- Full (HTML) - Related EHP Articles - Purchase This Issue

Robert N. Wine,¹ Ling-Hong Li,¹ Leta Hommel Barnes,² Dushyant K. Gulati,² and Robert E. Chapin¹

¹National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 USA; ²Environmental Health Research and Testing, Lexington, KY 40503 USA

Abstract

The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics ; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F₀ rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by <13%. In tests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F₀ females had a 14% reduction in body weight, and both sexes had by 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F₁ mating trial, indices of mating, pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered out of 20 cohabited pairs) , concomitant with a 13% decrease in dam body weight. Live F₂ pup weights were 6-8% lower in all dose groups. F₁ necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F₁ males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development ; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation. Key words: continuous breeding, developmental defects, di-n-butylphthalate, rat, reproductive toxicity. Environ Health Perspect 105:102-107 (1997)

Address correspondence to R.E. Chapin, National Institute of Environmental Health Sciences, P.O. Box 12233, Mail Drop A2-02, Research Triangle Park, NC 27709 USA.

This work was conducted under contract NO1-ES-65142 to the National Institute of Environmental Health Sciences. The authors are indebted to Brad Collins and Tom Goehl for assistance in procuring and characterizing the DBP, to Jerry Heindel for support and encouragement, and to Paul Foster and Kim Treinen for stimulating discussions. The statistical support was provided by Analytical Sciences Inc., Durham, NC, and chemistry support was provided by Midwest Research Institute and Research Triangle Institute under contracts NO1-ES-45060 and NO1-ES-45061, respectively.

Received 20 August 1996 ; accepted 18 September 1996.