A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.
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.


CONCLUSIONS
These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.
Johnson
E M
EM
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000287:Administration, Topical; D000818:Animals; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000633:toxicity; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000633:toxicity*; D008727:Methotrexate / Q000633:toxicity; D011247:Pregnancy / Q000187:drug effects*; D018570:Risk Assessment; D013723:Teratogens / Q000633:toxicity; D013792:Thalidomide / Q000633:toxicity; D014212:Tretinoin / Q000008:administration & dosage / Q000633:toxicity*; D014635:Valproic Acid / Q000633:toxicity
D007641:Keratolytic Agents; D013723:Teratogens; D013792:Thalidomide; D014212:Tretinoin; D014635:Valproic Acid; D015474:Isotretinoin; D008727:Methotrexate