title: Endocrine-mediated effects of 4,4'-(hexafluoroisopropylidene)diphenol in SD rats, based on a subacute oral toxicity study.
abstract: The purpose of this study was to investigate the endocrine-mediated effects of 4,4'-(hexafluoroisopropylidene)diphenol according to OECD test guideline no. 407. The estrogenic properties of this chemical have already been shown on uterotrophic assay, and this chemical is classified as a low-production volume chemical in REACH program. Rats were orally gavaged with 0, 10, 30, and 100 mg/kg/day of test chemical for at least 28 days, beginning at 8 weeks of age. In the 100 mg/kg group of male rats, endocrine-mediated effects, atrophic changes in the mammary glands and testicular Leydig cells, decreased accessory sex organ weights, and hypertrophy of the adrenal zona fasciculata with increased organ weights were seen; there was dysfunction of the estrous cycle in the 30 and 100 mg/kg groups, and increased serum T4 values were observed in the 100 mg/kg groups of both sexes. In addition, we also noted other findings, such as reduced body weight gains in the 30 and/or 100 mg/kg groups of both sexes, dilatation of the large intestinal lumen in the 100 mg/kg groups of both sexes, decreased hematopoiesis in the bone marrow and spleen, and decreased white blood cell counts in the 100 mg/kg group of male rats. Our results demonstrate that in a repeated-dose toxicity study, 4,4'-(hexafluoroisopropylidene)diphenol has various endocrine-mediated effects and its NOAEL (no observed adverse effect level) is 10 mg/kg/day.
authors.affiliation: Chemicals Evaluation and Research Institute, Bunkyo-ku, Tokyo, Japan. umano-takaaki@ceri.jp
authors.forename: Takaaki
authors.initials: T
authors.lastname: Umano
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamasaki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects*; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D059551:Toxicity Tests, Subacute / Q000379:methods; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D045166:Estradiol Congeners; D010636:Phenols; C583074:bisphenol AF; D005466:Fluorocarbons; D000098826:Bisphenol A Compounds