High @[email protected] used in @[email protected] testing that is expected on the basis of an adequate subchronic study to produce limited @[email protected] when administered for the duration of the test period. It should not induce: (a) overt @[email protected], 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 @[email protected] gain as compared with control animals. In some studies, @[email protected] that could interfere with a carcinogenic effect is specifically excluded from consideration.