Toluene is a commonly abused organic
solvent. Inhalant abusers are increasingly women in their prime childbearing years. Children born to mothers who abused
solvents during pregnancy may exhibit characteristics of a "fetal
solvent syndrome" which may include dysmorphic features. This study examined the teratological effects of an abuse pattern of binge
toluene exposure during gestation on skeletal and soft tissue abnormalities,
body weight, and body size in fetal rats. Pregnant Sprague-Dawley rats were exposed for 30 min, twice daily, from gestational day (GD) 8 through GD20 to either air (0 ppm), 8000 ppm, 12,000 ppm, or 16,000 ppm
toluene. Two-thirds of each litter was prepared for skeletal examination using
Alizarin Red S staining while the remaining third of each litter was fixed in
Bouin's solution for Wilson's soft tissue evaluation. Exposure to
toluene at all levels significantly reduced growth, including decreases in placental
weight, fetal weight, and crown-rump length. In addition, numerous gross morphological anomalies were observed such as short or missing digits and missing limbs. Skeletal examination revealed that ossification of the extremities was significantly reduced as a result of
toluene exposure at all levels. Specific skeletal defects included misshapen scapula, missing and supernumerary vertebrae and ribs, and fused digits. Soft tissue anomalies were also observed at all
toluene levels and there was a dose-dependent increase in the number of anomalies which included
cryptorchidism, displaced abdominal organs, gastromegaly, distended/hypoplastic bladder, and delayed cardiac development, among others. These results indicate that animals exposed prenatally to levels and patterns of
toluene typical of
inhalant abuse are at increased risk for skeletal and soft tissue abnormalities.