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Kevin Gaido,¹ Linda Dohme,¹ Fan Wang,² Ichen Chen,²
Barry Blankvoort,² Kavita Ramamoorthy,² and Stephen Safe²

¹Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina;
²Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas

Abstract

The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by nonadditive interactions between different endocrine-mediated responses. This study focused on estrogenic chemicals in the diet and compared the relative potencies or estrogen equivalents (EQs) of the daily consumption of xenoestrogenic organochlorine pesticides in food (2.44 µg/day) with the EQs in a single 200-ml glass of red cabernet wine. The reconstituted organochlorine mixture contained 1,1,1-trichloro-2-(p-chlorophenyl) -2-(o-chlorophenyl) ethane, 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene, endosulfan-1, endosulfan-2, p,p´-methoxychlor, and toxaphene ; the relative proportion of each chemical in the mixture resembled the composition reported in a recent U.S. Food and Drug Administration market basket survey. The following battery of in vitro 17ß-estradiol (E₂) -responsive bioassays were utilized in this study: competitive binding to mouse uterine estrogen receptor (ER) ; proliferation in T47D human breast cancer cells ; luciferase (Luc) induction in human HepG2 cells transiently cotransfected with C3-Luc and the human ER, rat ER-, or rat ER-ß ; induction of chloramphenicol acetyltransferase (CAT) activity in MCF-7 human breast cancer cells transfected with E₂-responsive cathepsin D-CAT or creatine kinase B-CAT plasmids. For these seven in vitro assays, the calculated EQs in extracts from 200 ml of red cabernet wine varied from 0.15 to 3.68 µg/day. In contrast, EQs for consumption of organochlorine pesticides (2.44 µg/day) varied from nondetectable to 1.24 ng/day. Based on results of the in vitro bioassays, organochlorine pesticides in food contribute minimally to dietary EQ intake. -- Environ Health Perspect 106(Suppl 6) :1347-1351 (1998) .

http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-6/1347-1351gaido/abstract.html

Key words: estrogenic activity, bioassays, wine extracts, organochlorine pesticide mixtures