Reproductive effects in male and female rats from neonatal exposure to p-octylphenol. 2001

T Nagao, and S Yoshimura, and Y Saito, and M Nakagomi, and K Usumi, and H Ono
Department of Reproductive and Developmental Biology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp

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.

UI MeSH Term Description Entries
D008297 Male Males
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D012098 Reproduction The total process by which organisms produce offspring. (Stedman, 25th ed) Human Reproductive Index,Human Reproductive Indexes,Reproductive Period,Human Reproductive Indices,Index, Human Reproductive,Indexes, Human Reproductive,Indices, Human Reproductive,Period, Reproductive,Periods, Reproductive,Reproductive Index, Human,Reproductive Indices, Human,Reproductive Periods
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004968 Estrogens, Non-Steroidal Non-steroidal compounds with estrogenic activity. Estrogens, Nonsteroidal,Estrogens, Non Steroidal,Non-Steroidal Estrogens,Nonsteroidal Estrogens
D005260 Female Females
D005835 Genitalia The external and internal organs involved in the functions of REPRODUCTION. Accessory Sex Organs,Genital Organs,Sex Organs, Accessory,Genital System,Genitals,Reproductive Organs,Reproductive System,Accessory Sex Organ,Genital,Genital Organ,Genital Systems,Organ, Accessory Sex,Organ, Genital,Organ, Reproductive,Organs, Accessory Sex,Organs, Genital,Organs, Reproductive,Reproductive Organ,Reproductive Systems,Sex Organ, Accessory,System, Genital,System, Reproductive,Systems, Genital,Systems, Reproductive
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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