ASSESSING ENVIRONMENTAL CHEMICALS FOR ESTROGENICITY USING A COMBINATION OF IN-VITRO AND IN-VIVO ASSAYS

Because of rampant concern that estrogenic chemicals in the environmen t may be adversely affecting the health of humans and wildlife, reliab le methods for detecting and characterizing estrogenic chemicals are n eeded. It is important that general agreement be reached on which test s to use and that these tests then be applied to the testing of both m an-made and naturally occurring chemicals. As a step toward developing a comprehensive approach to screening chemicals for estrogenic activi ty, three assays for detecting estrogenicity were conducted on 10 chem icals with known or suspected estrogenic activity. The assays were 1) competitive binding with the mouse uterine estrogen receptor, 2) trans criptional activation in HeLa cells transfected with plasmids containi ng an estrogen receptor and a response element, and 3) the uterotropic assay in mice. The chemicals studied were 17 beta-estradiol, diethyls tilbestrol, tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxych lor metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), endosulfan, nonylphenol, o,p'-DDT, and kepone. These studies were cond ucted to assess the utility of this three-assay combination in the rou tine screening of chemicals, or combinations of chemicals, for estroge nic activity. Results were consistent among the three assays with resp ect to what is known about the estrogenic activities of the chemicals tested and their requirements for metabolic activation. By providing i nformation on three levels of hormonal activity (receptor binding, tra nscriptional activation, and an in vivo effect in an estrogen-responsi ve tissue), an informative profile of estrogenic activity is obtained with a reasonable investment of resources.