Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos

Department of Molecular Biosciences, UC Davis School of Veterinary Medicine, Davis, CA 95618, USA.
NeuroToxicology (Impact Factor: 3.38). 01/2012; 33(4):660-8. DOI: 10.1016/j.neuro.2011.12.017
Source: PubMed


Translational research is needed to understand and predict the neurotoxic consequences associated with repeated occupational exposures to organophosphorus pesticides (OPs). In this report, we describe a research strategy for identifying biomarkers of OP neurotoxicity, and we characterize pesticide application workers in Egypt's Menoufia Governorate who serve as our anchor human population for developing a parallel animal model with similar exposures and behavioral deficits and for examining the influence of human polymorphisms in cytochrome P450 (CYP) and paraoxonase 1 (PON1) enzymes on OP metabolism and toxicity. This population has previously been shown to have high occupational exposures and to exhibit a broad range of neurobehavioral deficits. In addition to observational studies of work practices in the field, questionnaires on demographics, lifestyle and work practices were administered to 146 Egyptian pesticide application workers applying pesticides to the cotton crop. Survey results indicated that the application workforce uses standard operating procedures and standardized equipment provided by Egypt's Ministry of Agriculture, which provides a workforce with a stable work history. We also found that few workers report using personal protective equipment (PPE), which likely contributes to the relatively high exposures reported in these application workers. In summary, this population provides a unique opportunity for identifying biomarkers of OP-induced neurotoxicity associated with occupational exposure.

Download full-text


Available from: Diane Rohlman
  • Source
    • "First, therapeutic strategies for patients exposed to these toxics can be developed. Obviously, eliminating highly toxic pesticides is preferable to finding therapies for intoxications, but in a real-world scenario, availability of countermeasures can be of immediate benefit to those affected (Lein et al. 2012). Second, such studies and the resulting knowledge on toxicity ranking of compounds should allow legislators to create legal frameworks that encourage the use of pesticides with the least unfavorable toxicology profile. "

    Full-text · Article · Aug 2013 · Archives of Toxicology
  • Source
    • "Pesticides which were originally designed to target nervous system of insects can obviously also cause neurotoxicity to humans.[1234] Carbaryl (1-naphthyl methylcarbamate) is an acetyl cholinesterase inhibitor classified under carbamates group of pesticides. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroprotective effect of naringenin against carbaryl toxicity was studied in mouse neuroblastoma cell line. Mouse neuroblastoma cells (Neuro 2A) obtained from National Center for Cell Sciences, Pune, India were either exposed to carbaryl or pre-treated with naringenin (a flavonoid prepared from grape fruit) before their exposure to carbaryl. Results were analyzed using MTT [3-4,5-Dimethylthiazol-2-yl)-2,5-diphenltetrazolium bromide] assay for cell viability, FACS (fluorescence assisted cell sorting) analysis for apoptotic and necrotic cell populations, DCFH-DA (2`,7`-dichlorofluorescin-diacetate) assay for Reactive Oxygen Species (ROS) visualization, JC-1 staining for determining mitochondrial membrane potential and real-time PCR for quantifying pro and anti-apoptotic gene expression. Exposure to naringenin resulted in better survival of Neuro 2A cells which were subsequently subjected to carbaryl toxicity. Treatment with naringenin was found to reduce the oxidative stress by decreasing the ROS and was found to maintain the integrity of mitochondrial membrane potential. It was also found to downregulate pro-apoptotic genes (BAX and Caspase-3) while upregulating anti-apototic gene (Bcl2). The results of this pilot study underline the potential of naringenin in treating carbaryl induced neurotoxicity and further studies are warranted to establish the effect of naringenin in vivo conditions.
    Full-text · Article · Jul 2013 · Journal of Pharmacology and Pharmacotherapeutics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Risk assessment is used both formally and informally to estimate the likelihood of an adverse event occurring, for example, as a consequence of exposure to a hazardous chemical, drug, or other agent. Formal risk assessments in government regulatory agencies have a long history of practice. The precision with which risk can be estimated is inevitably constrained, however, by uncertainties arising from the lack of pertinent data. Developing accurate risk assessments for nanoparticles and nanoparticle-containing products may present further challenges because of the unique properties of the particles, uncertainties about their composition and the populations exposed to them, and how these may change throughout the particle's life cycle. This review introduces the evolving practice of risk assessment followed by some of the uncertainties that need to be addressed to improve our understanding of nanoparticle risks. Given the clarion call for life-cycle assessments of nanoparticles, an unprecedented degree of national and international coordination between scientific organizations, regulatory agencies, and stakeholders will be required to achieve this goal. WIREs Nanomed Nanobiotechnol 2013, 5:374–387. doi: 10.1002/wnan.1216 For further resources related to this article, please visit the WIREs website. This article is a U.S. Government work, and as such, is in the public domain in the United States of America. Disclaimer: This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. The approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
    Full-text · Article · Jul 2013 · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology
Show more