Comparative study of the uterotrophic potency of 14 chemicals in a uterotrophic assay and their receptor-binding affinity.
We performed an immature rat uterotrophic assay of 14 chemicals having various receptor-binding affinities in order to assess the relationship between their uterotrophic potency and receptor-binding affinity. The chemicals tested were phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, phthalic acid di-n-propyl ester, 2-ethylhexyl-p-hydroxybenzoate, 4,4'-biphenol, 4,4'-sulfonyldiphenol, 4,4'-dihydroxydiphenylmethane, 2,4-dihydroxybenzophenone, 4,4'-cyclohexylidenebisphenol, 4-t-butylpyrocatechol, clomiphene citrate, 4,4'-(1,3-phenylenediisopropylidene)bisphenol, p-t-butylphenol, and diallylterephthlate. Two of the 14 chemicals, phthalic acid di-n-propyl ester and diallylterephthlate, exhibited no receptor-binding affinity, and the receptor-binding affinity of phthalic acid di-n-hexyl ester and phthalic acid di-n-amyl ester was lower than that of the other chemicals. Ten of the chemicals showed uterotrophic potency, the exceptions being phthalic acid di-n-propyl ester, diallylterephthlate, phthalic acid di-n-hexyl ester, and phthalic acid di-n-amyl ester. The results of the present study demonstrate that the affinity of the chemicals in the receptor-binding assay correlated well with their potency in the uterotrophic assay except for a few chemicals with very low receptor-binding affinity.
Yamasaki
Kanji
K
Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822 Ishii, Hita, 877-0061 Oita, Japan. yamasaki-kanji@ceri.jp
Noda
Shuji
S
Imatanaka
Nobuya
N
Yakabe
Yoshikuni
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D017930:Genes, Reporter; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects*
D004967:Estrogens; D011960:Receptors, Estrogen; D004997:Ethinyl Estradiol