Comparative toxicity study of 3-aminophenol in newborn and young rats.
Repeated dose toxicity of 3-aminophenol was examined on oral administration to newborn and young rats, and susceptibility was analyzed in terms of the no observed adverse effect level (NOAEL) and the unequivocally toxic level. In the 18-day newborn rat study, starting at day 4 after birth, tremors and depression of body weight gain were observed, as well as hypertrophy of thyroid follicular epithelial cells and increases of relative liver and kidney weights at 240 mg/kg. Increase of relative liver weights in males and decrease of blood sugar in females without any histopathological changes at 80 mg/kg were not considered to be adverse effects. No chemical-related changes were observed at 24 mg/kg. Abnormalities of external development and reflex ontogeny in the newborn were not observed. In the 28-day study, starting at 5 weeks of age, depression of body weight gain, tremors, anemia, and liver, kidney and thyroid toxicity were observed at 720 mg/kg. Although slight pigmentation in the renal proximal tubular epithelium was observed in females at 240 mg/kg, this was not considered to be an adverse effect because of the lack of changes in related toxicological parameters. It was concluded that the NOAEL is 80 mg/kg/day in newborn rats and 240 mg/kg/day in young rats, with unequivocally toxic levels of 240 mg/kg/day and 720 mg/kg/day, respectively. Based on these two endpoints, the susceptibility of newborn rats to the chemical was approx. 3 times higher than that of young rats, consistent with our previous results for 4-nitrophenol and 2,4-dinitrophenol.
Koizumi
Mutsuko
M
Division of Risk Assessment, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Nishimura
Nobuo
N
Enami
Tomonori
T
Sunaga
Masao
M
Horikawa
Hironao
H
Kamata
Eiichi
E
Hasegawa
Ryuichi
R
D000375:Aging / Q000502:physiology; D000627:Aminophenols / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D000627:Aminophenols; C055528:3-aminophenol