SUBCHRONIC TOXICITY (90-DAY) STUDY WITH PARA-NONYLPHENOL IN RATS

As a component to the risk assessment process for para-nonylphenol (NP ; CASRN 84852-15-3), a 90-day study was conducted in rats following U. S. EPA TSCA guidelines and Good Laboratory Practice regulations. NP wa s administered to four groups of rats at dietary concentrations of 0, 200, 650, or 2000 ppm which corresponded to approximate dietary intake s of 0, 15, 50, or 150 mg/kg/day, respectively. There were 25 rats/sex /group in the control and high-dose groups and 15 rats/sex/group in th e low-and middose groups. Ten of the 25 rats/sex in the control and hi gh-dose groups were designated as recovery animals and were maintained on control diets for 4 weeks after completion of the 90-day exposure period to assess the reversibility of any effects which might be obser ved. To evaluate for the possible weak estrogen-like activity that has been reported for NP in a number of screening assays, estrous cyclici ty was monitored using vaginal cytology during Week 8 of the study, an d sperm count, motility, and morphology were evaluated at termination. In-life effects from NP exposure were limited to small decreases in b ody weight and food consumption in the 2000-ppm dose group. Postmortem measurements at Week 14 indicated a dose-related kidney weight increa se in males and a decrease in renal hyaline globules/droplets in males from the high-dose group. The kidney weights showed complete recovery following the 4-week postdosing recovery period. Due to the small mag nitude of the changes (i.e., all weights were within or near laborator y historical control values) and the lack of correlating clinical or h istopathological changes, the kidney weight alterations were not consi dered toxicologically significant. The biological significance of redu ced hyaline in the kidneys of male rats from the high-dose group is un certain. Renal tubular hyaline is associated with the rat-specific pro tein, cy-au-globulin, and, therefore, this finding was not considered toxicologically relevant to humans. No other effects attributable to N P were observed. No changes were observed for estrous cycling, sperm e valuations, or effects on endocrine organs, NP, therefore, did not man ifest any estrogen-like activity as measured in these parameters at di etary concentrations as high as 2000 ppm, the maximum dose administere d in this study. Based on the minor findings for the 2000-ppm dose gro up, the NOAEL (no-observed-adverse-effect level) for NP in this study is considered to be 650 ppm in the diet, corresponding to an approxima te intake of 50 mg/kg/day. (C) 1997 Academic Press.