Critical period for adverse effects on development of reproductive system in male offspring of rats given di-n-butyl phthalate during late pregnancy

The objective of this study was to determine the susceptible days for the a dverse effects of di-n-butyl phthalate (DBP) on development of reproductive system in male offspring following maternal administration on successive 3 -day period during late pregnancy. Pregnant rats were given DBP by gastric intubation at 1000 or 1500 mg/kg on days 12-14 or 18-20 of pregnancy or at 500, 1000 or 1500 mg/kg on days 15-17 of pregnancy. A significant decrease in the maternal body weight gain and/or food consumption was found in the D BP-treated groups regardless of the days on which DBP at 1000 and 1500 mg/k g was given. A significant increase in the number of resorptions per litter was found in the groups given DBP at 1500 mg/kg on days 12-14 and 15-17 of pregnancy. The weights of male and female fetuses were significantly decre ased in the groups given DBP at 1000 and 1500 mg/kg on days 12-14 and 18-20 and at 1500 mg/kg on days 15-17. A significant increase in the incidence o f fetuses with undescended testes was found at 1500 mg/kg on days 12-14 and at all doses on days 15-17. A significant decrease in the anogenital dista nce (AGD) of male fetuses was observed in the groups treated with DBP regar dless of the days of treatment. The AGD/body weight ratio in male fetuses w as significantly reduced in the groups given DBP on days 15-17, but neither on days 12-14 nor 18-20. The AGD of female fetuses in the DBP-treated grou ps was comparable to that in the control group. It was concluded that perio d of days 15-17 of pregnancy was the most susceptible for DBP-induced undes cended testes and decreased AGD in male offspring. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.