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: 3.9). 04/2013; 16(3-4):127-283. DOI: 10.1080/10937404.2013.783383
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aquatic monitoring is an important tool for identifying potential compounds in rivers that may damage the environment. Here, we evaluate the potential genotoxic effects of water samples from São Francisco River (Brazil) using the micronuclei (MN) assay in resident species, Astyanax paranae. Four seasonal collections occurred between the years 2009 and 2010, at three locations between two nearby cities in the region. It was clearly observed an increase of MN frequency in fish caught in the river. This result is most likely due to the sewage contamination from the treatment plant, the waste pesticides from crops and the lack of riparian vegetation along the river, especially during the winter when there was a significant increase in the frequencies of MN. These results indicate that compounds in waters from São Francisco River may have genotoxic effects and consequently, cause damage to the environment as well as to human health.
    Bulletin of Environmental Contamination and Toxicology 05/2014; 93(3). · 1.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment.
    NeuroToxicology 09/2014; · 3.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Butachlor is a chloroacetamide herbicide widely used in Asia, and may enter the aquatic environment through agricultural application. In this study, plasma VTG and hormone levels (E2, 11-KT, T3 and T4) were determined after the female rare minnow (Gobiocypris rarus) was exposed to butachlor at environmental relevant concentrations (0, 0.1, 1, and 10 μg/L) for 40 days. The mRNA levels of the HPG axis-related genes (gnrh, erα, vtg, star, lhr, 3β-hsd, cyp11a, cyp17, cyp19a and cyp19b), and the HPT axis-related genes (trα, dio1, dio2, and dio3) were quantified after 20 and 40 days exposure to butachlor. For the HPG axis, the plasma 11-KT was increased at exposure concentration of 10 μg/L, and VTG was significantly decreased at 1 μg/L. Functional genes like gnrh and cyp19b in the brains, star, lhr, cyp11a, 3β-hsd, and cyp19a in the ovaries, and erα and vtg in livers were up-regulated. For the HPT axis, the results showed that plasma T4 levels were significantly increased, the gene expression of dio1 was up-regulated, dio2 showed no significant variation, and dio3 was down-regulated in the livers. These results indicated that butachlor may promote the accumulation of T4 in fish through inactive deiodinase type 3. The transcription of HPG axis-related genes could serve as an auto-regulation of hormone levels after exposure to butachlor. Furthermore, the activation of gnrh may play an important role as a feed-back mechanism in the regulation of hormone levels and crosstalk of endocrine axes.
    Chemico-Biological Interactions 08/2014; · 2.98 Impact Factor


Available from