The effects of high-dose toluene on embryonic development in the rat

Developmental disability, intrauterine growth retardation, renal anomalies, and dysmorphic features have been described in offspring of women who abuse toluene during pregnancy. A Sprague-Dawley rat model was developed to study this clinical syndrome. During d 6-19 of gestation, 11 treated dams received daily gavage doses of toluene, 520 mg/kg body weight, diluted in corn oil, and 11 control dams received corn oil. This dose of toluene simulates the blood toluene levels obtained after an inhalation exposure to 3290 ppm toluene, an inhalation level in the lower end of the range experienced by toluene abusers. Maternal weight gain was 24% less in the toluene-exposed group (p < 0.002); however, there were no maternal deaths. The fetuses were delivered on d 19 of gestation, and 287 fetuses (148 toluene exposed, 139 control) were examined. Toluene treatment did not affect the number of implantations or stillbirths. There were no toluene-induced major congenital malformations or neuropathologic changes noted. In the toluene-treated group, the weights of the fetuses were reduced by 9.4% (p < 0.004) and placental weights were reduced by 10.3% (p < 0.01). Toluene exposure also reduced fetal organ weights as follows: brain 4.6%, heart 5.9%, liver 13.2% (p < 0.02), and kidney 13% (p < 0.05). Organ weight/body weight ratios did not differ significantly, suggesting that prenatal toluene exposure produced a generalized growth retardation.