title: A repeated 28-day oral dose toxicity study of nonylphenol in rats, based on the 'Enhanced OECD Test Guideline 407' for screening of endocrine-disrupting chemicals.
abstract: A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the 'Enhanced OECD Test Guideline 407' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Gye-Hyeong
authors.initials: GH
authors.lastname: Woo
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ichiki
authors.forename: Masao
authors.initials: M
authors.lastname: Hamamura
authors.forename: Kyoung-Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049108:Cell Enlargement / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D004435:Eating; D052244:Endocrine Disruptors / Q000145:classification / Q000633:toxicity*; D004702:Endocrine Glands / Q000187:drug effects* / Q000473:pathology; D004700:Endocrine System Diseases / Q000139:chemically induced* / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D018737:Hand Strength; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D053580:Muscle Strength / Q000187:drug effects; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D014621:Vagina / Q000187:drug effects / Q000473:pathology
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D010636:Phenols; C025256:nonylphenol