Immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals

Abstract

We performed an immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30 chemicals to assess the relationship between the results of two assays. The chemicals tested by the uterotopic assay were 4-n-amylphenol, p-dodecyl-phenol, p-(tert-pentyl)phenol, 4-cyclohexylphenol, 4-(1-adamantyl)phenol, 4,4′-thiobis-phenol, diphenyl-p-phenylenediamine, 4-hydroxyazobenzene, 4-(phenylmethyl)phenol, 4,4′-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4,4′-dihydroxybenzophenone, 2,2′,4,4′-tetrahydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4′-trihydroxybenzophenone, testosterone enanthate, and methyltestosterone. The chemicals tested by the Hershberger assay were the 18 chemicals tested in the uterotrophic assay plus the following: 17alpha estradiol, estrone, equilin, norethindrone, norgestrel, ethynyl estradiol, bisphenol A, bisphenol B, bisphenol F, 4-tert-octylphenol, p-cumyl phenol, and nonylphenol. All chemicals examined in this study were positive in a reporter gene assay for ER-alpha. In the immature rat uterotrophic assay, all chemicals induced uterotrophy and p-(tert-pentyl)phenol, 4,4′-thiobis-phenol, 4-(phenylmethyl)phenol, 4,4′-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4′-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4,4′-dihydroxybenzophenone, 2,2′,4,4′-tetrahydroxybenzophenone, 4-hydroxybenzophenone, and 2,4,4′-trihydroxybenzophenone exerted both estrogen agonistic effect and reduced the estrogenic effect of ethynylestradiol. In the Hershberger assay, a clear androgen agonistic effect was detected in the androgen derivatives testosterone enanthate and methyltestosterone.