Evaluations of studies for four well-known human developmental toxicants clearly suggest that a margin of exposure of 1/100th the NOAEL for the most sensitive animal species tested provides adequate safety for the human conceptus. The lowest reported human teratogenic exposures occurred at doses at least one log above the estimated "safe" or acceptable daily exposure based on the most sensitive animal species, that is, 1/100th animal NOAEL. (The MOE ranged from < 1 to 10.). The data and analyses are consistent with the conclusion that, regardless of the type of in utero effect produced in animals, the margin of safety of 100 is likely to protect the human conceptus in utero from developmental perturbation, and it is a scientifically reasonable and conservative default number.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

1,1,3,3-tetrachloroacetone: teratogenicity study in mice and rabbits.

The teratogenicity of tetrachloroacetone (TCA) was evaluated in CF-1 mice and New Zealand white rabbits. Mice were given 0, 5, 15 or 50 mg/kg/day of TCA by gavage on days 6 through 15 of gestation. Rabbits were given 0, 1, 5, or 10 mg/kg/day on days 6 through 18 of gestation. The incidence of malformed fetuses was not significantly increased among mice given 5, 15 or 50 mg/kg/day of TCA. Sixteen fetuses in 3 litters in the 50 mg/kg/day group had cleft palate; they were from three dams which showed the most severe signs of toxicity, including depressed weight gain, decreased water consumption, and gastric ulceration. Dosage with 5 mg/kg/day, a level which was not toxic to the pregnant female, was not toxic to developing mouse fetuses. Fetal effects in rabbits were limited to a slight, but not statistically significant or dose related increase in the incidence of malformed fetuses. On the basis of these results, TCA does not appear to represent a unique hazard to the conceptus.

Acetone↗