Diethyl phthalate, a member of the phthalic acid ester class of plasticizers, was evaluated for toxic and teratogenic effects in timed-pregnant CD rats (n=27-32 confirmed pregnancies/group). Dietary concentrations of 0, 0.25, 2.5, and 5.0% DEP were administered on gestational days 6 through 15, with resulting average doses of 198, 1909 and 3214 mg/kg/day for the low-, mid- and high-concentration groups, respectively.
Females were weighed and observed daily during treatment for clinical signs. Maternal food and water consumption was measured throughout gestation. At sacrifice on gd 20, maternal liver and kidneys were weighed. In addition, the uterus of each dam was weighed, and the number and status of uterine implantation sites were recorded. Each live fetus was weighed, sexed, and examined for external, visceral, and skeletal malformations.
No adverse effects upon maternal status were observed at 0.25% DEP in the diet; this group exhibited increased body weight (gd 20), weight gain (gd 6-15 and gd 0-20), and corrected weight gain relative to controls. Transient maternal toxicity in the form of reduced body weight after three days of exposure (gd 9) was observed in the 2.5% dose group with recovery by gd 12. Reduction in maternal body weight gain was observed in the 5. O% dose group during the treatment period (gd 6-15), and in body weight on gd 9, 12, 15, and 18. Maternal food and water consumption (both absolute and relative) were depressed between gd 6-9 (after initiation of dosing on gd 6) in the 2.5% DEP and 5.0% DEP groups. Depression of food intake at 5.0% DEP continued during gd 9-12. A rebound increase in relative food consumption (g/kg/d) was noted between gd 12-15 at 2.5% DEP and between gd 12-15, 15-18, and 18-20 at 5.0% DEP.
No adverse effects upon embryo/fetal growth, viability or the incidence of malformations were observed even at 5 0% DEP in the feed The incidence of extra rib, classified as a variation in this species and strain, was significantly increased at 5 .0% DEP in the feed.
In conclusion, DEP administered to pregnant CD rats during the period of major organogenesis had no adverse effect upon embryo/fetal development except for an increased incidence in extra rib (an anatomical variation) at a maternally toxic exposure level.