In a survey of the toxicological profiles of 50 compounds in rodent and non-rodent species, sensitive criteria of toxicity were found to be the simple characteristics, such as clinical observation of the living animal, growth and organ weight analysis, liver and kidney function tests and histological examination of selected tissues. There was poor correlation of target organ toxicity across the species. For this reason safety evaluation should not be based on the demonstration of target organ toxicity, but on the absence of toxic signs. A step by step approach, based on the biological activity of the compound, would provide more meaningful data for safety evaluation than the standard toxicological studies in a rodent and non-rodent species.