Reproductive effects in male and female rats from neonatal exposure to p-octylphenol.
A number of alkylphenolic compounds are used in a variety of commercial products and have been shown in in vitro studies to be weakly estrogenic, but in vivo data are not available addressing this issue in mammals. Human exposure to alkylphenols may occur not only from these environmental contaminants but also through contact with manufactured and metabolic breakdown products. In this study, Sprague-Dawley rats were exposed to octylphenol by oral gavage at doses of 0 (vehicle: corn oil), 12.5, 25, 50, or 100 mg/kg once daily on postnatal days 1 through 5 to examine its effects on male and female reproductive function after puberty. In addition, preputial separation and vaginal opening as endpoints of sexual maturation, estrous cycling, sperm count, serum testosterone concentration, and histopathologic changes of the reproductive organs of male and female rats were examined. Male reproductive organs were weighed at necropsy. Body weights of male and female rats exposed to octylphenol at 50 and 100 mg/kg throughout the study after the administration period, those of both sexes at 7 and 9 weeks of age in the 25 mg/kg group, and that of females at 9 weeks of age in the 12.5 mg/kg group were lower than those of controls. Significant delays in acquisition of puberty in males and females exposed to octylphenol at 50 and 100 mg/kg were observed. Estrous cycle, copulation and fertility, sperm count, and serum testosterone concentration were not affected by neonatal exposure to octylphenol. Significant decrease in absolute and relative prostate weight in the 12.5, 25, 50, and 100 mg/kg groups, and absolute epididymal weight in the 100 mg/kg group, increase in relative testes weight in the 100 mg/kg group, and relative seminal vesicle weights in the 50 and 100 mg/kg groups were found. Histopathologic analyses of reproductive organs in male and female rats exposed neonatally to octylphenol revealed no marked alterations. The results of this study indicate that early neonatal exposure to octylphenol by oral gavage did not cause dysfunction of reproductive performance (mating and fertility) in male or female rats, and no disruption of development of the reproductive tract was observed in male or female rats, while significant decreases in body weights in the 25 mg/kg and more groups, delays of sexual maturation in the 50 mg/kg and greater groups, and decrease in ventral prostate weights in all octylphenol-treated groups were found. Therefore, it is concluded that NOAEL (no-observed adverse effect level) for systemic toxicity was < or =12.5 mg/kg/day and that for reproductive toxicity was 100 mg/kg/day under the present experimental condition.
Nagao
T
T
Department of Reproductive and Developmental Biology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp
Yoshimura
S
S
Saito
Y
Y
Nakagomi
M
M
Usumi
K
K
Ono
H
H
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; 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; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects
D004968:Estrogens, Non-Steroidal; D010636:Phenols; C080417:4-octylphenol