INTERACTIONS BETWEEN ENDOSULFAN AND DIELDRIN ON ESTROGEN-MEDIATED PROCESSES IN-VITRO AND IN-VIVO

There is growing concern that estrogenic chemicals, both natural and h uman-made, may be causing a variety of reproductive disorders in wildl ife and human populations. Recent in vitro data suggest that the inter action between some weakly estrogenic organochlorines, dieldrin, endos ulfan, toxaphene, and chlordane, causes a synergistic increase in thei r estrogenic potency, an effect due to joint action on estrogen recept ors (ER), As these studies were conducted using models of estrogen act ion derived from cells that are not physiologically controlled by estr ogens, the relevance of these findings to human health are not clear, The present studies were conducted to examine the interaction between endosulfan and dieldrin in the activation of ER in or extracted from m ammalian cells, Endosulfan and dieldrin showed no synergism in displac ing H-3-E-2 from rat uterine ER or in inducing the proliferation of MC F-7 breast cancer cells, an estrogen-dependent response. Furthermore, endosulfan (0.1 mg per animal per d) or dieldrin (0.1 mg), alone or in combination, injected intraperitoneally daily for 3 d, did not stimul ate any uterotrophic activity nor had any effect on pituitary prolacti n or other endocrine-related endpoints in immature female rats, These studies demonstrate that these weakly estrogenic compounds do not inte ract in a synergistic fashion in binding to ER or in activating ER-dep endent responses in mammalian tissues or cells, Thus, these results su ggest that coexposure to these weakly estrogenic environmental contami nants likely will not cause human reproductive toxicity related to est rogen action. (C) 1997 Elsevier Science Inc.