National Toxicology Program

Developmental Toxicity of Dimethyl phthalate (CAS No. 131-11-3) Administered to CD Rats on Gestational Days 6 Through 15

NTP Study: TER88066

ABSTRACT

Dimethyl phthalate (DMP), 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 (NOAEL) 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.

Report Date: January 9. 1989

NTIS# PB89164826/AS

Return to Organ Systems Toxicity Abstracts