Assessing risks from data on other exposure routes. Possibilities and limitations of using toxicity data derived from...

There is no simple and generally applicable way in which toxicity data derived from one route of exposure can be used to evaluate the effects of exposure by another route in the same species of animal or for risk assessment of another exposure route in man. Reliable predictions may be made in some cases where substances act systemically and have relatively long half-lives and where there are adequate data on toxicity by one route and on pharmacokinetics and metabolism by both routes. Extrapolation may also be possible where it can be shown that the nature and degree of toxicity are directly related to blood or tissue concentrations. The occurrence of toxic effects at the point of exposure (local toxicity) increases the uncertainties associated with extrapolation, usually making it not feasible. The use of safety factors to allow for uncertainties inherent in extrapolating between routes of exposure where data are inadequate is not advocated. Whether an extrapolation of data is justified in an individual case should be decided on a case-by-case basis; generalizations cannot be made.