ASSESSMENT OF HUMAN RISKS FROM EXPOSURE TO LOW TOXICITY OCCUPATIONAL DUSTS

Recent animal studies have demonstrated three separate and distinct me chanisms by which low toxicity dusts can cause important chronic pulmo nary effects; through overloading of clearance mechanisms, through inc reased toxicity associated with ultrafine particle size or by increasi ng the toxicity of known carcinogens in mixed exposures. The problem t o be addressed is how the pathogenicity to man of various airborne dus ts should be evaluated, when epidemiological evidence is often insuffi cient, and the reliability of extrapolation of quantitative risks from animals to man is not established. In this paper we examine the feasi bility of evaluating the likely human risks of low toxicity dusts by: (1) semi-quantitative comparisons of the ability of various dusts, in animal studies, to cause overload of clearance and resulting inflammat ion and fibrosis; (2) postulating that these relativities apply quanti tatively to human risks; and (3) estimating approximate human risks by comparisons with reference dusts for which adequate animal and human data are available. Such a decision-making framework appears feasible, provided: (1) comparable and quantitative methods are used consistent ly in animal studies for the measurement of impairment of clearance le ading to overload and resulting inflammation and fibrosis; (2) the qua ntitative relationships between impairment of clearance leading to ove rload, and resulting inflammation and fibrosis, can be defined adequat ely in animals for various dusts; (3) the particle size distributions, including those in the ultrafine range, for dusts to which animals an d/or humans are exposed, are taken into account (or are comparable); ( 4) at least two reference dusts with well-documented activities spanni ng the range of toxicity can be identified; and (5) the reliability of the predictions of human pathogenicity of a sample of other dusts is tested, in toxicological studies and by observation in humans. Some po ssible candidate reference and test dusts are identified. (C) 1997 Bri tish Occupational Hygiene Society. Published by Elsevier Science Ltd.