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      On the rumors about the silent spring: review of the scientific evidence linking occupational and environmental pesticide exposure to endocrine disruption health effects Translated title: Rumores de uma primavera silenciosa: uma revisão das evidências científicas sobre a associação entre exposição ocupacional e ambiental a pesticidas e distúrbios endócrinos

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          Abstract

          Occupational exposure to some pesticides, and particularly DBCP and chlordecone, may adversely affect male fertility. However, apart from the therapeutic use of diethylstilbestrol, the threat to human reproduction posed by "endocrine disrupting" environmental contaminants has not been supported by epidemiological evidence thus far. As it concerns other endocrine effects described in experimental animals, only thyroid inhibition following occupational exposure to amitrole and mancozeb has been confirmed in humans. Cancer of the breast, endometrium, ovary, prostate, testis, and thyroid are hormone-dependent, which fostered research on the potential risk associated with occupational and environmental exposure to the so-called endocrine-disrupting pesticides. The most recent studies have ruled out the hypothesis of DDT derivatives as responsible for excess risks of cancer of the reproductive organs. Still, we cannot exclude a role for high level exposure to o,p'-DDE, particularly in post-menopausal ER+ breast cancer. On the other hand, other organochlorine pesticides and triazine herbicides require further investigation for a possible etiologic role in some hormone-dependent cancers.

          Translated abstract

          A exposição ocupacional a determinados pesticidas, particularmente ao DBCP e à clordecona, pode ter efeitos adversos sobre a fertilidade masculina. Entretanto, com exceção do uso terapêutico do dietil-estilbestrol, a ameaça à reprodução humana através da "desregulação endócrina" por contaminantes ambientais ainda não foi comprovada através de evidências epidemiológicas. A questão diz respeito a outros efeitos endócrinos descritos em animais experimentais, e apenas a inibição tireóide foi confirmada em seres humanos, após exposição ocupacional a amitrole e mancozeb. O fato de serem hormônio-dependentes os cânceres de mama, endométrio, ovário, próstata, testículos e tireóide motivou pesquisas sobre o risco potencial associado à exposição ocupacional e ambiental aos pesticidas conhecidos como "desreguladores endócrinos". Os estudos mais recentes descartaram a hipótese dos derivados do DDT como responsáveis pelo risco em excesso de câncer dos órgãos reprodutivos. Entretanto, não se pode excluir o papel da exposição elevada ao o,p'-DDE, particularmente no câncer de mama pós-menopáusica, positivo para receptores estrogênicos. Além disso, há necessidade de mais investigação sobre o possível papel etiológico de outros pesticidas organoclorados e herbicidas triazínicos em alguns cânceres hormônio-dependentes.

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          The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.

          Estrogens are defined by their ability to induce the proliferation of cells of the female genital tract. The wide chemical diversity of estrogenic compounds precludes an accurate prediction of estrogenic activity on the basis of chemical structure. Rodent bioassays are not suited for the large-scale screening of chemicals before their release into the environment because of their cost, complexity, and ethical concerns. The E-SCREEN assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effect of estrogens on their target cells as an end point. This quantitative assay compares the cell number achieved by similar inocula of MCF-7 cells in the absence of estrogens (negative control) and in the presence of 17 beta-estradiol (positive control) and a range of concentrations of chemicals suspected to be estrogenic. Among the compounds tested, several "new" estrogens were found; alkylphenols, phthalates, some PCB congeners and hydroxylated PCBs, and the insecticides dieldrin, endosulfan, and toxaphene were estrogenic by the E-SCREEN assay. In addition, these compounds competed with estradiol for binding to the estrogen receptor and increased the levels of progesterone receptor and pS2 in MCF-7 cells, as expected from estrogen mimics. Recombinant human growth factors (bFGF, EGF, IGF-1) and insulin did not increase in cell yields. The aims of the work summarized in this paper were a) to validate the E-SCREEN assay; b) to screen a variety of chemicals present in the environment to identify those that may be causing reproductive effects in wildlife and humans; c) to assess whether environmental estrogens may act cumulatively; and finally d) to discuss the reliability of this and other assays to screen chemicals for their estrogenicity before they are released into the environment.
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            Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.

            The increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. The results suggest that abnormalities in male sex development induced by p,p'-DDE and related environmental chemicals may be mediated at the level of the androgen receptor.
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              Uses of ecologic analysis in epidemiologic research.

              Despite the widespread use of ecologic analysis in epidemiologic research and health planning, little attention has been given by health scientists and practitioners to the methodological aspects of this approach. This paper reviews the major types of ecologic study designs, the analytic methods appropriate for each, the limitations of ecologic data for making causal inferences and what can be done to minimize these problems, and the relative advantages of ecologic analysis. Numerous examples are provided to illustrate the important principles and methods. A careful distinction is made between ecologic studies that generate or test etiologic hypotheses and those that evaluate the impact of intervention programs or policies (given adequate knowledge of disease etiology). Failure to recognize this difference in the conduct of ecologic studies can lead to results that are not very informative or that are misinterpreted by others.
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                Author and article information

                Journal
                csp
                Cadernos de Saúde Pública
                Cad. Saúde Pública
                Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz (Rio de Janeiro, RJ, Brazil )
                0102-311X
                1678-4464
                April 2002
                : 18
                : 2
                : 379-402
                Affiliations
                [01] Cagliari orgnameUniversità degli Studi di Cagliari orgdiv1Facoltà di Medicina e Chirurgia orgdiv2Dipartimento di Igiene e Sanitá Publica Italia
                Article
                S0102-311X2002000200003 S0102-311X(02)01800203
                10.1590/S0102-311X2002000200003
                ecee0f03-efb9-4b59-871c-4443411b1ab9

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 01 June 2001
                : 06 January 2001
                : 07 May 2001
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 175, Pages: 24
                Product

                SciELO Public Health

                Self URI: Full text available only in PDF format (EN)
                Categories
                Review

                Neoplasms,Antitiroidianos,Endocrine Disruptors,Praguicidas,Reproduction,Pesticides,Desreguladores Endócrinos,Antithyroid Agents,Neoplasias,Reprodução

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