High incidences of pheochromocytomas after long-term administration of retinol acetate to F344/DuCrj rats.
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.
D000310:Adrenal Gland Neoplasms / Q000139:chemically induced*; D000818:Animals; D001769:Blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005260:Female; D008297:Male; D010673:Pheochromocytoma / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D000084562:Retinyl Esters; D012737:Sex Factors; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000633:toxicity
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate