Comparative developmental toxicity evaluation of di-n-hexyl phthalate and dicyclohexyl phthalate in rats

To investigate the effects of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) on the development of fetus and placenta in utero, pregnant rats were exposed to DHP or DCHP at dosages of 0, 20, 100, and 500 mg/kg bw/day, by gavage, on gestational days 6–19. Anogenital distance (AGD) and AGD–body weight 1/3 ratio of female fetuses decreased in all treatment groups in a non-dose–response way. The ossification centers of bones and the intensity of Alizarin red stain of the fetuses decreased in all treatment groups. The white blood cell levels of fetuses in DHP and DCHP exposed groups increased at all dosages. Mean cell hemoglobin, hemoglobin concentrations, and hemoglobin levels of all DHP and DCHP treated male and female fetuses were reduced. Histopathologic changes (hemorrhage in labyrinth, degeneration of spongiotrophoblast, hemorrhage, decreased and irregular vessel formation, and edema in the basal zone) were observed in placentas at high dosages of DHP and DCHP. In contrast, there was no change in weight gain of dams in DHP and DCHP exposed groups compared to control, but resorption rate, reduced fetal weight, delayed ossification, placental disruption, and hematologic parameters clearly indicated that in utero DHP and DCHP exposure resulted in intrauterine growth retardation in rats.