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      Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007)

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          Abstract

          Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association.

          Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure.

          Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic.

          Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.

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          Most cited references 52

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          Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses.

           T. Hayes,  A. Collins,  M. Lee (2002)
          Atrazine is the most commonly used herbicide in the U.S. and probably the world. It can be present at several parts per million in agricultural runoff and can reach 40 parts per billion (ppb) in precipitation. We examined the effects of atrazine on sexual development in African clawed frogs (Xenopus laevis). Larvae were exposed to atrazine (0.01-200 ppb) by immersion throughout larval development, and we examined gonadal histology and laryngeal size at metamorphosis. Atrazine (> or =0.1 ppb) induced hermaphroditism and demasculinized the larynges of exposed males (> or =1.0 ppb). In addition, we examined plasma testosterone levels in sexually mature males. Male X. laevis suffered a 10-fold decrease in testosterone levels when exposed to 25 ppb atrazine. We hypothesize that atrazine induces aromatase and promotes the conversion of testosterone to estrogen. This disruption in steroidogenesis likely explains the demasculinization of the male larynx and the production of hermaphrodites. The effective levels reported in the current study are realistic exposures that suggest that other amphibian species exposed to atrazine in the wild could be at risk of impaired sexual development. This widespread compound and other environmental endocrine disruptors may be a factor in global amphibian declines.
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            Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis).

            The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.
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              Use of agricultural pesticides and prostate cancer risk in the Agricultural Health Study cohort.

              The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed.
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                Author and article information

                Journal
                Environ Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                27 May 2011
                September 2011
                : 119
                : 9
                : 1253-1259
                Affiliations
                [1 ]Division of Cancer, Epidemiology, and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
                [2 ]Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
                [3 ]Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
                [4 ]National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA
                Author notes
                Address correspondence to L. Beane Freeman, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 8112, MSC 7240, Bethesda, MD 20892 USA. Telephone: (301) 451-8793. Fax: (301) 402-1819. E-mail: freemala@ 123456mail.nih.gov
                [*]

                Current address: 1412 Harmony Lane, Annapolis, MD 21409 USA

                Article
                ehp.1103561
                10.1289/ehp.1103561
                3230407
                21622085

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research

                Public health

                agriculture, atrazine, epidemiology, cancer, cohort study, pesticide

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