Non-cancer health effects of diesel exhaust: A critical assessment of recent human and animal toxicological literature

Abstract

We reviewed laboratory and clinical studies bearing on the non-cancer health effects of diesel exhaust (DE) published since the 2002 release of the US EPA Health Assessment Document for Diesel Engine Exhaust. We critically evaluated over 100 published articles on experimental research, focusing on their value for predicting the risk of non-cancer health effects in humans exposed to DE. Human controlled-exposure studies provide new evidence of lung inflammatory effects and thrombogenic and ischemic effects of inhaled DE, albeit for older-model diesel engines and concentrations that are much higher (~300 μg/m³) than typical ambient or even occupational levels. Recent animal studies provide insight into the potential mechanisms underlying observed respiratory and cardiovascular health responses; however, because of unrealistically high DE concentrations, the mechanisms elucidated in these studies may not be relevant at lower DE exposure levels. Although larger in number, and suggestive of possible mechanisms for non-cancer health effects at elevated DE levels, interpretation of this recent group of clinical-study findings and laboratory-animal results remains hindered by inconsistencies and variability in outcomes, potentially irrelevant DE-exposure compositions, limitations in exposure protocols and pathways, and uncertainties in extrapolation and generalization. A mechanism of action that allows reliable prediction of adverse health effects at DE-exposure levels typical of the present-day ambient and occupational environment has not emerged. Because of changing diesel-engine technology, inhalation studies using realistic environmental and occupational exposures of new-technology diesel exhaust are of critical importance.

Acknowledgments

This review was prepared by T. W. Hesterberg and W. B. Bunn in the course of their employment with the Navistar, Inc., and by C. M. Long, P. A. Valberg, and S. N. Sax at Gradient Corporation and Charles A. Lapin at Lapin & Associates, as consultants to Navistar, Inc. Many thanks to Roger O. McClellan and Thomas Slavin for their insightful reviews and comments on the manuscript prior to its submission.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes

^1. We provide an update of non-cancer health effects of DE, but the Diesel HAD also critically examined the epidemiological and toxicological evidence for DE cancer risks, concluding that DE is “likely to be carcinogenic to humans by inhalation”. Although the US EPA considered the totality of the health effects evidence (e.g. human, animal, and supporting studies) to be supportive of a carcinogenic risk from environmental DE exposures, the Agency concluded that neither human exposure-response data nor laboratory animal data were sufficiently reliable to derive a quantitative estimate (i.e. a unit risk) that could be zero (US EPA, 2002; Hesterberg et al., 2005, 2006).

^2. This RfC was derived from a 70-year-duration human equivalent concentration of DEP corresponding to a NOAEL of 144μg/m³. Application of an uncertainty factor of 30 brings this NOAEL down to an RfC of 5μg/m³.

^3. As discussed earlier, the current (2002) US EPA chronic RfC was set about 30-fold below the lifetime human-exposure-equivalent concentration, NOAEL.

^4. Recent experiments suggest a chronic NOAEL level in the range of 200–1,000μg/m³ DEP, and 500μg/m³ would be about 2 orders of magnitude above 5μg/m³.