Retinol: Safety Considerations for its Use in Cosmetic Products

Abstract

Based on the published literature, the assessment of nonclinical and clinical data on retinol indicates absence of any systemic effects after topical or cosmetic use. Hypervitaminosis A that may be produced by the ingestion of excessive amounts of retinol or retinyl esters has never been associated with topical application. In rabbits treated with retinyl palmitate at about three times a prospective human dose level, no systemic toxicity was observed. Retinol, retinyl esters, and retinaldehyde are devoid of sensitization potential and no evidence of phototoxicity or photoallergy has been obtained. Although retinoids may be degraded to some extent by sunlight, their biological activity appears to be largely retained. In fact, topical retinoids have been shown to improve the conditions of photodamaged and photoaged skin. Topical retinol is absorbed into the epidermis and extensively metabolized, particularly by keratinocytes. Studies in human volunteers provided no evidence that topically applied retinol or retinoid metabolites are percutaneously absorbed, inducing any detectable changes in their constitutive plasma levels. In the absence of systemic exposure, topical application of the retinoids is not associated with birth defects that have been related to excessive oral intakes. Retinol and its metabolites are not only nongeno-toxic but also exert antimutagenic activity. Likewise, retinol and retinoids have antiproliferative and differentiation-inducing effects that are used effectively in the treatment of human cancer. Retinol is considered to be a safe cosmetic ingredient in the present practices of use and concentration.