Assessment of human risks from exposure to low toxicity occupational dusts

Recent animal studies have demonstrated three separate and distinct mechanisms by which low toxicity dusts can cause important chronic pulmonary effects; through overloading of clearance mechanisms, through increased toxicity associated with ultrafine particle size or by increasing the toxicity of known carcinogens in mixed exposures. The problem to be addressed is how the pathogenicity to man of various airborne dusts should be evaluated, when epidemiological evidence is often insufficient, and the reliability of extrapolation of quantitative risks from animals to man is not established. In this paper we examine the feasibility 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 inflammation and fibrosis; (2) postulating that these relativities apply quantitatively 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 consistently in animal studies for the measurement of impairment of clearance leading to overload and resulting inflammation and fibrosis; (2) the quantitative relationships between impairment of clearance leading to overload, and resulting inflammation and fibrosis, can be defined adequately in animals for various dusts; (3) the particle size distributions, including those in the ultrafine range, for dusts to which animals and/or humans are exposed, are taken into account (or are comparable); (4) at least two reference dusts with well-documented activities spanning 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 possible candidate reference and test dusts are identified.