Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4 -[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols.
We performed an uterotrophic assay, the Hershberger assay, and a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) of 4,4 -[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and the uterine weight of rats given the 1,000 mg/kg dose of the test chemical plus ethinyl estradiol decreased. In the Hershberger assay, the test chemical was orally administered at doses of 0, 100, 300, and 1,000 mg/kg day to castrated male SD rats for ten consecutive days beginning on postnatal day 56, and no changes were observed. On the other hand, when the test chemical was orally administered at doses 0, 100, 300, and 1,000 mg/kg day for at least 28 days, a decrease in LH values in rats of both sexes and a decrease in FSH and estradiol values in female rats were detected in the 1,000 mg/kg group, and abnormal estrous cycles, uterine glandular atrophy, persistence of ovarian corpora lutea, vaginal epithelial mucification, and mammary glandular hyperplasia were also observed in one female rat in the 1,000 mg/kg group. Therefore, the uterotrophic assay used in this study showed that the chemical has the estrogen-antagonist properties, and some potentially endocrine-mediated effects were detected in growing rats based on the results of the enhanced OECD test guideline No. 407. However, the changes were observed in rats given a high dose of the chemical, 1,000 mg/kg day.
Yamasaki
Kanji
K
Chemicals Evaluation and Research Institute, 3-822 Ishii, Hita, Oita, 877-0061, Japan. yamasaki-kanji@ceri.jp
Miyata
Katumi
K
Muroi
Takako
T
Ehara
Hatsune
H
Higashihara
Nobuhiko
N
Houshuyama
Satsuki
S
Oshima
Hiroshi
H
Minobe
Yasushi
Y
D000410:Alanine Transaminase / Q000097:blood; D000475:Alkenes / Q000633:toxicity*; D000818:Animals; D001681:Biological Assay; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010636:Phenols / Q000633:toxicity*; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains; D018675:Toxicity Tests; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology
C527688:4,4 -(1-(4-(1-(4-hydroxyphenyl)-1-methylethyl)phenyl)ethylidene)bis(phenol); D000475:Alkenes; D001786:Blood Glucose; D001798:Blood Proteins; D004965:Estrogen Antagonists; D010636:Phenols; D014280:Triglycerides; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D000410:Alanine Transaminase