, where the full gamut of coordinated events leading to nervous system development occurs, including cellular differentiation, proliferation, migration, synapse formation, and apoptosis (Makris et al. 2009; Padilla et al. 2012; Sanes et al. 2005; Truong et al. 2014). "
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    ABSTRACT: New strategies are needed to address the data gap between the bioactivity of chemicals in the environment versus existing hazard information. We address whether a high-throughput screening (HTS) system using a vertebrate organism (embryonic zebrafish) can characterize chemical-elicited behavioral responses at an early, 24 hours post-fertilization (hpf) stage that predict teratogenic consequences at a later developmental stage. The system was used to generate full concentration-response behavioral profiles at 24 hpf across 1060 ToxCast™ chemicals. Detailed, morphological evaluation of all individuals was performed as experimental follow-up at 5 days post-fertilization (dpf). Chemicals eliciting behavioral responses were also mapped against external HTS in vitro results to identify specific molecular targets and neurosignalling pathways. We found that, as an integrative measure of normal development, significant alterations in movement highlighted active chemicals representing several modes of action. These early behavioral responses were predictive for 17 specific developmental abnormalities and mortality measured at 5 dpf, often at lower (i.e., more potent) concentrations than those at which morphological effects were observed. Therefore, this system can provide rapid characterization of chemical-elicited behavioral responses at an early developmental stage that are predictive of observable adverse effects later in life.
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