Spring Intro 2023

22/03/2023

What Types of Toxicology Studies are Done?

Computer and Cell based Toxicity Screening Tests

Acute, Subchronic & Chronic Toxicity Tests Determine effect of chemical on health and mortality during various lengths of exposure Developmental Toxicity Tests (teratogenicity) Evaluate the capacity of a chemical to cause abnormalities in embryo and fetus Reproductive Toxicity Tests Assess the effect of a chemical on fertility and fecundity Toxicokinetic Tests Explore the absorption, distribution, metabolism, storage and excretion of a chemical Carcinogenicity Tests Examine the potential of a chemical to cause benign or malignant tumours, shorten the appearance of spontaneous tumours or increase their multiplicity

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Basics of Toxicology Testing for Human Safety Evaluation

1. Do toxicity tests before clinical studies 2. Different approaches for small molecules, biologicals and advanced therapies 3. Use higher levels of the drug than humans will experience 4. Check higher exposure does not cause serious or irreversible toxicity 5. Show “Safety Margin”: that exposure in animal tests at 5-fold > than that in humans is safe, i.e. is a “no effect level” 6. Presume that serious toxicity in animals does predict human toxicity, unless PROVEN otherwise (need information on the mechanism of toxicity) 7. Safety data must justify proposed human exposure The “3Ms” : 1 st , Margin of safety 2 nd , Monitorable early toxicity 3 rd , Mechanism to explain why animal toxicity isn’t human relevant

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