Reproductive effects of nonylphenol in rats after gavage administration: a two-generation study.
The potential reproductive toxicity of nonylphenol (NP) was assessed in a two-generation reproductive toxicity study. Groups of 25 male and female Crj:CD (SD) IGS rats were given NP by gavage at levels of 2, 10, or 50 mg/kg, and 25 males and females were given corn oil as controls. No adverse changes in clinical signs were observed in any rats throughout the study. Significant increases in the liver, kidney and pituitary gland weights in males, and decreases in thymus weight in males and in ovary weight in females were observed in the 50 mg/kg group. NP did not affect sperm characteristics or the estrous cycle at any dose administered. A significant increase in the TSH level was observed in males in the 50 mg/kg group. No adverse effects of NP on reproduction were found. At necropsy, no treatment-related alterations were observed in any organs including the reproductive tissues in any group. Histopathologic changes were found in the liver of male and female rats and kidneys of males in the 50 mg/kg group. The viability of offspring from postnatal day 0 to 4 in the 50 mg/kg group was reduced as compared with that in the controls, although growth was not affected by NP administration. On postnatal day 22, an increase in the serum FSH level and decrease in T(3) level for males, and decreases in LH and TSH levels and an increase in T(3) levels for females were observed in the 50 mg/kg group. NP did not affect the timing of preputial separation, while vaginal opening was accelerated in the 50 mg/kg group. No adverse changes were found in behavior or learning in the offspring of NP-treated groups. There were no treatment-related changes in any reproductive parameter, including estrous cycle, mating, fertility, delivery, and lactation, except for significant decreases in the numbers of implantation sites and live pups, and a significant decrease in ovary weight in the 50 mg/kg group. Kidney and liver weight were increased in males in the 50 mg/kg group. Histopathologic examination revealed changes in the liver of males and females of the 50 mg/kg group. No treatment-related changes were observed in the sperm characteristics. Hormone data should be interpreted cautiously until the findings are repeated and confirmed by further studies. These results of NP suggested that the no observed adverse effect level (NOAEL) on reproductive capacity is 50 mg/kg/day or greater in parent animals, and 10 mg/kg/day in the next generation under the present experimental condition.
Nagao
T
T
Department of Reproductive and Developmental Biology, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, 257-8523, Hadano, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp
Wada
K
K
Marumo
H
H
Yoshimura
S
S
Ono
H
H
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007774:Lactation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D010908:Pituitary Hormones, Anterior / Q000097:blood; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D018675:Toxicity Tests; D014284:Triiodothyronine / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D004785:Environmental Pollutants; D010636:Phenols; D010908:Pituitary Hormones, Anterior; D014284:Triiodothyronine; C025256:nonylphenol