Systemic and Developmental Toxicity of Dermally Applied Distillate Aromatic Extract in Rats

Distillate aromatic extract (DAE) was evaluated for subchronic and developmental toxicity. In the subchronic study, undiluted DAE was applied on the shaved backs of male and female rats at dose levels of 0, 30, 125, 500, and 1250 mg/kg for 13 weeks, 5 days per week. Exposure sites were not covered. In the developmental toxicity study, DAE was similarly applied, but to pregnant rats at dose levels of 0, 8, 30, and 125 mg/kg on Gestation Days 0–19, 500 mg/kg on Gestation Days 0–16, and 1000 mg/kg on Gestation Days 10–12. Evidence of toxicity observed in the subchronic study included death, decreased body weights, aberrant serum chemistry and hematology values, altered organ weights, and histopathologic changes in a variety of organs. Regardless of the length of the exposure period, DAE was toxic to the developing conceptus. Evidence of developmental toxicity observed included increased resorptions and reduced fetal body weights. Cleft palate and ossification delays were observed in fetuses exposed in utero to DAE on Gestation Days 10–12, but not when exposure spanned all (Gestation Days 0–19) or most (Gestation Days 0–16) of gestation.