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 Swiss albino (CD-l) mice (n=28-30 per group, except n=14 at 2.0% BBP). BBP (0, 0.1, 0.5, 1.25 or 2.0% in feed) was administered between the mornings of gestational day (gd) 6 and 15. At sacrifice (gd 17), 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 0.1% BBP (0.182 g/kg/day). At 0.5% BBP (0.910 g/kg/day), maternal effects were limited to a 15% reduction in wt. gain during treatment. The percent nonlive implants/litter (i.e., resorptions plus late fetal deaths) was increased at 0.5% BBP (15% vs. 8% for controls), as was the percent fetuses malformed/litter (14% vs. 4%). Dams in the 1.25% BBP (2.330 g/kg/day) group showed a 71% reduction in gestational wt. gain, a 66% reduction in treatment wt. gain, and a 25% reduction in corrected wt. gain. Absolute liver wt. was decreased, and relative liver and kidney wts. were increased in the absence of treatment-related microscopic lesions. Relative food intake (g/kg/day) was increased by 27% (gd 15 to 17) and relative water intake by 35-36% (gd 12 to 17). Also at 1.25% BBP, the percent nonlive implants/litter was increased (93% vs. 8%), average fetal body wt./litter was reduced by 17%, and the percent malformed fetuses/litter was increased (89% vs. 4%). The 2.0% BBP dose (4.121 g/kg/day) was eliminated after evaluation of 14 dams since all implanted conceptuses were resorbed. In summary, 0.1% dietary BBP was a no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity. At 0.5%, BBP produced minimal evidence of maternal toxicity (reduced wt. gain during treatment) and significant developmental toxicity (increased prenatal mortality and malformations). At 1.25% BBP and 2.0%, significant maternal and embryo/fetal effects were observed, including greater than 90% prenatal mortality.