Abstract Title:

Male reproductive toxicity of four bisphenol antioxidants in mice and rats and their estrogenic effect.

Abstract Source:

Arch Toxicol. 2006 Apr;80(4):225-41. PMID: 16231125

Abstract Author(s):

Osamu Takahashi, Shinshi Oishi

Article Affiliation:

Department of Toxicology. Tokyo Metropolitan Research Laboratory of Public Health, 24-1, Hyakunincho 3-chome, 169-0073 Shinjuku-ku, Tokyo, Japan. [email protected]

Abstract:

Male mice and rats were fed a diet containing four bisphenol antioxidants, 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (ME), 2,2'-methylenebis(4-methyl -6-tert-butylphenol) (MM), 4,4'-butylidenebis(3-methyl-6-tert-butylphenol) (BM), or 4,4'-thiobis(3-methyl-6-tert-butylphenol) (TM) at levels of 0.06-0.25% for 2 months. BM and TM decreased epididymal, seminal vesicular, prostate and preputial weights, and injured seminiferous tubules in mice in a dose-dependent fashion. BM and TM also reduced sex accessory organ weights and sperm production capacity in rats, but MM and ME were more toxic to rats than BM and TM. ME and MM did not bind ERalpha up to 10(-3) M, while BM and TM competitively bound ERalpha against beta-estradiol (E2). Fifty percent inhibitory concentrations (IC50 s) of BM, TM, and bisphenol A (positive control) against E2-binding were 7.3 x 10(-6) M, 1.8 x 10(-5) M, and 1.4 x 10(-5) M, respectively. When ovariectomized (OVX) mice were sc administered TM at doses of 60 and 300 mg/kg/day for 4 days, or when OVX mice were fed BM in the diet at a level of 0.25% for 2 months, uterine weight was significantly increased. These results suggest that BM and TM are weakly toxic, possibly through an estrogenic mechanism to male reproductive organs in mice as well as rats, while MM and ME may be the direct testicular toxins in rats but not mice.

Study Type : Animal Study
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