The objective of this study was to evaluate the developmental toxic potential of di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague-Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg -1 per day, by gavage, on gestational days (GD) 6-20. Maternal food consumption and body weight gain were signifi cantly reduced at 750 mg kg -1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused doserelated developmental toxic eff ects, including marked embryo mortality at 750 mg kg -1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and signifi cant decreases in fetal weight at 500 and 750 mg kg -1 per day. Signifi cant delay of ossifi cation and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg -1 per day. DCHP produced fetal growth retardation at 750 mg kg -1 per day, as evidenced by signifi cant reduction of fetal weight. DnHP and DCHP induced a signifi cant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a signifi cant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg -1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP.
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