Assessment of the effectiveness of animal developmental toxicity testing for human safety.
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.
Daniel Baugh Institute, Department of Anatomy and Developmental Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
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D000014:Abnormalities, Drug-Induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects / Q000633:toxicity; D008253:Macaca mulatta; D008727:Methotrexate / Q000009:adverse effects / Q000633:toxicity; D051379:Mice; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013792:Thalidomide / Q000009:adverse effects / Q000633:toxicity; D014116:Toxicology / Q000379:methods*; D014635:Valproic Acid / Q000009:adverse effects / Q000633:toxicity
D013792:Thalidomide; D014635:Valproic Acid; D015474:Isotretinoin; D008727:Methotrexate