Developmental toxicity evaluation of phthalic acid, one of the metabolites of phthalic acid esters, in rats

The objective of this study was to evaluate the developmental toxicity of phthalic acid (PA), which is one of the metabolites of phthalic acid esters (PAEs). Pregnant rats were given PA at a dose of 0 (control), 1.25, 2.5, or 5.0% in the diet on day 7 through day 16 of pregnancy. Average daily intakes of PA were 1021 mg/kg for the 1.25% group, 1763 mg/kg for the 2.5% group, and 2981 mg/kg for the 5.0% group. Maternal toxicity occurred in the 2.5 and 5.0% groups as can be seen by significant decreases in the maternal body weight gain and food consumption during the administration period. No significant changes in maternal parameters were found in the 1.25% group. Neither deaths nor clinical signs of toxicity were noted in any groups. No significant changes induced by PA were detected in the incidence of postimplantation loss and number and sex ratio of live fetuses. Significant decreases in the weight of male fetuses and number of ossification center of the caudal vertebrae were found in the 5.0% group. Morphological examinations of fetuses revealed no evidence of teratogenesis. Thus it appears unlikely that PA may be responsible for the production of the developmental toxicity of PAEs.