retinol-acetate and Pheochromocytoma

The carcinogenicity of retinol acetate [(RAC) CAS: 127-47-9], a synthetic derivative of retinol, was tested by continuous oral administration in the drinking water of F344/DuCrj rats for 104 weeks. Groups of 50 male and 50 female rats were given solutions of 0.25 or 0.125% RAC in the form of gelatinized beadlets suspended in distilled water. Control groups consisting of the same numbers of rats were given 0.25% of placebo beadlets. All of the surviving animals were killed at 108 weeks, 4 weeks after the cessation of the RAC treatments. The survival rates were 72-84% and were sufficiently high for statistical comparison of all groups. Inhibition of body weight gain was marked in females of the high-dose group. Higher incidences of malignant pheochromocytomas, benign pheochromocytomas, and hyperplasias of the adrenal medulla were observed in the RAC-treated groups. The combined incidences of tumors of the adrenal medulla in males and females of the high-dose groups and the incidence in females of the low-dose group were significantly higher than the incidence in the controls. Conversely, statistically significant decreases were found in the incidences of the mammary gland tumors in males of the high-dose group, of thyroid tumors in females of the high-dose group, and of clitoral gland tumors in females of both high- and low-dose groups. It was concluded that RAC given orally possesses potential for increasing the incidence of pheochromocytomas in male and female F344 rats in a dose-related manner under the conditions of this bioassay.

Topics: Adrenal Gland Neoplasms; Animals; Blood; Body Weight; Diterpenes; Dose-Response Relationship, Drug; Drinking; Female; Male; Pheochromocytoma; Rats; Rats, Inbred F344; Retinyl Esters; Sex Factors; Vitamin A