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      Association of Pesticide Exposure with Neurologic Dysfunction and Disease

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          Abstract

          Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease.

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          Most cited references124

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          Health effects of chronic pesticide exposure: cancer and neurotoxicity.

          Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers.
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            Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat.

            Environmental toxicants and, in particular, pesticides have been implicated as risk factors in Parkinson's disease (PD). The purpose of this study was to determine if selective nigrostriatal degeneration could be reproduced by systemic exposure of mice to the widely used herbicide paraquat. Repeated intraperitoneal paraquat injections killed dopaminergic neurons in the substantia nigra (SN) pars compacta, as assessed by stereological counting of tyrosine hydroxylase (TH)-immunoreactive and Nissl-stained neurons. This cell loss was dose- and age-dependent. Several lines of evidence indicated selective vulnerability of dopaminergic neurons to paraquat. The number of GABAergic cells was not decreased in the SN pars reticulata, and counting of Nissl-stained neurons in the hippocampus did not reveal any change in paraquat-treated mice. Degenerating cell bodies were observed by silver staining, but only in the SN pars compacta, and glial response was present in the ventral mesencephalon but not in the frontal cortex and cerebellum. No significant depletion of striatal dopamine followed paraquat administration. On the other hand, enhanced dopamine synthesis was suggested by an increase in TH activity. These findings unequivocally show that selective dopaminergic degeneration, one of the pathological hallmarks of PD, is also a characteristic of paraquat neurotoxicity. The apparent discrepancy between pathological (i.e., neurodegeneration) and neurochemical (i.e., lack of significant dopamine loss) effects represents another important feature of this paraquat model and is probably a reflection of compensatory mechanisms by which neurons that survive damage are capable of restoring neurotransmitter tissue levels.
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              Environmental risk factors and Parkinson's disease: a case-control study in Taiwan.

              To explore environmental risk factors for Parkinson's disease (PD) in Taiwan, we investigated 120 patients with PD and 240 hospital control subjects matched with patients on age (+/-2 years) and sex. Based on a structured open-ended questionnaire, we carried out standardized interviews to obtain history of exposure to environmental factors, including place of residence, source of drinking water, and environmental and occupational exposures to various agricultural chemicals. In the univariate analysis, the history of living in a rural environment, farming, use of herbicides/pesticides, and use of paraquat were associated with an increased PD risk in a dose-response relationship. After adjustment for multiple risk factors through conditional logistic regression, the biological gradient between PD and previous uses of herbicides/pesticides and paraquat remained significant. The PD risk was greater among subjects who had used paraquat and other herbicides/pesticides than those who had used herbicides/pesticides other than paraquat. There were no significant differences in occupational exposures to chemicals, heavy metals, and minerals between PD patients and matched control subjects. The duration of drinking well water and alcohol consumption was not significantly associated with PD. There was an inverse relationship between cigarette smoking and PD. Environmental factors, especially exposures to paraquat and herbicides/pesticides, may play important roles in the development of PD in Taiwan.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institue of Environmental Health Sciences
                0091-6765
                June 2004
                20 May 2004
                : 112
                : 9
                : 950-958
                Affiliations
                National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
                Author notes
                Address correspondence to F. Kamel, Epidemiology Branch, MD A3-05, NIEHS Box 12233, Research Triangle Park, NC 27709. Telephone: (919) 541-1581. Fax: (919) 541-2511. E-mail: kamel@niehs.nih.gov

                We appreciate the thoughtful comments of D. Baird and M. Longnecker on an earlier version of this paper.

                This work was supported by internal funding to the Epidemiology Branch, NIEHS.

                The authors declare they have no competing financial interests.

                Article
                ehp0112-000950
                10.1289/ehp.7135
                1247187
                15198914
                ce3f0555-d0b0-4f67-b6ac-6033e579cbab
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 30 March 2004
                : 19 May 2004
                Categories
                Research Article
                Reviews

                Public health
                neurologic symptoms,pesticide,parkinson disease,fungicide,fumigant,organophosphate,insecticide,neurodegenerative disease,neurobehavioral performance

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