A major assumption when evaluating the toxicity of drugs or other chemicals is that the findings in animals predict what will happen in humans. This assumption has been in place for many years and more specifically the philosophy for evaluating the safety of drugs in animals before giving them to humans’ dates prior to the 1930s although this was voluntary as there were no laws in place to mandate this review. Following the death of many patients taking elixir of sulfanilamide contaminated with ethylene glycol, Leake (1929) suggested that competitive pressures and a general excitement for discovering new remedies resulted in an urgency where a “reliable scientific” evaluation of new drugs was often overlooked1). His proposal was to standardize the evaluation prior to initiating dosing in humans to include the following assessments:
• Minimal lethal dose
• Influence on isolated organs systems
• Mechanism of general systemic effects
• Fate in body and rate of destruction or elimination
• Acute and prolonged dosing
• Define therapeutic index
From “general systemic studies” Leake proposed
to evaluate “blood constituents, circulatory and respiratory activity, central nervous system and muscular response, glandular and alimentary action, kidney and sexual function and general metabolism”.
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