Localized skin changes induced by depot injections of vitamin A in the rat

Consistent local dermal hypervitaminotic A effects without systemic toxicity were produced in male albino rats injected intramuscularly with high doses of vitamin A palmitate. There was a loss of hair overlying the site of injection, accumulation of UV-fluorescent fat droplets in dermal and hypodermal macrophages and in the stratum Malpighi, intercellular epidermal edema, thickening of the stratum Malpighi and thinning of the stratum corneum. Subcutaneous administration of the same dose of vitamin A palmitate or intramuscular injection of vitamin A alcohol did not produce any skin lesions although morphologic examination of liver specimens from all the vitamin-treated animals revealed storage of vitamin A. Accumulation of the vitamin in macrophages in the dermis was always seen in specimens of skin overlying the site of intramuscular injection of vitamn A palmitate, suggesting that the changes in epidermis may be due to sustained release from this local intracellular store. Application of this method of parenteral administration of the esterified form of the agent will facilitate its use in studies of promotion or inhibition of tumorigenesis and in disorders of keratinization.