Reproductive and developmental toxicity screening study of 4-aminophenol in rats.
Twelve male and female rats per group were given 4-aminophenol (PAP) by gavage at 0, 20, 100, or 500 mg/kg/day. Males were dosed for a total of 49 days, beginning 14 days before mating. Females were dosed for a total of 40-60 days, from 14 days before mating to Day 3 of lactation throughout the mating and gestation periods. Four males and 2 females died at 500 mg/kg/day, and all surviving males and females showed brown urine at 100 mg/kg/day and above. Body-weight gain was lower in males and females at 500 mg/kg/day, and food consumption was decreased in males at 500 mg/kg/day and in females at 100 and 500 mg/kg/day. Absolute and relative weights of the testes and epididymides were decreased at 500 mg/kg/day. Histopathological examinations revealed decreased spermatocyte and spermatid levels in the testis, debris of germ cell in the epididymis lumen, basophilic tubules in the kidney, and deposits of hemosiderin in the red pulp and extramedullary hematopoiesis in the spleen in males at 500 mg/kg/day. Longer gestation period, decreased delivery index, and lower body weight of pups on postnatal day (PND) 0 and increased number of stillborns at 500 mg/kg/day were also observed. At this dose, the viability of pups on PND 4 was decreased markedly. No adverse effects on reproduction or development were detected at 20 and 100 mg/kg/day. These findings indicate that PAP is general and reproductive/developmental toxic, but is unlikely to be teratogenic, in rats.
Harada
Tomoaki
T
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Kimura
Eisuke
E
Hirata-Koizumi
Mutsuko
M
Hirose
Akihiko
A
Kamata
Eiichi
E
Ema
Makoto
M
D000627:Aminophenols / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003307:Copulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D004971:Estrus / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005865:Gestational Age; D048788:Growth and Development / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000627:Aminophenols; C026729:4-aminophenol