Cancer: Retinoic acid and retinyl palmitate, in combination with sunlight, may increase skin cancer risk. In August 2012 the National Toxicology Program of the US National Institutes of Health published a report, which examined the photocarcinogenic effects of retinoic acid and retinyl palmitate. The study applied creams containing retinyl palmitate or retinoic acid to mice who were then exposed to synthetic sunlight. It found that the inclusion of these compounds in the cream increased the number of tumors and decreased the time of tumor appearance compared to animals given just the carrier cream both with and without synthetic sunlight.
It should be noted that a number of vitamin A/retinol derivatives have been suggested as cancer-preventative agents. Unlike other dietary phytochemicals proposed to be cancer-preventive due to detoxifying and antioxidant properties, retinol derivatives have been suggested as anticancer agents mainly for their effects on cellular differentiation and growth suppression. However, despite some promising laboratory and early clinical evidence for retinol and its derivatives in cancer treatment and prevention, several more recent large-scale trials have so far failed to show therapeutic benefit.
Developmental and reproductive toxicity: The California EPA’s Proposition 65 list identifies all-trans retinoic acid as a developmental toxicant. It also identifies retinol/retinyl esters as developmental toxicants, but only when daily dosages exceed 10,000 international units. The listing notes that retinol/retinyl esters are required and essential for maintenance of normal reproductive function and that the recommended daily level during pregnancy is 8,000 international units.