Retinyl palmitate toxicity

The advantages of oil fortified with retinyl palmitate have historically been utilized by food aid programs, where a daily intake of 16 g of oil provided approximately 50 % of the recommended daily intake (RDI) of an adult male [19]. Surman et al. [20] reports that retinyl palmitate it also can be associated with toxicities at high doses. The preeise human dose required to ensure efficacy without toxicity remains a point of controversy. Also, retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity [21, 22],... 

Relatively few chronic toxicity studies with retinoids in laboratory animals have been reported. These studies have been carried out mainly in the laboratories of Hoffmann-La Roche and are unpublished except for some brief descriptive reports on retinyl palmitate (Randall, 1980), isotretinoin (Kamm, 1982), and etretinate (Teelmann, 1981). Table II presents the protocol details for chronic toxicity studies in rats and dogs with retinyl palmitate, isotretinoin, and etretinate. 

It is readily apparent from the experiments cited above that enhancement of buccal carcinogenesis by retinyl palmitate is the result of toxicity caused by excessive retinoid dosage. It is also apparent that when nontoxic doses of retinyl palmitate are used, regressive changes occur within the lesions induced by topical applications of carcinogen. The use of 13-cd-retinoic acid in experimental models for oral carcinogenesis would appear to warrant additional studies in this area using other synthetic retinoids that are now available. 

If the rate of uptake of retinol from the intestine consistently exceeds the capacity of the liver to dispose of it, significant amounts of retinol, mainly in the form of retinyl palmitate, appear in the general circulation and may give rise to toxic effects. The effects of hypervitaminosis A are many and varied. They include increased intracranial pressure, severe headache, hyperirritability, vomiting, diarrhoea, bone decalcification and skin lesions. The condition can be fatal. It has in the past been caused by over-zealous administration of concentrated sources of the vitamin such as halibut liver oil. This may contain several hundred times as much vitamin A and 40 times as much vitamin D as cod liver oil. It has also occurred in people who have eaten polar bear or husky dog liver which contain massive amounts of vitamin A. 

The parent compound in the vitamin A group is called sdl-trans retinol (Fig. lA) [4]. Its aldehyde and acid forms are retinal (Fig. IB) and retinoic acid (Fig. 1C). The active form of vitamin A in vision is ll-cis retinal (Fig. ID), and a therapeutically useful form (accutane, isotretinoin) is l3-cis retinoic acid (Fig. IE). Retinyl palmitate (Fig. IF) is a major storage form, and retinoyl p-glucuronide is a biologically active, relatively non-toxic water-soluble metabolite (Fig. IG). A synthetic aromatic analog (etretin, acitretin), shows therapeutic usefulness (Fig. IH). Finally, p-carotene, a major provitamin A carotenoid, is shown in Figure II. 

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