TRIPHENYLTIN AS A POTENTIAL HUMAN ENDOCRINE DISRUPTOR

Abstract

Organotin compounds have been implicated as reproductive toxicants and endocrine disruptors primarily through studies in aquatic organisms, with little information available in mammals. Among the organotins, aryltins have been less studied than alkyltins. Extensive data is available on mammalian developmental and reproductive toxicity of one aryltin compound, triphenyltin (TPT), from toxicity studies conducted in connection with the registration of triphenyltin hydroxide (TPTH) as a pesticide and supporting publications from the open literature. Indications of adverse functional and morphological effects on the reproductive tract of rats were reported in a dose range of 1.4–20mg/kg/d. Gonadal histopathology (both ovaries and testes) and infertility were affected at the higher doses, while reproductive-tract cancer, smaller litter sizes, and reproductive organ weights were affected at the lower end of the dose range. In vitro studies indicate that TPT can directly activate androgen receptor-mediated transcription and inhibit enzymes that are involved in steroid hormone metabolism. These data suggest that the aryltin TPT can be active as a reproductive toxicant in mammals and may be a human endocrine disruptor.

Opinions expressed are those of the authors and do not represent those of the California Environmental Protection Agency or the U.S. Environmental Protection Agency.

Notes

^a Dose estimated in study report; rounded average of male and female.

^b Three litters observed; 1 dam observed to have vaginal bleeding, no pups observed.

^c Statistically different from controls (p< .001).

^{d d} Statistically different from controls (p< .05).

^a Not evaluated statistically.

^b Duplicate control groups were included in the study.

^c Statistically different from controls (p??.01).

^d Statistically different from controls (p??.05).

^a Group mean; variability measures not provided in report.

^b Number of rats.

^c Significant at p < .05.

^a Kaplan-Meier survival statistics, no group effects.

^b Statistics and variability not provided for overall study mean; the majority of weekly means for the high-dose group were statistically different from controls.

^c Significant at p < .01, one-tailed trend test.

^d Significant at p < .001, one-tailed trend test.

^a Group mean; variability measure not provided in the report.

^b By t-test compared to controls, significant at p < .05.

^c Significant at p < .01.

^d Significant at p < .0001.

^a Mean number of follicles; variability measure not provided in the report.

^b Significantly different from control, ANOVA with LSD comparisons.

^a Doses as reported in the experiment or calculated as using standard assumptions as described in footnote to text.

∗ The authors reviewed the pesticide registration database in connection with preparation of a U.S. EPA Reregistration Eligibility Decision document (U.S. EPA, 1999) (JD) and the listing of TPTH as a reproductive toxicant under California's Proposition 65 (MG).

∗ The mg/kg/d doses were calculated by the authors based on the standard assumption that daily food consumption of rats is 5% of their body weight, and daily food consumption of mice is 10% of their body weight.