Estrogenic activity of selected anilines evaluated with a recombinant yeast assay

Suspected endocrine disrupters range from natural plant constituents (i.e., phytoestrogens) to industrial organic chemicals (i.e., xenoestrogens), including alkylphenols, bisphenols, polychlorinated biphenyls, and some pesticides. Several structural features are important for estrogenic activity, including a free benzene ring with a polar (e.g., hydroxy) group and a hydrophobic group. The present study was undertaken to explore the estrogenic activity of chemicals containing an amino group on the benzene ring instead of a hydroxy group. There is a great deal of chemical similarity between anilines and phenols, including close proximity in an 8- dimensional hyperspace describing the chemical universe and similar hydrogen-bonding properties. The chemicals chosen for the current study contain a benzene ring with an amino group in the para-position. The hydrophobic constituents of the compounds vary in size and shape to explore variations in potency due to the configuration of the hydrophobic group. The study consisted of the following aims: i) generate estrogenic activity and acute toxicity data for a group of 37 substituted anilines utilizing the Saccharomyces cerevisiae recombinant yeast assay, ii) calculate hazard indices for each of these chemicals, and iii) compare estrogenic activity between the present group of anilines and a set of previously tested, analogous phenols also tested in the yeast assay. The results indicate that anilines are less estrogenic than phenols, and that acute toxicity often precludes an aniline's ability to induce estrogenic activity. While the natural estrogen 17-β-estradiol is active in the 10^-10 range, the highest tested aniline had an EC₅₀ of 10^-8, a difference of four orders of magnitude. Because of their low estrogenicity and acute toxicity, therefore, anilines on average are only very weak environmental estrogens.