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.

1 Follower
47 Reads
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Archives of Toxicology 07/2015; DOI:10.1007/s00204-015-1554-1 · 5.98 Impact Factor
  • Source
    • "acute or long-term OP exposure, ranging from respiratory failure (Baldi et al., 2014) to neuropsychiatric disorders (Mackenzie Ross et al., 2010) and teratogenic or carcinogenic effects (Vakonaki et al., 2013). In this regard, a need became evident to utilize tools that enable a reliable, relevant risk assessment or biomonitoring of susceptibility of human populations exposed to OP (Burns et al., 2013; Li et al., 2012). Human paraoxonase-1 (PON1; EC is a glycosylated enzyme that is associated with high-density lipoproteins in the blood. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Paraoxonase 1 (PON1) is a glycosylated enzyme that is found associated with high-density lipoproteins in blood. In addition to its endogenous antioxidant role, this enzyme is also involved in hydrolysis of organophosphate (OP) pesticides in plasma. PON1 activity shows great variability in the population as a result of a polymorphism in the coding sequence that is expressed as a Glu(Q)/Arg(R) substitution at position 192 of the amino acid sequence. The aim of this study was to determine the activity levels (phenotype) and genotype of PON1 in a group of 85 agricultural workers occupationally exposed to OP pesticides and compared to 97 control subjects without occupational exposure. Allelic and genotypic frequencies of PON1Q192R polymorphism, as well as their catalytic activities, were established for the first time in a group of agricultural Chilean workers. The Q allele was more frequently represented in our studied population (approximately 60%). The Q allele is less efficient than the R allele at metabolizing chlorpyrifos (CPF), the most widely used OP pesticide in the geographical areas where samples were obtained. Further, a large interindividual variability in PON1 activity was observed, suggesting wide variation of individual susceptibility to CPF, an issue that needs to be considered in human monitoring studies.
    Journal of Toxicology and Environmental Health Part A 03/2015; 78(6):357. DOI:10.1080/15287394.2014.982843 · 2.35 Impact Factor
  • Source
    • "" Despite more than five decades of research, and thousands of studies published to date on a wide array of chemicals, it is often impossible to draw robust conclusions about the presence or absence of causal links between specific environmental exposures and human health. Many systematic assessments of epidemiological evidence stop short of supporting or refuting causal hypotheses at least in part due to interstudy heterogeneity regarding design, methods, and reporting (Burns et al. 2013; Corsini et al. 2013; Gallagher and Meliker 2010; Gascon et al. 2013; Goodman et al. 2010; 2014; González- Alzaga et al. 2013; Koyashiki et al. 2010; LaKind et al. 2014a; Maull et al. 2012; McGwin et al. 2010; Olsen et al. 2009; Schoeman et al. 2009 "
    [Show abstract] [Hide abstract]
    ABSTRACT: In observational research, evidence is usually derived from multiple studies, and any single result is rarely considered sufficient for public health decision making. Despite more than five decades of research and thousands of studies published, the ability to draw robust conclusions regarding the presence or absence of causal links between specific environmental exposures and human health remains limited. To develop policies that are protective of public health and can withstand scrutiny, agencies need to rely on investigations of satisfactory quality that follow sufficiently concordant protocols in terms of exposure assessment, outcome ascertainment, data analysis, and reporting of results. Absent such concordance, the ability of environmental epidemiology studies to inform decision making is greatly diminished. Systems and tools are proposed here to improve concordance among environmental epidemiology studies. Specifically, working systems in place in other fields of research are critically examined and used as guidelines to develop analogous policies and procedures for environmental epidemiology. A three-part path forward toward more concordant, transparent, and readily accessible environmental epidemiology evidence that parallels ongoing efforts in medical research is proposed. The three parts address methods for improving quality and accessibility of systematic reviews, access to information on ongoing and completed studies, and principles for reporting. The goals are to increase the value of epidemiological research in public health decision making and to stimulate discussions around solutions proposed herein.
    Journal of Toxicology and Environmental Health Part B 02/2015; 18(2):105-20. DOI:10.1080/10937404.2015.1051612 · 4.97 Impact Factor
Show more


47 Reads
Available from