Jr. Latendresse et al., Polycystic kidney disease induced in F-1 Sprague-Dawley rats fed para-nonylphenol in a soy-free, casein-containing diet, TOXICOL SCI, 62(1), 2001, pp. 140-147
para-Nonylphenol (NP; CAS #84852-15-3); an alkylphenol with a 9-carbon olef
in side chain, is widely used in the manufacture of nonionic surfactants, l
ubricant additives, polymer stabilizers, and antioxidants, Due to its wide
commercial use and putative endocrine activity in humans and wildlife, the
NTP elected to assess its effects on reproduction in multigenerational stud
ies. To avoid known estrogenic activity of phytoestrogens in soy and alfalf
a, a soy- and alfalfa-free, casein-containing diet was used in a range-find
ing study to determine the doses of NP to be tested further. NP was adminis
tered to Sprague-Dawley rats in the diet at 0, 5, 25, 200, 500, 1000, or 20
00 ppm to F-0 dams beginning on gestation-day 7, The F-1 pups were weaned a
t postnatal day (PND) 21, and their exposure via diet was continued at the
same dose level as their respective dams. Pup weights from birth through we
aning were not significantly different from controls in any dose group, but
the average weight of both sexes was significantly less compared to contro
ls, beginning with the PND 28 weighing. The F-1 rats were sacrificed on PND
50 (n = 15, 3 pups of each sex from 5 litters for all dose groups). Termin
al body weights of males and females in the 2000-ppm dose group were 74% an
d 85% of controls, respectively. Severe polycystic kidney disease (PKD) was
present in 100% of the 2000 ppm-exposed male and female rats. At 1000 ppm,
67% of males and 53% of females had mild to moderate PKD versus none of ei
ther sex in the control and lower-dose groups. The no-adverse-effect level
(NOAEL) for PKD was determined to be 500 ppm. Previous studies with compara
ble duration and route of exposure, but using soy-containing diets, reporte
d either no or only mild PKD at 2000 ppm NP. We conclude that the renal tox
icity of NP is highly dependent on the diet on which the animals are mainta
ined, The potential interaction of diet and test compounds on nonreproducti
ve as well as reproductive endpoints should be considered when contemplatin
g the use of special diets formulated to minimize exogenous "hormone" conte
nt for the study of the effects of putative endocrine disruptive chemicals.