BACKGROUND: Although topically applied all-trans-retinoic acid (tretinoin) 
undergoes minimal absorption and adds negligibly to normal endogenous levels, 
its safety in humans is occasionally questioned because oral ingestion of 
retinoids at therapeutic levels is known to entail teratogenic risks.
OBJECTIVE: To assess the actual potential for developmental toxicity from 
treatment with topical tretinoin.
METHODS: Risk assessments were conducted on four known human developmental 
toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a 
potential developmental toxicant (acetylsalicylic acid). The margin of safety 
for each chemical was calculated from the ratio of animal no-observed adverse 
effect levels to human lowest-observed adverse effect levels or estimated 
exposure doses.
RESULTS: The derived safety margin of more than 100 for topical tretinoin (with 
2% absorption) contrasted sharply with the near unity values for valproic acid, 
methotrexate, thalidomide, and isotretinoin and was larger than that for 
acetylsalicylic acid.
CONCLUSION: These data support other epidemiologic and animal data that topical 
tretinoin is not a potential human developmental toxicant.