Effects of prenatal and postnatal exposure to styrene dimers and trimers on reproductive function in rats.
Styrene dimers and trimers (SDT) were evaluated for reproductive toxicity in Sprague-Dawley rats. SDT was administered orally to rats at doses of 0, 0.04, 0.2, and 1.0 mg/kg from day 6 of gestation through day 21 after delivery. Clinical signs, including pregnancy and lactation, and changes in body weight and food consumption were assessed. All dams underwent a gross necropsy examination. The brain, liver, kidney, ovary, uterus, thyroid gland, and pituitary were weighed. Offspring were evaluated for the effects of the test compound on viability, growth, anogenital distance, preputial separation and vaginal opening, behavioral function, estrous cycling, mating, and fertility. There were no test compound-related clinical signs or effects on body weight or food consumption in dams during any phase of the study. In addition, no abnormalities in delivery or lactation, including gestation length, were noted in any dam. No dose-dependent changes were observed in pup viability or growth. There were no adverse effects of SDT on any developmental landmark, learning, memory, or estrous cycling in offspring. The number of days to inseminations in the 0.2 mg/kg group was significantly greater than that in the control group, but was independent of dose. No test compound-related necropsy findings were seen in either the dams or the offspring. No compound-related histopathologic findings were noted in the reproductive tissues of either the male or female offspring. No compound-related alterations in sperm motion or density were detected in the offspring. Thyroid stimulating hormone levels in the male offspring of the 0.2 mg/kg and 1.0 mg/kg groups were significantly higher than those in the controls, whereas thyroid hormone (T(3), T(4)) levels in these groups were comparable to the controls. In addition, the thyroid glands of males in all groups were similar histologically. These results indicate that SDT administered at doses as high as 1.0 mg/kg (1000 times the estimated human daily intake) did not produce reproductive toxicity in dams or offspring.
Nagao
T
T
Department of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp
Wada
K
K
Kuwagata
M
M
Ono
H
H
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004971:Estrus / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000097:blood; D007774:Lactation / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D012741:Sexual Maturation / Q000187:drug effects; D013076:Sperm Count; D020058:Styrene / Q000633:toxicity*
D006728:Hormones; D020058:Styrene