Proliferative bone lesions in rats fed a diet containing glucocorticoid for up to two years.
A glucocorticoid was fed in the diet to 50 Sprague-Dawley rats/sex at 0, 0.03, 0.06, 0.12, 0.25, 0.50, and 1.0 mg/kg/day for up to 2 yr. A total of 1,400 rats were examined. Bone neoplasms (5 osteosarcomas and 2 osteomas), involving the head, occurred in 7 males that were fed the test compound at the highest dose (0.25 mg/kg) with long-term survivors. One osteoma and 1 hyperostotic lesion were seen in 2 males receiving lower doses (0.06 mg/kg and 0.12 mg/kg, respectively); 1 female rat that received the highest dose (1 mg/kg) had an osteosarcoma. The results suggest, but do not confirm, a relationship between glucocorticoid exposure and bone proliferations in male Sprague-Dawley rats. Other proliferative bone lesions included hyperostosis in a 0.12-mg/kg male, osteoma in a 0.06-mg/kg male, and osteosarcoma in 1 female at 1.0 mg/kg. The purpose of this report is to characterize the incidence and morphology of primary bone proliferative lesions found in rats of 1-yr glucocorticoid toxicity and 2-yr carcinogenicity studies conducted in our laboratory.
Zwicker
G M
GM
Dow Chemical Company, Indianapolis, Indiana 46268, USA.
Eyster
R C
RC
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001859:Bone Neoplasms / Q000139:chemically induced*; D004032:Diet; D005260:Female; D015576:Hyperostosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D010016:Osteoma / Q000139:chemically induced* / Q000473:pathology; D012516:Osteosarcoma / Q000139:chemically induced* / Q000473:pathology; D011282:Pregnenediones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; C021988:deflazacort