The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Butyl benzyl phthalate, a phthalate ester plasticizer, was evaluated for maternal and developmental toxicity in timed-pregnant Sprague-Dawley derived (CD) rats (27-30/group). BBP (0, 0.5, 1.25 or 2.0%) in feed between the mornings of gestational day 6 and 15 yielded average doses of 0, 0.42, 1.10 or 1.64 g BBP/kg/day, respectively. At sacrifice (gd 20), the status of implantation sites was recorded; each fetus was weighed and examined for external, visceral and skeletal malformations. No maternal or embryo/fetal effects were observed at 0.5% BBP other than increased relative water intake (g/kg/day) between gd 15 and 18. Dams in the 1.25% BBP group exhibited a 37% reduction in weight gain during treatment, increased relative liver wt., increased relative food intake (11-25% after gd 12), and increased relative water intake (18-41% after gd 9). At 1.25% BBP, the percent fetuses with variations/litter was increased, and the percent fetuses malformed/litter (5.9% vs. 2% for controls) approached statistical significance. Dams in the 2% BBP group showed a 93% reduction in treatment weight gain, and a 17% reduction in corrected weight gain. Relative liver and kidney weights were increased. Relative food intake was initially decreased (14% for gd 6 to 9), and later increased (16-44% after gd 12). Relative water intake was increased (25-73% after gd 9). At 2% BBP, the resorptions/litter were increased (40% vs. 4% for controls), average fetal body weight/litter was reduced by 20%, and the percent malformed fetuses/litter was increased (53% vs. 2% for controls).
In summary, 0.5% dietary BBP was a no-observed-adverse-effect level for both maternal and developmental toxicity. The mid-dose (1.25% BBP) produced significant maternal toxicity and minimal evidence of developmental toxicity. At the high dose (2% BBP), significant maternal and developmental toxicity was observed, including an increased incidence of malformations.