A critical assessment of studies on the carcinogenic potential of diesel exhaust.

After decades of research involving numerous epidemiologic studies and extensive investigations in laboratory animals, a causal relationship between diesel exhaust (DE) exposure and lung cancer has not been conclusively demonstrated. Epidemiologic studies of the transportation industry (trucking, busing, and railroad) show a small elevation in lung cancer incidence (relative risks [RRs] generally below 1.5), but a dose response for DE is lacking. The studies are also limited by a lack of quantitative concurrent exposure data and inadequate or lack of controls for potential confounders, particularly tobacco smoking. Furthermore, prior to dieselization, similar elevations in lung cancer incidence have been reported for truck drivers, and in-cab diesel particulate matter (DPM) exposures of truck drivers were comparable to ambient highway exposures. Taken together, these findings suggest that an unidentified occupational agent or lifestyle factor might be responsible for the low elevations in lung cancer reported in the transportation studies. In contrast, underground miners, many of whom experience the highest occupational DPM exposures, generally do not show elevations in lung cancer. Laboratory studies must be interpreted with caution with respect to predicting the carcinogenic potential of DE in humans. Tumors observed in rats following lifetime chronic inhalation of very high levels of DPM may be attributed to species-specific overload mechanisms that lack relevance to humans. Increased tumor incidence was not observed in other species (hamsters or mice) exposed to DPM at very high levels or in rats exposed at lower levels (99% reduction in DPM and other quantitative and qualitative changes in the chemical and physical characteristics of diesel exhaust. Thus, the current database, which is focused almost entirely on the potential health effects of traditional diesel exhaust (TDE), has only limited utility in assessing the potential health risks of new-technology diesel exhaust (NTDE). To overcome some of the limitations of the historical epidemiologic database on TDE and to gain further insights into the potential health effects of NTDE, new studies are underway and more studies are planned.

Indices of fiber biopersistence and carcinogen classification for synthetic vitreous fibers (SVFs).

It is generally accepted that the biopersistence of a synthetic vitreous fiber (SVF) is an important determinant of its biological activity. Experimental protocols have been developed to measure the biopersistence of an SVF from short-term inhalation experiments with rats. Clearance kinetics of long (>20 microm) fibers (those believed to have greatest biological activity) have been approximated by one- or two-pool models. Several measures or indices of biopersistence have been proposed in the literature of which three, the weighted half-time (WT(1/2)), the time required to clear 90% of long fibers (T(0.9)), and the so-called slow-phase half-time (T(2)), have been investigated in some detail. This paper considers both one- and two-pool models for long fiber clearance, characterizes the properties of these candidate indices of fiber biopersistence, identifies measures with potentially superior statistical properties, suggests possible cutoff values based on the relation between biopersistence and the outcome of chronic bioassays, and offers comments on the selection of efficient experimental designs. This analysis concludes that WT(1/2) and T(0.9) are highly correlated, are efficient predictors of the outcome of chronic bioassays, and have reasonable statistical properties. T(2), although perhaps attractive in principle, suffers from some statistical shortcomings when estimated using present experimental protocols. The WT(1/2) is shown to be directly proportional to the cumulative exposure (fiber days) after the cessation of exposure and also the mean residence time of these fibers in the lung.