Acute Toxicity Testing in Drug Safety Evaluation

ACUTE TOXICITY TESTING IN DRUG SAFETY EVALUATION 

In the pharmaceutical industry, acute toxicity testing has uses other than for product safety determinations. First, as in other industries, acute toxicity determinations are part of industrial hygiene or occupational health environmental impact assessments (Deichmann and Gerarde, 1969). These requirements demand testing not only for finished products but frequently of intermediates as well. These issues and requirements, however, are discussed in Chapter 2 and are not directly addressed here. 

Another use, now almost abandoned except for in natural product-derived chugs, is in quality control testing or batch release testing. The latter was once a mandated part of the standardization process for antibiotics, digoxin and insulin in the U.S. 

in range-finding tests, the endpoint is simply to determine what is the maximum dosage that can be given without killing an animal. There are numerous designs available for obtaining this information that minimize the expenditure of animals and other resources. 

FIGURE 5.1. Example of typical dosage probe protocol. 

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It is important to use different doses of a chemical or drug to evaluate chemical safety vis-a-vis skin toxicity. Dose levels to be tested for acute dermal toxicity in animals should be sufficient in number, (e.g., three or more and spaced appropriately to produce test groups with a range of toxic effects and mortality rates). The data should permit an acceptable determination of LD50. 

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