The Setting of Particulate Exposure Levels for Chronic Inhalation Toxicity Studies

Abstract

This paper briefly reviews the development of regulatory agency guidelines for toxicity testing and the impact of the maximum tolerated dose (MTD) concept on chronic study designs within and outside of the regulatory arena. From the orientation of an inhalation toxicologist, the MTD is viewed as a difficult and costly concept to implement and one that is generally inappropriate as a general basis for setting dust exposure levels in sub-chronic and chronic inhalation toxicity studies. Two possible alternatives are discussed, especially in the context of accumulating evidence that most dusts, even the most innocuous, when presented in excessive amounts produce a spectrum of pulmonary responses that cannot be dissociated from injury.