Hoberman Alan M, Schreur David K, Leazer Tyra, Daston George P, Carthew Philip, Re Thomas, Loretz Linda, Mann Peter
Charles River Preclinical Services, Horsham, PA 19044, USA.
Birth Defects Res B Dev Reprod Toxicol. 2008 Apr;83(2):123-33. doi: 10.1002/bdrb.20153.
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, methyl- and butylparaben, to try to replicate these studies and thereby evaluate potential reproductive effects in male Wistar rats.
Diets containing 0, 100, 1000 or 10,000 ppm of either butyl- 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).
None of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects. Metabolism experiments of butylparaben indicate that it is rapidly metabolized by non-specific esterases to p-hydroxybenzoic acid and butanol, neither of which is estrogenic.
Exposure to methyl- or butylparaben in the diet for eight weeks did not affect any male reproductive organs or parameters at exposures as high as 10,000 ppm, corresponding to a mean daily dose of 1,141.1+/-58.9 or 1,087.6+/-67.8 mg/kg/day for methyl- 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).
对羟基苯甲酸酯是化妆品和药品中广泛使用的防腐剂，并被批准用作食品添加剂。多年来，人们一直认为对羟基苯甲酸酯用于这些用途是安全的。最近，有报道称，从三周龄开始给大鼠口服对羟基苯甲酸酯8周后，会对雄性生殖参数产生不利影响。我们的研究使用了两种具有代表性的对羟基苯甲酸酯，即甲基对羟基苯甲酸酯和丁基对羟基苯甲酸酯，试图重复这些研究，从而评估对雄性Wistar大鼠的潜在生殖影响。
将含有0、100、1000或10000 ppm丁基或甲基对羟基苯甲酸酯的饲料喂给雄性大鼠8周。暴露开始时大鼠为22日龄。评估的参数包括器官重量、生殖组织的组织病理学、精子产生、活力、形态以及生殖激素水平（仅丁基对羟基苯甲酸酯）。
两种对羟基苯甲酸酯评估的所有参数均未显示出化合物或剂量依赖性的不利影响。丁基对羟基苯甲酸酯的代谢实验表明，它会被非特异性酯酶迅速代谢为对羟基苯甲酸和丁醇，这两种物质均无雌激素活性。
在饮食中暴露于甲基或丁基对羟基苯甲酸酯8周，在高达10000 ppm的暴露水平下，并未影响任何雄性生殖器官或参数，甲基和丁基对羟基苯甲酸酯的平均每日剂量分别为1141.1±58.9或1087.6±67.8 mg/kg/天。酯酶对对羟基苯甲酸酯的快速代谢可能解释了为什么这些弱雌激素物质通过相关暴露途径（即局部和口服）给药时不会产生体内效应。
