| Studies on the estrogenic activity of endosulfan in rodentsOccupational and Environmental Health, Zbejiang UniversityPostgraduate for Ph. D. Zhu Xinqiang Supervisors: Jiang Huai, Huang Xingshu, and Yukinori KusakaAbstractIt was reported that human sperm production has decreased by around 50% over the past 50 years, and the incidence of abnormalities of human male reproductive tracts, such as cryptorchidism and hypospadias, has almost doubled during the same period. There was also an increasing trend in endometriosis and some hormone-dependent tumors i.e. testicular, prostate, and breast cancers. Meanwhile, There was increasing evidence that the male reproductive system and fertility of some aquatic life and wildlife degenerated, which was found to be related to the contamination of some estrogenic chemicals in their living habitats. Therefore, It was hypothesized that the environmental estrogens may account for the disruptive effects on male reproductive system of the human as well as the wildlife. Although there are still a lot of controversy about these finding and hypothesis, the potential hazards of environmental estrogens and other endocrine disrupters on the environment and human health have brought a great deal of attention from the scientists, regulatory officials as well as the public. It was required by the U.S.PEA to screen and test the numerous existing chemicals for their potential endocrine disruptive effects. When a of chemical is found to be estrogenic or possessing other endocrine disruptive effects, risk reassessment should be made and regulatory measures should be taken, for example to ban or to restrict the use or to reduce the residue limit in food or environment.Increasing number of chemicals have been found to be estrogenic or possessing other endocrine disruptive effects. Among them are some organochlorine pesticides and other organochlorine chemicals, such as DDT and its metabolite p,p'-DDE, kepone, toxaphene, dieldrin, and PCBs, dioxins, and furans. Most of the organochlorine pesticides were banned or strictly restricted in almost all of the developed countries for their persistent contamination to the environment and accumulation in the body. Endosulfan, however, is one of thefour organochlorine pesticides that are still registered in use throughout the world including United States as well as China. It was estimated that around 1500~2000 tons technical product of endosulfan were produced in China per year. Simonich et al. reported that a global distribution of endosulfan was found recently and the endosulfan was the second high among the 22 organochlorine compounds investigated.Soto and his colleagues firstly reported that endosulfan has estrogenic effect as other organochlorine compounds on E-SCREEN test. This report aroused new interests to reassess its hazard to human health. A series of in vitro studies about the estrogenicity of endosulfan have been carried out, but the results were conflicting. In some of then were very weak estrogenic, in others were not. Because of the complexity of estrogenic effects and the limitation of the short-term assays, none of the existing screening assay alone can accurately identify and assess whether chemicals possess estrogenic activities or not. Therefore, a battery of assays, especially a battery of in vitro and in vivo bioassays were recommended to evaluate the estrogenicity of a particular chemical. Considering the merits of in vivo studies in biotransformation i.e. activation or inactivation, protein-binding such as sex hormone binding protein (SHBP), toxicokinetics, and more evaluative in hazard identification and risk assessment, we selected a battery of short-term and long-term in vivo studies, including uterotrophic assay in weaning mice and ovariectomized adult mice, an in vivo multiple endpoints assay, and a gestational and lactational exposure assay to identify the estrogenic effects of endosulfan on the offspring. Furthermore, the adverse effects of endosulfan on spermatogenesis and oxidative damage, and th...
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