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.
Dimethyl phthalate, a member of the phthalic acid ester class of plasticizers, was evaluated for developmental toxicity in timed-pregnant Sprague-Dawley (CD) rats. On gestational days (gd) 6 through 15, dietary concentrations of 0. 0.25. 1.0 and 5% DMP were administered resulting in an estimated average DMP intake of 0. 0.2, 0.8 and 3.6 g/kg/day. Females (25-28 confirmed pregnancies/group) were observed daily during and after treatment for clinical signs. Maternal body weight and food and water consumption were measured throughout gestation. At necropsy (gd 20), maternal body, liver, kidney and gravid uterus were weighed. The number and status of uterine implantation sites were recorded. Each live fetus was weighed, sexed, and examined for external, visceral and skeletal malformations.
High-dose DMP resulted in transient reductions in food and water consumption and body weight during early treatment. When treatment ended, food and water consumption rose above controls. Animals fed 5% DMP also exhibited reduced body weight gain during the treatment period and increased relative liver weight. Neither 0.25% nor 1.0% DMP treatment had significant maternal effects, with the exception of reduced water consumption during early treatment and increased food and water consumption following treatment (1.0% only). These results suggest that the apparent toxic effects of high-dose DMP on body weight may reflect the unpalatability of DMP in feed. The no-observed-adverse- effect level for maternal toxicity was 1.0% DMP.
There was no effect of treatment on embryo/fetal viability, average litter size, fetal body weight, or the incidence of external, skeletal or visceral malformations, even at doses producing significant maternal effects. Therefore, the NOAEL for developmental toxicity was 5.0% DMP.
In summary, in this study in CD rats, maternal toxicity was observed at a dietary treatment level of 5.0% DMP. No developmental endpoints were affected under the conditions of this study.