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Abstract for RACB89012

Reproductive Toxicity of Di-N-Butyl Phthalate in Sprague-Dawley Rats

CASRN: 84-74-2
Chemical Formula: C16H22O4
Molecular Weight: 278.348
Report Date: September 1991


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Di(n-butyl)phthalate (DBP) is used as a plasticizing agent in polyvinyl chloride products. DBP in feed was tested for its effects on fertility and reproduction in CD Sprague-Dawley rats according to the Continuous Breeding Protocol. Based on results of a dose-finding study and the information available in the literature, 0.1, 0.5, and 1.0% were chosen to investigate effect on fertility and reproduction. This yielded average doses of approximately 66, 320 and 651 mg DBP/kg/day.

Male and female rats (F0) were continuously exposed for a 7-day precohabitation and a 112-day cohabitation period (Task 2). Treated male and female body weights in Task 2 were within 10% of control body weights. Feed consumption values for 1.0% treated females were 18 and 8% lower compared to the control value for week one and six respectively, and body weights of the F0 dams were decreased at all time points. Reproductive endpoints adversely affected by DBP in the F0 generation were the total number of live pups per litter (all groups) and live pup weights (middle and high dose groups). In Task 3, designed to determine the affected sex, the weights of pups from treated females were significantly decreased. At necropsy, F0 females showed decreased body weights and increased kidney- and liver- to-body weight ratios compared to controls. F0 males had increased absolute liver weights and increased liver-, kidney-, right cauda-, and epididymis-to-body weight ratios. Sperm parameters were not affected.

The F1 pups from the final litter in the control and all three groups were weaned for second generation studies. Mating, pregnancy and fertility indices for F1 rats in the 1.0% dose group were all significantly decreased in the presence of a significant decrease in F1 female dam body weights. Live F2 pup weights were significantly lower in all treated groups.

At F1 female necropsy, body and organ weights were significantly lower in the 1.0% group For F1 males, body weight and all reproductive organ-to-body weight ratios were lower while kidney and liver ratios were higher. Epididymal sperm count and testicular spermatid head count were significantly decreased in the 1.0% treated group. In the 1.0% group, histopathologic evaluation showed degenerated seminiferous tubules in the testis in 8 of 10 animals and underdeveloped epididymis in 5 of 19 animals examined.

The present study showed that DBP is a reproductive toxicant in the presence of systemic toxicity in Sprague-Dawley rats exposed both as adults and during development. Overall, the data indicate that effects on the second generation were greater than on the first generation.

NTIS # PB92111996