Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic

The inadvertent estrogenicity of certain synthetic chemicals, and their sub sequent effects on the endocrine system of humans and wildlife, is of conce rn. In this paper we report findings from in vitro and in vivo (uterotrophi c) studies which confirm that a range of alkyl hydroxy benzoate preservativ es (parabens) are weakly estrogenic. In a receptor-binding assay, butylpara ben was able to compete with H-3-estradiol for binding to the rat estrogen receptor with an affinity approximately 5 orders of magnitude lower than th at of diethylstilboestrol, and between 1 and 2 orders of magnitude less tha n nonylphenol. In an in vitro yeast-based estrogen assay, the four most wid ely used parabens (namely methyl-, ethyl-, propyl-, and butylparaben) were all found to be weakly estrogenic with the most potent (butylparaben) being 10,000-fold less potent than 17 beta-estradiol. The estrogenic activity of parabens was inhibited by 4-hydroxy tamoxifen in vitro, illustrating the r equirement of these chemicals to interact with the estrogen receptor in ord er to activate the yeast, When administered orally to immature rats, the pa rabens were inactive. However, subcutaneous administration of butylparaben produced a positive uterotrophic response in viva, although it was approxim ately 100,000 times less potent than 17 beta-estradiol. Given their use in a wide range of commercially available topical preparations, it is suggeste d that the safety in use of these chemicals should be reassessed, with part icular attention being paid to estimation of the actual levels of systemic exposure of humans exposed to these chemicals. The acquisition of such data is a prerequisite to the derivation of reliable estimates of the possible human risk of exposure to parabens. (C) 1998 Academic Press.