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 (approximately 300 microg/m(3)) 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.

Particulate Matter in New Technology Diesel Exhaust (NTDE) is Quantitatively and Qualitatively Very Different from that Found in Traditional Diesel Exhaust (TDE)

“…Controlled-Exposure Studies As discussed in a previous review, 81 human controlledexposure studies are considered to provide some of the most relevant data for assessing the potential health risks of DE exposure given that they directly study human subjects, use well-defined exposure concentrations and durations, and precisely measure health outcomes including subtle biological responses. We identified only a single peer-reviewed journal publication of human clinical data of relevance to NTDE, as well as two abstracts from the same research team.…”

Engine-Operating Load Influences Diesel Exhaust Composition and Cardiopulmonary and Immune Responses

“…Potential cancer risks remain of interest, but studies involving experimental exposures of humans and animals now focus predominantly on a broad range of noncancer effects (Hesterberg et al 2009; Mauderly and Garshick 2009). …”

Assessment of Workplace Diesel Exhaust Exposure and Health Effects

“…Chronic-exposure, animal inhalation studies show a spectrum of dose-dependent inflammation and histopathological changes in the lung in several animal species, including rats, mice, hamsters, and monkeys [3,[25][26]. Human studies have demonstrated exacerbations of chronic bronchitis and chronic obstructive pulmonary disease [17].…”

“…Diesel exhausts vary significantly in chemical composition and particle size between different engine types (heavy duty vs. light duty), engine operating conditions (idle, accelerate, decelerate) and fuel formulations (high/low sulfur fuels) [8]. Although advances in technology have seen a reduction in the amounts of toxic emissions, toxicologically relevant components (PAH, nitro PAH) persist [3].…”

“…Diesel exhaust has been classified as 'probably carcinogenic to humans' [1][2], and has been associated with respiratory, allergic, cardiovascular and reproductive effects in both animal and human studies [3]. The potential effects of ambient diesel exhaust exposure is of great interest, especially as the use of diesel engine technology continues to grow across the world, with the recognition that diesel engine technology can reduce greenhouse gas emissions, compared to other fuels [4].…”