Cancer Council Australia

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Health impacts of particulate matter in diesel emissions


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kNOw cancer risks at work, Cockle Bay Sydney, May 2015



Neil Hime, Epidemiology Research Group, The Woolcock Institute of Medical Research



Health impacts of particulate matter in diesel emissions


Presentation outline:

Dr Neil Hime discusses the scientific evidence of the health effects associated with exposure to particulate matter air pollution in diesel exhaust emissions, with a focus on cancer.

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I am probably going to go over a little bit of what Allan had talked about and I might come to a slightly different conclusion, so maybe we need to chat afterwards.

I know that today is a day about work exposures, but I would like to talk a little bit about environmental exposures as well. And I am even going to go further than that just to give this some context, and that is just to talk briefly about particulate matter in general, but that will be very brief.

So, I am talking about diesel exhaust, which we have already heard is made up of particulate matter and also various gasses, and is a complex mixture that at least includes more than 40 substances that are listed by US EPA as hazardous air pollutants. And 15 of these are listed by the International Agency for Research Cancer as carcinogenic to humans or possible human cacrinogens. I am only going to be talking about the particulate matter today, but chemical reactions in the atmosphere with some of the gasses which are emitted in diesel exhaust result in the secondary generation of PM, and these particulates have been shown to have carcinogenic properties.

Now, I said I just wanted to give this a little bit of context, so I will just talk very briefly on the health impacts of particulate matter. This is ambient PM in general. Strong associations with increasing mortality, respiratory health effects and cardiovascular health effects are generally impacting already existing disease that people have. Exposure to ambient PM has been associated with cancer and also central nervous systems effects and developmental effects. The associations are strongest for mortality and respiratory and cardiovascular morbidity, and I think most people in the area now accept that those outcomes are causal to exposure to ambient PM.

Now, the global burden of disease study, which was a large study that looked at comparative risk assessment of 67 health risk factors and their unit of measure was DALYs, disability adjusted life years; you can think of one DALY as one lost year of healthy life and so combines measures of both years of life lost and years living with a disability. Now, on a world scale here, we see the top 10 risk factors and ambient PM pollution came in at number 9, but both because of different exposure levels and different health problems around the world, you can see that while it ranked 9th in the world, it was 4th ranked in East Asia, and in Australasia it was 26th ranked. But by any measure though, it is a considerable health risk to most of the population of the world.

Now, when it comes to cancer in particular, there is reasonable evidence of association between ambient PM exposure. The three studies I have listed here, American Cancer Society, Harvard Six Cities and Nurses? Health Studies - they are very big cohort studies from the United States and they found significant associations between outdoor PM 2.5 - so that is particles 2.5 micrometers in diameter or smaller - and lung cancer incidence and mortality. And importantly, all studies adjusted for the greatest risk for lung cancer being smoking. Another study in Europe, which was across 17 separate cohorts, found that a 10 mcg/m increase in personal exposure to outdoor air PM 2.5 and PM 10 was significantly associated with increases of 40% and 22% in lung cancer incidence.

This led the IARC to conclude that outdoor air pollution is a cause of cancer deaths in 2013. They said that there was sufficient evidence to conclude that exposure to outdoor air pollution causes lung cancer. It was positively associated with an increased risk of bladder cancer as well, but the strength of evidence it was concluded was not strong enough give a causal relationship. The findings regarding carcinogenicity of outdoor air pollution and as a mixture of PM specifically are remarkably consistent. That came from the IARC.

So, now, let me just bring it back to diesel exhausts. We have already have said what the particulates are. They are a mixture of elemental carbon surrounded by various chemicals, but what stands out are organic compounds - sulphate, nitrate, metals and other trace elements, including toxics polycyclic aromatic hydrocarbons and their derivatives and some metals namely chromium and nickel, which are known to have mutagenic and carcinogenic properties. By saying ?known?, that means that there have been some studies, perhaps animal, sometimes cell studies that show they have the potential to be carcinogenic.

So, diesel exhaust particles from modern engines are primarily these fine particles and they include considerable component of ultrafine, so less than 0.1 micrometer. The PM 2.5 do penetrate deep into lungs and the PM 0.1 has been shown to cross from airways into the blood at least in animal studies I should say. I am not sure that that has been confirmed in humans.

So there is strong evidence that exposure to outdoor air PM is associated and likely causal for health effects including lung cancer, and the chemical composition and size of diesel exhaust particles suggest that these particles have the potential to cause health effects including cancer. So what does the evidence say? Allan alluded to this in regards to animal and cell culture studies, but there are many studies that are showing that diesel exhaust PM causes DNA damage and lung tumours unit dose response manner.

Now, I have chosen, I think some different examples than Allan had regarding epidemiology studies. So there was a meta-analysis conducted, which provided estimates of the relative risk of developing lung cancer and occupations with substantial exposure to diesel exhaust and that is compared to the absence of such exposure. The studies allowed for what is said as adequate latency period, at least 10 years. You could argue whether one that was 10 years as adequate a latency period after exposure. For this particular meta-analysis, mining occupations were excluded because of the potential confounding by other exposures such as silica and arsenic. So, the occupations included were truck drivers, railway workers, mechanics and professional drivers. So, excluding studies where exposure to diesel exhaust could not easily be distinguished from other engine exhaust exposures, occupations with substantial exposure to diesel exhaust were associated with a 47% increase in relatives, so not absolute, smoking-adjusted risk of lung cancer. There was suggestive evidence of exposure response relationship to support occupational diesel exhaust exposure being causative for lung cancer.

Another large study of over 12,000 mine workers in the United States, from non-metal mines, found that diesel exhaust exposure, which was measured, as often is in these studies from work histories, although this one did also include air measurements at mine sites, which I think is important. They found that it was positively associated with lung cancer mortality. A cohort study retrospective looking at some historical data, found that exposure response relationship for lung cancer mortality was demonstrated in US railway workers. The relationship was only evident in workers that were hired after 1954, the year that diesel locomotives were introduced. The US EPA in 2002, Allan alluded to this too, in their first health assessment document for diesel engine exhaust, they concluded that long-term inhalation exposure is likely to pose a lung cancer hazard to humans. And of course, it has already been mentioned that in 2012, the IARC classified diesel engine exhaust as carcinogenic to humans. So, what the IARC stated was that diesel engine exhaust causes cancer of the lung and a positive association was observed between exposure to diesel engine exhaust and cancer of the bladder.

So, the dose response relationship cited by the IARC support exposure to diesel exhaust being causative for lung cancer and most importantly, the exposure lung cancer risk associations remained after results were adjusted for smoking. The conclusion of the IARC report was based on evidence from studies of cohorts of workers exposed in their occupations. It was also from case control studies in occupationally exposed populations and also case control studies in the general population, but again the exposure to diesel exhaust was estimated from occupational exposure of these people in the general population and from animal studies. The IARC report did not include evidence from studies of non-occupational exposures, and the reasoning was that the ambient pollution comprises emissions from many sources. And the IARC stated at present it is very difficult to assess the specific contributions of these sources to the observed cancer risk. These environmental studies would contribute little information in addition to the studies reviewed.

Now, there has been some criticism of the report only because the conclusions of the report are not meant to be limited to occupational exposures alone, but many people say if the evidence has almost all come from occupational exposure, you can't say that environmental exposure is going to cause the same outcomes. So, not withstanding that risks identified in heavily exposed occupational groups could receive positive findings in the general population. I would say that currently the health risks of environmental (so now we are talking non-occupational exposures to diesel exhaust) are largely unknown. The evidence from occupational exposure used by the IARC relates to the whole diesel exhaust mix of gasses and particles. Generally, the only evidence specific to diesel exhaust PM comes from animal and cell culture studies and a few controlled exposure studies in humans.

However, as Allan said, it is not all entirely clear. Not all investigations support diesel exhaust exposure causing cancer. A systematic review conducted since the publication of the IARC report concluded that neither 42 cohort studies nor 32 case control studies indicated a clear exposure response relationship. And it was the lack of objected measures of exposure cited as the main problem with the evidence, with exposure assessment usually based on work histories and not direct measures of exposure.

It has also been suggested that occupational epidemiological evidence based on weak exposure response associations could be explained by biased confounding charts or exposure misclassification.

So, I wouldn't say all the evidence is in one direction, however the majority of the epidemiological evidence suggests a causal relationship exists between occupational diesel exhaust exposure and the incidence of lung cancer.

I have talked only about cancer, but there are other health effects of course, as Allan alluded to, associated with diesel exhaust exposure. So occupational exposures have been associated with cough, chest tightness, wheezing, chronic bronchitis and decreased lung function. Controlled exposures in human volunteers has adverse cardiovascular effects on heart rate, blood pressure and clotting mechanisms and respiratory effects with inflammation and airway resistance, as well as enhanced immune responses and eye and nasal irritation. Exposures of animals to diesel exhaust PM has been shown to progress influenza and other viral infections, and enhanced allergic response to pollen and dust mites, as well as increased atherosclerosis in an animal model of cardiovascular disease, and result in adverse birth outcomes when pregnant animals were exposed.

Finally, I am just going to conclude with a shameless plug for a report that is going to come out on the evidence of the health impacts of source specific PM. Now, this was for New South Wales EPA, New South Wales Health, but it is going to be made available publically and it does include chapters on the health effects of on-road and non-road diesel exhausts. The report was to look at environmental exposures, but because of the evidence that I have presented today on those chapters, it was primarily occupational exposures that we did have to refer to, to determine what we felt were the effects of PM from this specific source. But you know, I would add you can't apply results from occupational studies directly to the wider population, because the wider population includes a lot of people which are very different to the workers and their levels of exposure will be somewhat different.

That's all, thank you.

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