Development of a rat model of toluene-abuse embryopathy

A rat model was developed to study toluene-abuse embryopathy, a clinical syndrome which occurs in offspring of women who abuse toluene during pregnancy. On d 6-19 of gestation, eight dams received a daily gavage dose of toluene, 650 mg/kg body weight, diluted in corn oil, whereas eight control dams and eight pair-fed dams received corn oil. The fetuses were delivered on d 19 of gestation. In the toluene-exposed group, the weights of the fetuses were reduced by 21.6% (p < 0.001), and a delay in skeletal ossification was demonstrated. Toluene exposure significantly reduced the weight of the fetal brain by 11.9% (p < 0.001), as well as the weights of the heart, liver, and kidney. Organ weight/body weight ratios did not differ significantly. Morphometric analysis of brain sections demonstrated that toluene exposure resulted in smaller brains together with an increase in the size of the ventricular system and a reduction in the size of the caudate nucleus. Although toluene exposure resulted in a 13.7% reduction in maternal food consumption, the observations made in the pair-fed group did not differ from those made in the control group. These findings suggest that prenatal exposure to toluene results in generalized fetal growth retardation, and that these effects are not due to the reduction in maternal food consumption.