Reproductive effects of nonylphenol in rats after gavage administration: atwo-generation study

The potential reproductive toxicity of nonylphenol (NP) was assessed in a t wo-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 female; were given corn oil as controls. No adverse change s in clinical signs were observed in any rats throughout the study. Signifi cant increases in the liver, kidney and pituitary gland weights in males. a nd 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 T SH 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 alteratio ns were observed in any organs including the reproductive tissues in any gr oup. Histopathologic changes were found in the liver of male and female rat s and kidneys of malts in the 50 mg/kg group. The viability of offspring fr om 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 , level for males, and decreases in LH and TSH levels and an increase in T, 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 i n 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 cha nges in any reproductive parameter, including estrous cycle, mating. fertil ity, delivery, and lactation, except for significant decreases in the numbe rs 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 ma les 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 fur ther studies. These results of NP suggested that the no observed adverse ef fect level (NOAEL) on reproductive capacity is 50 mg/kg/day or greater in p arent animals, and 10 mg/kg/day in the next generation under the present ex perimental condition. (C) 2001 Elsevier Science Inc. All rights reserved.