High dose used in chronic toxicity testing that is expected on the basis of an adequate subchronic study to produce limited toxicity when administered for the duration of the test period. It should not induce: (a) overt toxicity, for example appreciable death of cells or organ dysfunction, or (b) toxic manifestations that are predicted materially to reduce the life span of the animals except as the result of neoplastic development or (c) 10% or greater retardation of body weight gain as compared with control animals. In some studies, toxicity that could interfere with a carcinogenic effect is specifically excluded from consideration.