February 2, 1998

A recent U.S. government study concluded that "NP was not a selective reproductive/ developmental toxicant." The National Institute of Environmental Health Sciences (NIEHS) study, evaluating three generations of laboratory animals ingesting varying quantities of nonylphenol, augments a recent shorter term (90-day) study sponsored by the APE Panel on nonylphenol which saw no changes in the reproductive organs of laboratory animals.

The NIEHS study was designed to "assess reproductive effects over multiple generations" and to "define a no effect level for reproductive and developmental toxicity" by administering nonylphenol in the diet at concentrations of 0, 200, 650, and 2000 parts per million (ppm) to 30 male and 30 female rats over three generations. Nonylphenol has shown very weak estrogenic characteristics in various screening assays. These screening test results have raised questions about the potential of nonylphenol to disrupt the endocrine system and cause reproductive problems.

The NIEHS study found "no consistent effect on fertility" from all levels of exposure to nonylphenol. Consistent with exposure to very high doses of nonylphenol, the study found effects including "male and female reproductive changes" in rats at doses of 650 ppm and above, "based on decreased epididymal sperm density and testicular spermatid head counts in males (F2 generation only), and increased estrous cycle length and decreased ovarian weights observed in females." The study continues: "However, these changes in reproductive parameters were not linked to alterations in fertility." (Since the effects on sperm were observed in only one generation and were not associated with adverse effects, the study's author questioned whether "this represents random chance, or real biological effects.")

There were no adverse reproductive effects at doses of 200 ppm, which translates to a "No Observable Effect Level" (NOEL) for reproductive toxicity of 15 milligrams of nonylphenol per kilogram of body weight in rats. This NOEL for rats is several multiples of 10 higher than an estimated, maximal daily human intake. In addition, there were no adverse effects on fertility at doses of 2000 ppm, which means the "No Observable Adverse Effects Level" (NOAEL) is greater than 150 milligrams of nonylphenol per kilogram of body weight in rats.

The study notes that a "maximum tolerated dose was reached for the 2000 ppm animals, based on decreased body weight gain and the presence of renal lesions." In addition, the study concluded that nonylphenol is not a reproductive or developmental toxicant, "since reproductive changes were seen only concomitant with body weight and organ weight changes."

The findings in the NIEHS study were similar to a recent 90-day feeding study sponsored by the APE Panel which evaluated the subchronic toxicity of nonylphenol in laboratory rats. However, in the 90-day study, at dietary doses of up to 2000 ppm, no changes were noted in reproductive organs, in the estrus cycle of female rats or in sperm counts of male rats.

The NIEHS report is available through the National Technical Information Service (703.605.6000) or on the World Wide Web at http://ntp-server.niehs.nih.gov/htdocs/RT-studies/RACB94021.html. For further information on either of the studies, please contact the APE Panel at the number below.