Time-related changes in the incidences of spontaneous neoplasms in skin (fibroma 
and keratoacanthoma), thyroid (C-cell and follicular cell adenomas/carcinomas), 
uterus (stromal polyp), testes (Leydig cell tumor) and hemolymphoreticular 
system (mesenteric lymph node hemangioma and malignant granular lymphocytic 
leukemia) were assessed statistically in Wistar, Sprague-Dawley and F344 rats 
employed by the BASF, Germany and major European contract research organizations 
over the last 20 years. Negative trends (5 out of 80 cases) were observed for 
skin fibromas in F344 males, for follicular cell adenomas in Han Wistar females 
and in Sprague-Dawley males and females, and for follicular cell carcinomas in 
Sprague-Dawley males. Positive trends (8 out of 80 cases) were observed for skin 
keratoacanthomas in Han Wistar males, for C-cell adenomas in BASF Wistar males 
and females, for stromal polyps in Han Wistar and Sprague-Dawley females, and 
for mesenteric lymph node hemangiomas in Han Wistar and Sprague-Dawley males and 
in BASF Wistar females. In 67 out of 80 cases there were no statistically 
significant trends. Tumor drift was not common but occurred far more often in 
outbred rat strains (Wistar and Sprague-Dawley) than in the inbred rat strain 
(F344). This observation suggests that tumor predisposition is genetically 
determined, that tumor drift is primarily caused by genetic drift and that 
non-genotoxic carcinogens operate by facilitating the expression of tumor 
predisposition in target cells.