Retinyl acetate toxicity

Retinoids are needed for cellular differentiation and skin growth. Some retinoids even exert a prophylactic effect on preneoplastic and malignant skin lesions. Fenretlnide (54) is somewhat more selective and less toxic than retinyl acetate (vitamin A acetate) for this purpose. It is synthesized by reaction of all trans-retinoic acid (53), via its acid chloride, with g-aminophe-nol to give ester 54 (13). 

Moore and Wang (1945), using pure crystalline retinyl acetate, established that the skeletal changes were indeed a direct result of excessive ingestion of nonlethal, toxic doses of the vitamin. These workers fed 8.5-13.6 mg retinol... 

Many retinamides are less toxic than the corresponding free carboxylic acids or retinyl esters. Thus, the studies of Moon et al. (1979) and Hixson and Denine (1979) showed the relatively low toxicity of 4-hydroxyphenylretinamide and ethylretinamide, compared either to retinoic acid or retinyl acetate. 

Acute reactions have also been seen in patients treated for dermatologic conditions. Frey and Schock (1952) reported that psoriatic adults given high oral doses of retinyl acetate experienced symptoms of acute toxicity. While doses of 136 mg retinol equivalents (as retinyl acetate) were well tolerated, doses of 340 mg resulted in dryness, scaling, and lip fissuring, and doses of 680-1360 mg resulted in redness, scaling, nausea, and dizziness. 

Hixson EJ, Denine EP (1979) Comparative subacute toxicity of retinyl acetate and three synthetic retinamides in Swiss mice. J Nat Cancer Inst 63 1359-1364... 

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