Reproductive effects of tris(4-chlorophenyl)methanol in the rat

Tris(4-chlorophenyl)methanol (TCPM) is a global contaminant of unknown orig in that is structurally related to the endocrine modulating pesticides 1,1, 1 -trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and Dicofol. Therefore, th e potential reproductive toxic effects of TCPM were investigated in sexuall y mature male Sprague Dawley rats (n = 20) treated with 1.0, 10.0 or 100 pp m of TCPM mixed in the diet for 28 days. The calculated TCPM intake was 0.0 , 0.1, 1.2 and 12.4 mg/kg/day, respectively. Serum concentrations of follic le stimulating hormone (FSH) in terminal blood samples were significantly ( P < 0.02) elevated in the highest dose group compared to the controls. In c ontrast, dietary exposure to TCPM had no effect on circulating levels of lu teinizing hormone (LH), testosterone (T) and the T/LH ratio. Incubation of MCF-7 cells with increasing concentrations of TCPM failed to either induce proliferation or to block the proliferative effect induced by estradiol ind icating that TCPM is neither estrogenic or anti-estrogenic. Relative bindin g affinity studies using androgen receptors from the prostate revealed that TCPM has a binding affinity comparable to 1,1-dichloro-2,2-bis(p-chlorophe nyl)ethylene (p,p'-DDE), the principle metabolite of DDT. In addition, the calculated Ki (0.62 mu M) for TCPM is lower than the reported Ki's for the antiandrogenic pesticides p,p'-DDE and vinclozolin. Although TCPM binds wit h the androgen receptor in vitro, the absence of both an effect on serum T levels and morphological changes in the testis suggests that the mechanism of action for elevated FSH levels seen in vivo may not involve an antiandro genic effect of TCPM at the dose level used in this study. The no adverse e ffect level for reproductive effects of TCPM is 10 ppm which is equivalent to a calculated intake of 1.2 mg/kg/day. (C) 1999 Elsevier Science Ltd. All rights reserved.