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  2. September 2015 Vol. 7 Issue 91

Air Pollution, Disease, and Mortality

Particulate matter as a global health threat

By Walter Crinnion, ND

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The World Health Organization has stated that air pollution accounts for 1.3 million deaths worldwide every year. This article reviews the association of air pollutants with all major causes of death. Those associations understood, it becomes clear that outdoor air pollution is likely to be an even greater cause of mortality across the globe than is currently recognized.

This paper is part of our Environmental Medicine Special Issue. Read the entire issue below.

Abstract

The World Health Organization has stated that air pollution accounts for 1.3 million deaths worldwide every year. This article reviews the association of air pollutants with all major causes of death. With those associations understood, it becomes clear that outdoor air pollution is likely to be an even greater cause of mortality across the globe than is currently recognized.

Introduction

The World Health Organization (WHO) has stated that air pollution accounts for 1.3 million deaths worldwide every year.1 Upon a review of the WHO listing of the leading causes of death (Table 1), one will see that deaths from outdoor air pollutants come in just between tuberculosis and diabetes mellitus.2 This article will review the association of air pollutants with all the major causes of death listed below except diarrheal diseases, HIV/AIDS, tuberculosis, and traffic accidents. Once those associations are understood, outdoor air pollution appears likely to be an even greater cause of mortality across the globe than is currently recognized.

Air Pollutants

Outdoor air is contaminated with a host of vapors, gases, and particulates from combustion (vehicular, industrial, stationary, and natural sources), evaporation, industry, agriculture, and other daily activities during which these substances become airborne. Indoor air has all the same pollutants, to which are added additional toxicants from building materials, furnishings, cooking, cleaning chemicals, and air fresheners, to name a few, making indoor air pollution potentially worse than outdoor. 
 
  Deaths in Millions % of Deaths
Ischemic heart disease 7.25 12.8
Stroke 6.15 6.4
Lower respiratory infection 3.46 6.1
Chronic obstructive pulmonary disease 3.28 5.8
Diarrheal diseases 2.46 4.3
HIV/AIDS 1.78 3.1
Respiratory-tract cancers 1.39 2.4
Tuberculosis 1.34 2.4
Diabetes mellitus 1.26 2.2
Traffic accidents 1.21 2.1

Table 1. Major Causes of Death Compiled From World Health Organization Statistics1

Urban Air Pollution Levels

The major population centers have the greatest amount of air pollutants, mostly due to stationary energy sources and industry, as well as the huge amount of fuel burned to provide transportation. Because of the multiple health problems posed by such pollution, the United States Congress passed the Clean Air Act in 1970, which allowed the federal government to set limits for emissions from stationary and mobile sources of pollution. In May 1971, the Environmental Protection Agency (EPA) was established to implement the mandates of the Clean Air Act. Since 1970, the Clean Air Act has been amended twice (in 1977 and in 1990).3 Part of the original 1970 mandate allowed the newly formed EPA to set national ambient air quality standards for various pollutants. The EPA chose the 6 most common and most damaging pollutants, which are also referred to as “criteria pollutants.” These are particle pollution (often referred to as particulate matter [PM]), ground-level ozone, carbon monoxide, sulfur oxides, nitrogen oxides, and lead. Of the 6 pollutants, particle pollution and ground-level ozone pose the most widespread health threats. These 6 are called criteria air pollutants because their permissible levels are derived from either human health-based and/or environmentally based criteria (science-based guidelines). These criteria are referred to as “primary” when they are based on human health outcomes and “secondary” when they are associated with environmental or property damage.4
 
While all of these 6 criteria pollutants deserve attention, this article will focus PM, the aromatic hydrocarbons it carries, and the illnesses associated with it.

Particulate Matter 

PM (also referred to as particulate pollution) is a combination of liquid droplets (aerosols) and solid particles like dust, soot, smoke, and dirt. Particulates are found in smoke, diesel exhaust, and haze that either come directly from combustion or are products of a reaction between gases and sunlight or air. From a health perspective, PM is differentiated according to particle size.5 The largest of the PM, called coarse particles, are between 10 mm and 2.5 mm and are given the designation of PM10. These are often encountered near dusty roadways and industry. They are known to lodge in the trachea or bronchi. Fine particles are those that are between 2.5 mm and 0.1 mm in diameter and are designated as PM2.5. Fine particles can lodge in the alveoli of the lungs. Ultrafine particles (UFPs), also called nanoparticles, are less than 0.1 mm (100 nm) in size (PM<0.1). Concentrations of atmospheric UFPs are tens of thousands of times higher in urban air than in rural air and are considered the most detrimental of all PM fractions.6
 
UFPs can be either exhaled or absorbed systemically. Absorption of UFPs can pose serious health risks. For example, traffic exhaust UFPs are associated with adverse effects in the respiratory, cardiovascular, and nervous systems, in addition to stimulating oxidative damage and inflammation.7 The 2 major sources of UFPs are cigarette smoke and diesel exhaust; biodiesel puts out even higher UFP levels than regular diesel.8
 
A recent study in Australia sought to find out where children encountered their highest exposures to UFPs. The researchers were initially quite concerned about diesel-powered school buses that often idle outside the school at the end of the school day.6 They discovered that the greatest exposure to UFPs was actually encountered at home (55% of the total daily exposure), with school exposure being the second highest source (35% of the total). Interestingly, it was not the idling buses that provided the greatest exposure to UFPs but rather the urban background levels. The activities that were associated with the greatest exposure to UFPs were outdoor activities (exposure to ambient urban air), cooking and eating in the home, and commuting. 
 
UFPs are small enough to enter the bloodstream and settle in more distant organs than the lungs. For example, UFP levels in the livers of rats 18 to 24 hours after UFP exposure were found to be 5 times higher than the PM levels in their lungs.9 These UFPs can also travel from the nose into the brain via the olfactory nerve.10 UFPs of iron oxide, India ink, and titanium dioxide that were initially identified in alveolar macrophages were found a day later in the lung (in the highest concentration), liver, kidney, heart, tracheobronchial and mediastinal lymph nodes, anterior and posterior nasal cavity, the brain, and the blood. At 4 days postexposure, particles were found in all of the above except for the nasal cavity and brain. At 7 days postexposure, they were still found in the lungs, liver, and blood.11 A group of rats that were exposed only once to UFPs and then sacrificed after either 3 weeks, 2 months, or 6 months showed that the UFP concentrations in the brain, heart, spleen, liver, and lungs from the single exposure slowly reduced over time, with the lungs retaining the most UFP.12 Of course, urban-dwelling humans are exposed daily and are not allowed time to clear the UFP from their organs. 
 
UFPs cause significant oxidative damage in the tissues and organs to which they are distributed.13-15 PM in general has been associated with increased mortality primarily from cardiovascular,16,17 respiratory,18 and neoplastic diseases.19 PM of all sizes act as carriers for a number of other potent air pollutant chemicals, including polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs), which may account for some of their toxic health effects.20

Polycyclic Aromatic Hydrocarbons  

PAHs are highly lipophilic (fat soluble) and therefore are found naturally in oil, coal, and tar deposits. They are also found in the consumer products coal tars, crude oils, creosote, and roofing tar. More than 100 PAHs are formed during the incomplete burning of coal, oil, and gas for fuels; the incineration of garbage; smoking tobacco; or the charbroiling of meat. In short, the burning of anything that is carbon-based may produce PAHs. 
 
Table 2 lists the 17 most common PAHs as well as their carcinogenic rating by the EPA and whether each is present in diesel exhaust. The EPA has determined that benz[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, dibenz[a,h]anthracene, and indeno[1,2,3-c,d]pyrene are probable human carcinogens.21 Benzo[a]pyrene is a known human carcinogen and is the main lung carcinogen in cigarette smoke22 and vehicular exhaust.23 Both PM and PAHs are known to damage mitochondria and suppress their proper functioning.24,25
 
Polycyclic Aromatic Hydrocarbons Probable Carcinogens per US Environmental Protection Agency Present in Diesel Exhaust
Acenapthene    
Acenapthylene   X
Anthracene   X
Benz[a]anthracene X X
Benzo[a]pyrene X X
Benzo[e]pyrene   X
Benzo[b]flouranthene X X
Benzo[j]flouranthene   X
Benzo[k]flouranthene X X
Benzo[g,h,i]perylene   X
Chrysene X X
Dibenzo[a,h]anthracene X  
Flouranthene   X
Flourene   X
Indeno[1,2,3-cd]pyrene X X
Phenanthrene   X
Pyrene   X

Table 2. The 17 Most Common Polycyclic Aromatic Hydrocarbons in Outdoor Air

The table shows that diesel exhaust is a major source of the most common PAHs, including those that are known (benzo[a]pyrene) or probable carcinogens. Benzo[a]pyrene is metabolized by cytochrome P450 1A2 and transformed into a far more toxic metabolite: benzo[a]pyrene epoxide, highly carcinogenic.26

Industrial- and Vehicle-generated Volatile Organic Compounds 

VOCs, also referred to as solvents, are typically short-chain hydrocarbons that evaporate rapidly at ambient temperatures and have a variety of industrial uses.27 VOCs are used in paints, glues, inks, fragrances, and building materials and are found in cigarette smoke, gasoline, and vehicular exhaust. The 4 most common VOCs are benzene, toluene, ethylbenzene, and xylene; they are often referred to simply as BTEX and can account for up to 27% of each gallon of gas dispensed at the pump for every vehicle.28 For the United States as a whole, vehicular emissions are the greatest source of these compounds found in urban and rural air, but in areas of the country where refineries and chemical plants are located, these nonmobile sources far surpass emissions put out by transport vehicles. The EPA website provides information on the total VOC emissions for the entire United States or by state or county. 

Data from the 1990 US EPA Cumulative Exposure Project looked at 148 toxic air contaminants for each of the 30,803 census tracts in the contiguous United States.29 Concentrations of benzene, formaldehyde, and 1,3-butadiene were greater than levels known to cause cancer (cancer benchmark levels) in over 90% of the census tracts. Approximately 10% of the census tracts had 1 or more carcinogenic hazardous air pollutant in concentrations above 1-in-10,000 risk levels. As an example, these data revealed that of 25 sites in Minnesota, 10 pollutants were found that exceeded the benchmarks in 1 or more sites (acrolein; arsenic; benzene; 1,3-butadiene; carbon tetrachloride; chromium; chloroform; ethylene dibromide; formaldehyde; and nickel).30

The Brookhaven Medical Unit in Atlanta, Georgia, an environmentally controlled clinic, has filters of activated charcoal and aluminum oxide impregnated with potassium permanganate to rapidly eliminate fumes and provide less-polluted air for those in the clinic. Yet even in such a tightly controlled unit, at times of peak traffic flow, levels of hydrocarbons, and other exhaust components (carbon monoxide, chlorine dioxide, hydrogen cyanide, nitrogen dioxide, and ozone) were detected in the unit.31
 
A study of cyclists in an urban area showed elevated serum benzene and toluene and elevated toluene and xylenes in the urine after a 2-hour ride. Those riding in urban areas had consistently higher post-ride levels of these compounds than those riding in rural areas (details summarized in Table 3).32
 
  Rural Rides (blood ng/L) Urban Rides (blood ng/L)
  Pre-ride Post-ride Pre-ride Post-ride
Benzene 190.0 188.9 186.1 224.2
Toluene 310.1 320.2 310.3 436.3
Ethylbenzene 232.0 237.0 239.0 292.5
Xylenes 735.0 697.3 831.4 1190.0
  Rural Rides (urine ng/L) Urban rides (urine ng/L)
  Pre-ride Post-ride Pre-ride Post-ride
Benzene 127.6 112.4 104.2 120.5
Toluene 282.0 280.1 295.1 338.3
Ethylbenzene 82.8 86.1 70.1 74.5
Xylenes 210.4 219.0 220.3 251.1

Table 3. Data From Bergamaschi et al: Bicyclist Biomarkers of Internal Dose in Pre-ride and Post-ride Blood and Urine Samples32

Health problems associated with vehicular exhaust include increased mortality, cardiovascular illness, respiratory illness, neurological problems, and endocrine disorders including obesity, diabetes, and infertility.

Mortality

PM, with its attached load of PAH and VOCs, has long been associated with a number of adverse health outcomes, including increased mortality. In studies done in major cities across the globe, within 2 days of increased PM levels, the mortality rates increase.33,34 Recent estimates show that aggressive reductions in global PM production could reduce global annual mortality rates attributed to PM2.5 by 23%.35

Cardiovascular Disease

Many of the deaths associated with higher levels of PM are directly due to acute myocardial infarctions (MI), to which PM is strongly linked. An article in the New England Journal of Medicine in 2004 reported that an association was found between exposure to traffic and the onset of a MI within 1 hour of beginning their morning commute (odds ratio: 2.92).36 The authors attribute at least some of this increase to vehicular exhaust exposure. Six years later, Circulation, the official journal of the American Heart Association, published a statement saying that there is an established causal relationship between exposure to PM2.5 and cardiovascular morbidity and mortality.37 This group also noted that reductions in PM exposure were associated with reduced rates of cardiovascular mortality within just a few years’ timeframe: 
Exposure to PM<2.5µm (PM2.5) over a few hours to weeks can trigger cardiovascular disease-related mortality and nonfatal events; longer-term exposure increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within the more highly exposed segments of the population by several months to a few years.37
 
Yet even with this clear statement by the American Heart Association, the use of measures to reduce PM exposure to prevent the number 1 killer of Americans today has received little or no public exposure. 
 
Carotid intima-media thickness (CIMT) is used as an easily assessed surrogate marker for atherosclerosis and is a strong predictor of future cardiovascular events.38 Each standard deviation increase in CIMT is associated with a 32% increased risk of stroke and a 26% increased risk of MI. In a large study of almost 6,000 adults from 6 different US communities, it was noted that people living with higher home air PM2.5 (from both outdoor and indoor sources) had far greater CIMT progression than those with lower PM2.5 exposure.39 These data corroborated a prior study of adults living in the Los Angeles, California, basin that showed air pollution is associated with progression of atherosclerosis via CIMT testing.40
Air is vital for human life, with the average adult breathing in over 17,000 times every day. Unfortunately, with very few exceptions, each of those daily breaths may come with a substantial number of toxicants with severe health consequences.
CIMT has been directly linked with PAH levels as well. A study of Brazilian cab drivers and non‒cab driving controls measured 1-hydroxypyrene (1-OHP), a common metabolite of traffic-related PAH compounds and a validated marker for PAH exposure, along with other indices of cardiovascular inflammation and disease.41 The taxi drivers had significantly higher levels of 1-OHP along with higher levels of oxidized low-density lipoprotein (LDL), homocysteine, high-sensitivity c-reactive protein, and other proinflammatory cytokine markers. The researchers also reported that the taxi drivers had significantly lower levels of glutathione peroxidase and glutathione transferase function, as well as lower levels of ascorbic acid. This group of researchers then took the study 1 step further and looked at the level of atherosclerosis that was present in the drivers and controls to see how that related to all of these other markers.42 This was the study in which 1-OHP was directly linked with not only serum homocysteine levels, but also greater CIMT. Interestingly, the CIMT was not associated with total cholesterol, triglycerides, or LDL levels.
 
Hypertension is a major risk factor for both stroke and heart attack, as well as increased morbidity to other organs in the body; it is also clearly associated with air pollution levels.43 Long-term exposure to elevated levels of all PM sizes leads to an elevation in diastolic blood pressure in both adults and children.44,45 Interestingly, this effect is heightened in people who are obese46 and who are psychologically stressed,47 while the effect is reduced in those children who were breastfed.48 Not only can vehicular exhaust particulate matter levels increase diastolic blood pressure, but biological PM49 (commonly found in indoor air) and the use of biomass fuel can do the same.50

Respiratory Illness

It has long been established that children have far higher rates of asthma, bronchitis, bronchiolitis, pneumonia, phlegm production, and wheezing when exposed to vehicular exhaust.51 Several studies have looked at the rates of respiratory disease in those living close to busy roadways vs those who live farther from main thoroughfares. All such studies have confirmed that the closer one is to a higher level of vehicular exhaust (especially diesel truck exhaust), the greater the risk of asthma.52,53 One of the largest studies to date to explore the association between air pollution and respiratory disease is the European Study of Cohorts for Air Pollution Effects project, which encompasses 10 European birth cohorts in 6 countries with a total of 16,059 children.54 The authors found that exposure to air pollution clearly increased the risk of pneumonia in the children they followed.
 
While respiratory and cardiovascular effects of air pollution have long been associated with mortality, recent studies are linking it to a number of other issues, including neurological and endocrine issues. 

Neurological Effects

Exposure to vehicular exhaust has been clearly linked to reduced cognitive functioning in both children and adults. In adults, it has been associated with depression, and in children, it may influence the risk and severity of autistic spectrum disorder. Prenatal exposure to PAH compounds from vehicular exhaust leads to reduced intelligence quotient (IQ) levels in children. An ongoing study in New York City has been following a birth cohort of 249 children whose mothers were assessed for PAH exposure with personal air monitors during their third trimester. By the age of 3, the children whose mothers had median or higher levels of PAH exposure showed developmental delay.55 By the age of 5, these same children showed full scale IQ and verbal IQ levels that were significantly lower than children with lower prenatal PAH exposure (P= 0.009).56 A similarly designed study in Krakow, Poland, also measured mothers' PAH exposure and found similar IQ point loss in the 5-year-old children who had greater prenatal PAH exposure.57 The researchers who followed the cohort in New York later published their estimate of the economic effects on these 249 children based on their lifetime earning if a modest reduction in PAH could be achieved. Their published finding proposed that a mere 0.25 ng/m3 reduction of PAHs, achievable by good indoor air purification, would boost the lifetime earnings of the cohort by $215 million.58
 
A number of convincing studies have also been published revealing the association between vehicular exhaust and both rates and severity of autism. Children who were gestationally exposed to high levels of vehicular exhaust were twice as likely to be autistic as those who had lower exposures, while those with higher exposure during the first year of life had triple the risk.59 The closer the mothers-to-be lived to a freeway, the higher the risk for having an autistic child.60 Subsequent studies have found that exposure to vehicular exhaust during the first and second trimesters do not increase the risk, but exposure during the third trimester does.61,62 Diesel exhaust turned out to be the greatest exhaust-source risk for the development of autism in the Children of Nurses’ Health Study II.63
 
The effect of PM on cognition in adults was the focus of a study that involved the 19,409 women in the Nurses’ Health Study Cognitive Cohort. These women ranged in age from 70 to 81 years, and their cognitive measurements were correlated with PM (both PM10 and PM2.5) levels.64 They found that women who were exposed to higher levels of both PM10 and PM2.5 for 7 to 14 years had significantly faster cognitive decline as they aged. The researchers were actually able to quantify the cognitive decline in relation to the levels of PM, showing that an increase of 10 µg/m3 of long-term PM 2.5 exposure resulted in the same reduction in cognition as would occur from 2 years of aging in those between the ages of 70 and 81 years. A similar result was reported by a group of researchers who used data from the US Department of Veterans Affairs Normative Aging Study.65 This group of males with an average age of 71 years had been administered cognitive testing 7 times during an 11-year period while levels of black carbon were used as a marker for vehicular exhaust. The researchers reported that for every doubling of the ambient levels of black carbon, the participants experienced a cognitive decline that was equivalent to 1.9 years of aging. In addition to cognitive decline, 2 studies have now clearly linked urban air pollution to increased risk of depression.66,67

Endocrine Effects

Urban air pollution has been linked to increased risk of infertility, obesity, and diabetes, all common problems in the modern population. Italian traffic policemen who were exposed daily to vehicular exhaust throughout their shifts had significantly lower levels of free testosterone than police assigned to other duties.68 Exposure to vehicular exhaust and cigarette smoke are also strongly associated with multiple sperm abnormalities associated with male infertility.69-71 Similarly, exposure to vehicular exhaust is also associated with increased female infertility rates.72 In infertile couples who have chosen to undergo in vitro fertilization, PM exposure during the preconception period also greatly increases risk of pregnancy loss.73
 
Children exposed to higher levels of vehicular air pollutants were up to 3 times more likely to develop type 1 diabetes than children breathing air with lower levels of vehicular exhaust compounds.74 In this study, the highest diabetes risk came from exposure to high levels of ozone derived from traffic sources. In a group of almost 400 German 10-year-olds, exposure to vehicular exhaust increased their incidence of insulin resistance, one of the first steps to developing type 2 diabetes.75 Long-term exposure to vehicular PM has also been directly associated with higher risk in adults for developing both metabolic syndrome and type 2 diabetes.76,77 Exposure to high levels of PM2.5 during the second trimester of pregnancy gave women a far higher risk of developing impaired glucose tolerance during pregnancy.78 Women with the highest PM2.5 exposure levels and with the closest proximity of heavy traffic were 2.6 times more likely to have problems with their blood sugar levels, although no direct link was found between vehicular exhaust and the risk of overt gestational diabetes mellitus. 
 
As mentioned above, PM from vehicular exhaust is known to lead to increased risk of the development of metabolic syndrome, one of whose manifestations is increased body weight. PAHs from urban air and from environmental tobacco smoke (ETS) are both associated with hugely increased risk levels for childhood obesity. Using data from the 2003-2008 National Health and Nutrition Examination Survey, researchers found that children in the second, third, and fourth quintiles of urinary PAH metabolites had risk factors for obesity that were 4.51, 2.57, and 8.09 times greater, respectively, than those in the lowest quintile.79 For the children exposed to both the higher PAH levels and ETS, the levels went up even higher, showing a clear synergistic effect leading to far greater body mass index in these children. 

Conclusion

Air is vital for human life, with the average adult inhaling more than 17,000 times every day. Unfortunately, with very few exceptions, each of those daily breaths may come with a substantial number of toxicants with severe health consequences. In fact, adverse health effects of air pollutants include cardiovascular disease, which is the most common cause of death in North America. These same air pollutants are associated with a variety of adverse respiratory, neurological, hormonal, and cognitive effects; they also increase a woman’s risk of having an autistic child. Much more focus needs to be placed on recognizing the important role that common air pollutants hold in health, with commensurate actions being taken to reduce the levels of common air pollutants in the home—the one environment most people are in control of. It is quite possible that one of the most effective preventive medicine modalities would be the installation of a high-quality air purifier in the home. 

About the Author

Walter J Crinnion, ND, has specialized in environmental medicine for the last 35 years. He currently provides a monthly podcast, CrinnionOpinion, to keep practitioners current in environmental medicine and has a 12-month training program for those who wish to gain expertise in this field. He and Joe Pizzorno, ND have co-authored the textbook Clinical Environmental Medicine that Elsevier is set to release in June 2018.

References

  1. World Health Organization. The top 10 causes of death. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed August 31, 2015.   
  2. World Health Organization. Ambient (outdoor) air quality and health. Available at: http://www.who.int/mediacentre/factsheets/fs313/en/. Accessed August 31, 2015.  
  3. US Environmental Protection Agency. 40th anniversary of the Clear Air Act. Available at: http://www.epa.gov/air/caa/40th.html. Accessed August 31, 2015.
  4. US Environmental Protection Agency. What are the six common air pollutants? Available at: http://www.epa.gov/airquality/urbanair/. Accessed August 31, 2015.  
  5. United Nations Environmental Programme. Pollutants: Particulate matter (PM). Available at: http://www.unep.org/tnt-unep/toolkit/pollutants/facts.html. Accessed August 31, 2015.
  6. Mazaheri M, Clifford S, Jayaratne R, et al. School children's personal exposure to ultrafine particles in the urban environment. Environ Sci Technol. 2014;48(1):113-120. 
  7. Kumar S, Verma MK, Srivastava AK. Ultrafine particles in urban ambient air and their health perspectives. Rev Environ Health. 2013;28(2-3):117-128. 
  8. Fukagawa NK, Li M, Poynter ME, et al. Soy biodiesel and petrodiesel emissions differ in size, chemical composition and stimulation of inflammatory responses in cells and animals. Environ Sci Technol. 2013;47(21):12496-12504. 
  9. Oberdorster G, Sharp Z, Atudorel V, et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A. 2002;65(20):1531-1543.
  10. Oberdorster G, Sharp Z, Atudorel V, et al. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol. 2004;16(6-7):437-445.
  11. Takenaka S, Karg E, Roth C, et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect. 2001;109 (Suppl 4):547-551.
  12. Semmler M, Seitz J, Erbe R, et al. Long-term clearance kinetics of inhaled ultrafine insoluble iridium particles from the rat lung, including transient translocation into secondary organs. Inhal Toxicol. 2004;16(6-7):453-459.
  13. Oh SM, Kim HR, Park YJ, Lee SY, Chung KH. Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BEAS-2B cells). Mutat Res. 2011;723(2):142-151.
  14. Frikke-Schmidt H, Roursgaard M, Lykkesfeldt J, Loft S, Nøjgaard JK, Møller P. Effect of vitamin C and iron chelation on diesel exhaust particle and carbon black induced oxidative damage and cell adhesion molecule expression in human endothelial cells. Toxicol Lett. 2011;203(3):181-189.
  15. Harrison CM, Pompilius M, Pinkerton KE, Ballinger SW. Mitochondrial oxidative stress significantly influences atherogenic risk and cytokine-induced oxidant production. Environ Health Perspect. 2011;119(5):676-681.
  16. Zhang P, Dong G, Sun B, et al. Long-term exposure to ambient air pollution and mortality due to cardiovascular disease and cerebrovascular disease in Shenyang, China. PLoS One. 2011;6(6):e20827.
  17. Ito K, Mathes R, Ross Z, Nadas A, Thurston G, Matte T. Fine particulate matter constituents associated with cardiovascular hospitalizations and mortality in New York City. Environ Health Perspect. 2011;119(4):467-473.
  18. Guaita R, Pichiule M, Maté T, Linares C, Díaz J. Short-term impact of particulate matter (PM(2.5)) on respiratory mortality in Madrid. Int J Environ Health Res. 2011;21(4):260-274.
  19. Katanoda K, Sobue T, Satoh H, et al. An association between long-term exposure to ambient air pollution and mortality from lung cancer and respiratory diseases in Japan. J Epidemiol. 2011;21(2):132-143.
  20. Yu JZ, Huang XH, Ho SS, Bian Q. Nonpolar organic compounds in fine particles: quantification by thermal desorption-GC/MS and evidence for their significant oxidatioin in ambient aerosols in Hong Kong. Anal Bioanal Chem. 2011;401(10):3125-3139.
  21. Agency for Toxic Substances and Disease Registry. Public Health Statement for Polycyclic Aromatic Hydrocarbons (PAHs). Available at: http://www.atsdr.cdc.gov/PHS/PHS.asp?id=120&tid=25. Accessed August 31, 2015.  
  22. Alexandrov K, Rojas M, Satarug S. The critical DNA damage by benzo(a)pyrene in lung tissues of smokers and approaches to preventing its formation. Toxicol Lett. 2010;198(1):63-68.
  23. Armstrong B, Hutchinson E, Unwin J, Fletcher T. Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: a review and meta-analysis. Environ Health Perspect. 2004;112(9):970-978.
  24. Xia T, Kovochich M, Nel AE. Impairment of mitochondrial function by particulate matter (PM) and their toxic components: implications for PM-induced cardiovascular and lung disease. Front Biosci. 2007 Jan 1;12:1238-1246.
  25. Jiang Y, Zhou X, Chen X, et al. Benzo(a)pyrene-induced mitochondrial dysfunction and cell death in p53-null Hep3B cells. Mutat Res. 2011;726(1):75-83.
  26. Shimada T, Gillam EM, Oda Y, et al. Metabolism of benzo(a)pyrene to trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene by recombinant human cytochrome P450 1B1 and purified liver epoxide hydrolase. Chem Res Toxicol. 1999;12(7):623-629.
  27. US Geological Survey. Volatile organic compounds (VOCs). Available at: http://toxics.usgs.gov/definitions/vocs.html. Accessed August 31, 2015.  
  28. Bolden AL, Kwiatkowski CF, Colborn T. New look at BTEX: Are ambient levels a problem? Environ Sci Technol. 2015;49(9):5261-5276. Epub 2015 Apr 15. 
  29. Woodruff TJ, Axelrad DA, Caldwell J, Morello-Frosch R, Rosenbaum A. Public health implications of the 1990 toxics concentrations across the United States. Environ Health Perspect. 1998;106(5):245-251.
  30. Pratt GC, Palmer K, Wu CY, Oliaei F, Hollerbach C, Fenske MJ. An assessment of air toxics in Minnesota. Environ Health Perspect. 2000;108(9):815-825.
  31. Edgar RT, Fenyves EJ, Rea WJ. Air pollution analysis used in operating an environmental control unit. Ann Allergy. 1979;42(3):166-173.
  32. Bergamaschi E, Burstolin A, De Palma G, et al. Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons. Toxicol Lett. 1999;108(2-3):241-247.
  33. Peters A, Skorkovsky J, Kotesovec F, et al. Associations between mortality and air pollution in central Europe. Environ Health Perspect. 2000;108(4):283-287. 
  34. Mar TF, Norris GA, Koenig JQ, Larson TV. Associations between air pollution and mortality in Phoenix, 1995-1997. Environ Health Perspect. 2000;108(4):347-353. 
  35. Apte JS, Marshall JD, Cohen AJ, Brauer M. Addressing global mortality from ambient PM2.5. Environ Sci Technol. 2015;49(13):8057-8066. Epub 2015 Jun 16. 
  36. Peters A, von Klot S, Heier M, et al; Cooperative Health Research in the Region of Augsburg Study Group. Exposure to traffic and the onset of myocardial infarction. N Engl J Med. 2004;351(17):1721-1730. 
  37. Brook RD, Rajagopalan S, Pope CA 3rd, et al; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378. 
  38. Lorenz M, Markus H, Bots M, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness. A systematic review and meta-analysis. Circulation. 2007;115(4):459-467. 
  39. Adar SD, Sheppard L, Vedal S, et al. Fine particulate air pollution and the progression of carotid intima-medial thickness: a prospective cohort study from the multi-ethnic study of atherosclerosis and air pollution. PLoS Med. 2013;10(4):e1001430. 
  40. Künzli N, Jerrett M, Garcia-Esteban R, et al. Ambient air pollution and the progression of atherosclerosis in adults. PLoS One. 2010;5(2):e9096. 
  41. Brucker N, Moro AM, Charão MF, et al. Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers. Sci Total Environ. 2013;463-464:884-893.
  42. Brucker N, Charão MF, Moro AM, et al. Atherosclerotic process in taxi drivers occupationally exposed to air pollution and co-morbidities. Environ Res. 2014 May;131:31-38. 
  43. Wong MC, Tam WW, Wang HH, et al. Exposure to air pollutants and mortality in hypertensive patients according to demography: a 10 year case-crossover study. Environ Pollut. 2014 Sep;192:179-185.
  44. Chen SY, Wu CF, Lee JH, et al. Associations between long-term air pollutant exposures and blood pressure in elderly residents of Taipei City: a cross-sectional study. Environ Health Perspect. 2015;123(8):779-784. Epub 2015 Mar 20. 
  45. Dong GH, Wang J, Zeng XW, et al. Interactions between air pollution and obesity on blood pressure and hypertension in Chinese children. Epidemiology. 2015;26(5):740-747.
  46. Qin XD, Qian Z, Vaughn MG, et al. Gender-specific differences of interaction between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study. Sci Total Environ. 2015 Oct 1;529:243-248.
  47. Hicken MT, Dvonch JT, Schulz AJ, Mentz G, Max P. Fine particulate matter air pollution and blood pressure: the modifying role of psychosocial stress. Environ Res. 2014 Aug;133:195-203. 
  48. Dong GH, Qian ZM, Trevathan E, et al. Air pollution associated hypertension and increased blood pressure may be reduced by breastfeeding in Chinese children: the Seven Northeastern Cities Chinese Children’s Study. Int J Cardiol. 2014;176(3):956-961. 
  49. Zhong J, Urch B, Speck M, et al. Endotoxin and ?-1,3-d-glucan in concentrated ambient particles induce rapid increase in blood pressure in controlled human exposures. Hypertension. 2015;66(3):509-516. Epub 2015 Jun 29.
  50. Burroughs Peña M, Romero KM, Velazquez EJ, et al. Relationship between daily exposure to biomass fuel smoke and blood pressure in high-altitude Peru. Hypertension. 2015;65(5):1134-1140. 
  51. Ciccone G, Forastiere F, Agabiti N, et al. Road traffic and adverse respiratory effects in children. SIDRIA Collaborative Group. Occup Environ Med. 1998;55(11):771-778. 
  52. Cook AG, deVos AJ, Pereira G, Jardine A, Weinstein P. Use of a total traffic count metric to investigate the impact of roadways on asthma severity: a case-control study. Environ Health. 2011 Jun 2;10:52. 
  53. Li S, Batterman S, Wasilevich E, Elasaad H, Wahl R, Mukherjee B. Asthma exacerbation and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan. Environ Health. 2011 Apr 23;10:34. 
  54. Macintyre EA, Gehring U, Mölter A, et al. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project. Environ Health Perspect. 2013;122(1):107-113. 
  55. Perera F, Rauh V, Whyatt RM, et al. Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environ Health Perspect. 2006;114(8):1287-1292. 
  56. Perera FP, Li Z, Whyatt R, et al. Prenatal airborne polycyclic aromatic hydrocarbon exposure and child IQ at age 5 years. Pediatrics. 2009;124(2):e195-202. 
  57. Edwards SC, Jedrychowski W, Butscher M, et al. Prenatal exposure to airborne polycyclic aromatic hydrocarbons and children’s intelligence at 5 years of age in a prospective cohort study in Poland. Environ Health Perspect. 2010;118(9):1326-1331. 
  58. Perera F, Weiland K, Neidell M, Wang S. Prenatal exposure to airborne polycyclic aromatic hydrocarbons and IQ: Estimated benefit of pollution reduction. J Public Health Policy. 2014;35(3):327-336. 
  59. Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013;70(1):71-77. 
  60. Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect. 2011;119(6):873-877. 
  61. Kalkbrenner AE, Windham GC, Serre ML, et al. Particulate matter exposure, prenatal and postnatal windows of susceptibility, and autism spectrum disorders. Epidemiology. 2015;26(1):30-42.
  62. Raz R, Roberts AL, Lyall K, et al. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case-control analysis within the Nurses’ Health Study II Cohort. Environ Health Perspect. 2015;123(3):264-270.
  63. Roberts AL, Lyall K, Hart JE, et al. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environ Health Perspect. 2013;121(8):978-984. 
  64. Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F. Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med. 2012;172(3):219-227. 
  65. Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Spiro A 3rd, Schwartz J. Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect. 2011;119(5):682-687. 
  66. Cho J, Choi YJ, Suh M, et al. Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma. J Affect Disord. 2014 Mar;157:45-51.
  67. Lim YH, Kim H, Kim JH, Bae S, Park HY, Hong YC. Air pollution and symptoms of depression in elderly adults. Environ Health Perspect. 2012;120(7):1023-1028. 
  68. Sancini A, Tomei F, Tomei G, et al. Exposure to urban stressors and free testosterone plasma values. Int Arch Occup Environ Health. 2011;84(6):609-616. 
  69. Rengaraj D, Kwon WS, Pang MG. Effects of motor vehicle exhaust on male reproductive function and associated proteins. J Proteome Res. 2015;14(1):22-37. 
  70. Richthoff J, Elzanaty S, Rylander L, Hagmar L, Giwercman A. Association between tobacco exposure and reproductive parameters in adolescent males. Int J Androl. 2008;31(1):31-39. 
  71. Rubes J, Selevan SG, Evenson DP, et al. Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality. Hum Reprod. 2005;20(10):2776-2783.
  72. Nieuwenhuijsen MJ, Basagaña X, Dadvand P, et al. Air pollution and human fertility rates. Environ Int. 2014 Sep;70:9-14.
  73. Perin PM, Maluf M, Czeresnia CE, Januário DA, Saldiva PH. Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET). J Assist Reprod Genet. 2010;27(7):371-382.
  74. Hathout EH, Beeson WL, Ischander M, Rao R, Mace JW. Air pollution and type 1 diabetes in children. Pediatr Diabetes. 2006;7(2):81-87.
  75. Thiering E, Cyrys J, Kratzsch J, et al. Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts. Diabetologia. 2013;56(8):1696-1704.
  76. Eze IC, Schaffner E, Foraster M, et al. Long-term exposure to ambient air pollution and metabolic syndrome in adults. PLoS One. 2015;10(6):e0130337.
  77. Weinmayr G, Hennig F, Fuks K, et al; Heinz Nixdorf Recall Investigator Group. Long-term exposure to fine particulate matter and incidence of type 2 diabetes mellitus in a cohort study: effects of total and traffic-specific air pollution. Environ Health. 2015 Jun 19;141:53.
  78. Fleisch A, Gould D, Rifas-Shiman S, et al. Air pollution exposure and abnormal glucose tolerance during pregnancy: the project viva cohort. Environ Health Perspect. 2014;122(4):378-383. 
  79. Kim HW, Kam S, Lee DH. Synergistic interaction between polycyclic aromatic hydrocarbons and environmental tobacco smoke on the risk of obesity in children and adolescents: The U.S. National Health and Nutrition Examination Survey 2003-2008. Environ Res. 2014 Nov;135:354-360.