DEVELOPMENT OF A RAT MODEL OF TOLUENE-ABUSE EMBRYOPATHY

A rat model was developed to study toluene-abuse embryopathy, a clinic al syndrome which occurs in offspring of women who abuse toluene durin g pregnancy. On d 6-19 of gestation, eight dams received a daily gavag e 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 fet uses 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 sign ificantly 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/b ody weight ratios did not differ significantly. Morphometric analysis of brain sections demonstrated that toluene exposure resulted in small er brains together with an increase in the size of the ventricular sys tem and a reduction in the size of the caudate nucleus. Although tolue ne exposure resulted in a 13.7% reduction in maternal food consumption , the observations made in the pair-fed group did not differ from thos e made in the control group. These findings suggest that prenatal expo sure to toluene results in generalized fetal growth retardation, and t hat these effects are not due to the reduction in maternal food consum ption.