Abstract
BACKGROUND: Parabens are widely used preservatives in cosmetics and pharmaceutical products, and approved as food additives. Parabens have been considered safe for these uses for many years. Recently, adverse effects on male reproductive parameters in rats have been reported when parabens were given orally for 8 weeks starting at three weeks of age. Our studies used two representative parabens, methylโ and butylparaben, to try to replicate these studies and thereby evaluate potential reproductive effects in male Wistar rats. METHODS: Diets containing 0, 100, 1000 or 10,000โppm of either butylโ or methylparaben were fed to male rats for eight weeks. Rats were 22 days of age at the start of exposure. Parameters evaluated included organ weights, histopathology of reproductive tissues, sperm production, motility, morphology and reproductive hormone levels (butylparaben only). RESULTS: None of the parameters evaluated for either paraben showed compoundโ or dosageโdependent adverse effects. Metabolism experiments of butylparaben indicate that it is rapidly metabolized by nonโspecific esterases to pโhydroxybenzoic acid and butanol, neither of which is estrogenic. CONCLUSIONS: Exposure to methylโ or butylparaben in the diet for eight weeks did not affect any male reproductive organs or parameters at exposures as high as 10,000โppm, corresponding to a mean daily dose of 1,141.1ยฑ58.9 or 1,087.6ยฑ67.8โmg/kg/day for methylโ and butylparaben, respectively. The rapid metabolism of parabens by esterases probably explains why these weakly estrogenic substances elicit no in vivo effects when administered by relevant exposure routes (i.e., topical and oral). Birth Defects Research (Part B) 2008. 2008 WileyโLiss, Inc.