Health studies on Diesel Exhaust (DE) have investigatedemissions from older diesel engines and do not reflectthe potential health effects from current new technologydiesel engines. Epidemiological studies and extensiveinvestigations in laboratory animals, have notconclusively demonstrated a causal relationship betweenDE exposure and lung cancer. Relatively high levels ofDiesel Particulate Matter (DPM) can elicit a mild,transient inflammatory response in the lung. Animalstudies reported variable and inconsistent inflammatorychanges. Human studies at high DE exposures suggestpossible thrombogenic and ischemic effects. Somefindings in animals were suggestive of potentialreproductive responses at very high DE exposures.Chronic inhalation exposures with animal species foundno adverse effects at levels 10-30 times higher thanambient DE levels.
INTRODUCTION
In the past two decades, dramatic changes in dieselengine technology have resulted in > 99% reduction inDPM from unregulated Traditional DE or TDE (pre 1988engines) to current new technology DE or NTDE (post2007 engines) (Fig. 1) [1]. Nitrogen oxides (NOx)emissions experienced a similar decline between TDEto NTDE (Fig. 2). In addition emissions of other
regulated compounds, volatile organic compounds,aldehydes, and polycyclic aromatic hydrocarbons aresubstantially lower in NTDE (Fig. 3 to 5).
Figure 1 : Reductions in DPM Emissions
Figure 2 : Reductions in NOx Emissions
Figure 3 : Reductions in Regulated Emissions
Figure 4 : Reductions in Volatile OrganicCom-pounds and Aldehyde Emissions
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Thus, the current database, which is focused almostentirely on the potential health effects of unregulatedTDE or transitional phase DE (1988-2006), has onlylimited utility in assessing the potential health risks ofNTDE. To overcome some of the limitations of thehistorical epidemiologic database on TDE and to gainfurther insights into the potential health effects of NTDE,new studies are underway and more studies areplanned.
HEALTH EFFECTS STUDIES
EPIDEMIOLOGICAL STUDIES : Studies oftransportation industry (trucking, busing and railroad) showa small elevation in lung cancer incidence (risk ratiosgenerally below 1.5) [2]. Lung cancer rates did notincrease with increasing duration of employment orexposure. Thus a dose response for DE was lackingand no causal relationship between DE and lung cancerhas been clearly demonstrated. The studies are alsolimited by a lack of quantitative concurrent exposuredata and inadequate or lack of controls for potentialconfounders, particularly tobacco smoking. Furthermore,prior to dieselization, similar elevations in lung cancerincidence have been reported for truck drivers (Fig. 6).These findings suggest that an unidentified occupationalagent or lifestyle factor might be responsible for the lowelevations in lung cancer reported in the transportationstudies. In contrast, underground miners experience thehighest occupational exposures to DPM (Table- I) butdo not show elevations in cancer (Fig. 7).
Figure 5 : Reductions in Polycyclic AromaticHydro-carbon (PAH) Emissions
Table- I : Occupational Exposures to DPM
Figure 6 : Lung Cancer Risk in Truck Drivers
Figure 7 : Lung Cancer Risk in Underground Miners
LABORATORY STUDIES : Laboratory studies must beinterpreted with caution with respect to predicting thecarcinogenic potential of DE in humans [3]. Life-spanbioassays in rats, mice, and hamsters demonstrated thatchronic inhalation of high concentrations of DE causedlung tumors in rats but not in mice or hamsters. Athreshold level may be occurring as no excess lungtumors were observed below this exposure level (Fig. 8).Subsequent research has shown that similar chronic highexposures to particulate matter generally consideredinnocuous (such as carbon black and titanium dioxide)
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also caused lung tumors in rats. This appears to be theresult of an overloading of the lung clearance of particleswhich leads to a build up of particles in the lung,sustained inflammation and cell proliferation, andeventually lung tumors. This mechanism of action wouldnot be expected to occur in humans exposed underoccupational or ambient conditions. Thus, in 2002, theU.S. Environmental Protection Agency (US EPA)concluded that the findings in the rats should not beused to characterize the cancer hazard or quantify thecancer risk of DE.
Inflammation and Immune System : Volunteer studiesindicated that DPM concentrations on the order of 100g/m3 are well-tolerated by the lung due to its protectiveantioxidant capacity that prevents the occurrence of lunginjury and inflammation. Results of high DE exposurein asthmatics were variable, with little evidence forenhanced respiratory effects in asthmatics inhaling DE,compared to normal volunteers. Although human studiesexhibit considerable heterogeneity (Fig. 10), perhapsattributable to the source of DPM, the conclusions ofthe human studies suggest that the tested levels ofDPM can elicit a mild, transient inflammatory responsethat is not highly adverse for both healthy individualsand asthmatics.
Figure 8 : Potential Threshold Exposure Level in DEExposed Rats
Mutagenicity Studies : Although DPM containsmutagens, mutagenicity studies in which cells wereexposed to concentrated extracts of DPM also havelimited application to human risk assessment, becausesuch extracts can be obtained from DPM only by usingstrong organic solvents, agitation, and heat. Most studieshave shown that whole DPM itself is not mutagenicbecause adsorbed organic compounds are minimallybioavailable in aqueous based fluids.
NON-CANCER STUDIES : DE exposures in non-cancerstudies with human volunteers are 5 to 10 timeshigher than levels observed in typical ambient conditions(Fig. 9) [4].
Figure 9 : Controlled and Ambient DPM Exposures
Animal studies reported changes in inflammatorymarkers such as immunoglobulin levels, cell infiltrationinto the lungs, cytokine concentrations, reactive oxygenspecies, and susceptibility to infection (Fig. 11).
Figure 10 : Lung Responses in Humans
Figure 11 : Animal Responses to DPM Exposure
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However, the results show considerable variability andinconsistency in allergic responses to DPM acrossanimal species, disease model, study protocol, andparticularly, among different sources of DPM, most ofwhich are “historical” TDE. For example, many studiesconcentrated on observed adjuvant effects of lung-administered DPM, but the results depended critically onthe source of the DPM. Also, inhaled DPMconcentrations were generally quite high, ranging from1,000 to 3,000 to 23,000 �g/m3, and even up to100,000 �g/m3.
Cardiovascular Health Effects : Findings from human-exposure studies suggest thrombogenic and ischemiceffects of inhaled DE, albeit at exposure levels that aremuch higher (~300 �g/m3) than typical ambient or evenoccupational levels. Although possible mechanisms forDE-induced cardiovascular health effects at elevated DEexposures were postulated, further study is needed toidentify any actual mechanisms.
Studies in laboratory animals provide insights on thepotential mechanisms underlying observed cardio-vascular health responses (e.g., abnormal electricalactivity, increase in vascular inflammatory factors,platelet activation), but, given the use of unrealisticallyhigh exposure levels, the mechanisms elucidated inthese studies may not be relevant at lower environmentalDE exposure levels.
Other Health Endpoints : Some findings in animalswere suggestive of potential reproductive responses,such as increased testosterone levels and decreasedspermato-genesis at very high DE exposures, but thereis no evidence of reproductive responses at DE levelsnear the ranges typical of either occupational or ambientenvironments. Several large-scale experiments withanimal species reported on chronic effects of DEinhalation on the respiratory system. The data showedthat highly elevated DPM doses (concentration xduration) can lead to chronic lung inflammation, but atsmaller doses, still much higher than typical levels ofDPM, little was found in the way of adverse orirreversible effects. These recent experiments suggesta chronic No-observable-Adverse-Effect Level (NOAEL)in the range between 200 and 1,000 �g/m3 DPM, whichis somewhat higher than the ~ 150 �g/m3 DPM usedas the basis for setting the DE Reference Concentration(RC) at 5 �g/m3 by the US EPA. Although larger innumber, and suggestive of possible mechanisms fornon-cancer health effects at elevated DE levels,
interpretation of this recent groups of clinical-studyfindings and laboratory-animal results is still hindered byinconsistencies and variability in outcomes, potentiallyirrelevant DE exposure compositions, limitations inexposure protocols and pathways, and uncertainties inextrapolation and generalization. No specific andconsistent mechanism of action has emerged thatsupports established adverse health impacts at DEexposure levels typical of present day ambient andoccupational environments.
CONCLUSION
Emissions from new technology diesel engines, whichare much lower than older diesel engines, need furtherstudy. Despite epidemiological studies and extensiveinvestigations in laboratory animals, a conclusive causalrelationship between DE exposure and lung cancer hasnot been demonstrated. While very high levels of DEmay cause lung inflammation, cardiovascular andimmunological effects, the data suggest that currentambient DE levels do no pose a health concern.
REFERENCES
1. Hesterberg T. W., Lapin C.A and Bunn, W.B. “AComparison of Emissions from Vehicles Fueled withDiesel or Compressed Natural Gas”, Environ. Sci.Technol. 42(17): 6437-6445, 2008
2. Hesterberg T. W., et al., “A Critical Assessment ofStudies on the Carcinogenic Potential of DieselExhaust”, Crit. Rev. Toxicol. 36(9):727-776
3. Hesterberg, T.W., et al., “Carcinogenicity Studies ofDiesel Engine Exhausts in Laboratory Animals: AReview of Past Studies and a Discussion of FutureResearch Needs”, Crit. Rev. Toxicol. 35(5):379-411(2005)
4. Hesterberg, T. W., et al., “Non-Cancer Health Effectsof Diesel Exhaust (DE): A Critical Assessment ofRecent Human and Animal Toxicological Literature”,Crit. Rev. Toxicol. In press, 2008
CONTACT
Charles LapinToxicology ConsultantLapin & AssociatesEmail : [email protected]
