Toxicity testing conversion factors

Aside from consideration of drug toxicity, some antimicrobial use requires more in tensive risk-benefit analysis. An example of this is the decision to use isoniazid prophylactically to prevent tuberculosis. Because the hepatotoxicity of isoniazid increases in frequency with age, older persons (>45 years) who are candidates for isoniazid prophylaxis (positive skin test) must have additional risk factors for tuberculosis to balance the potential toxic effects. These include evidence of recent skin-test conversion, immunosuppression, or previous gastrectomy. Older patients without additional risk factors are more likely to suffer toxicity from isoniazid than derive benefit from its use. ... 

The quantitative measurement of toxicity level is expressed by parameters like NOEL (no observed effect level), NOAEL (no observed adverse effect level), and ADI (acceptable daily intake). The NOEL values are divided by 100 to obtain ADI values. The 100 safety factor derives from 10 x 10, where the 10s represent the animal-to-human conversion rate and the human variability factor. Currently, the most useful index of safety is the ADI, expressed as milligrams of test substance per kilogram of body weight (ppm), with the recommendation not to eat more than the ADI per day. The FDA, EU, and WHO agree on the ADI principle. 

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