Polycyclic aromatic hydrocarbons (PAHs) are organic compounds with two or more benzene rings (Meador 2010). This group includes about 100 compounds (Neff, 1979). However, thousands of variants are possible when other chemical groups are attached or when a carbon atom is replaced with nitrogen, sulfur or oxygen atoms (Pereira et al. 2009). PAHs are formed during the incomplete combustion of organic matter and fossil fuels (Environmental Canada 1994, Meador 2010).
Humans can be exposed to PAHs through different routes that include ingestion of contaminated food, dermal absorption (Suzuki and Yoshinaga 2007, Varlet et al. 2007, Li et al. 2008), and inhalation of contaminated particles (Environmental Canada 1994). Cigarette smoke has been shown to be an important source of exposure to PAHs in smokers. The concentration of benzo[a]pyrene can range from 0.5 to 7.8 µg/100 cigarette (Environmental Canada 1994). Traditionally, the major concern associated with PAH exposure to humans is carcinogenicity (Baars 2002, Laffon et al. 2006). However, adverse effects on human health can also include non-carcinogenic effects (Burstyn et al. 2005, Xu et al. 2010). In animals, it has been demonstrated that PAHs are able to alter endocrine function (Gentes et al. 2007), suppress the immune system (Trust et al. 1994, Kaminski et al. 2008), cause hemolytic anemia (Troisi et al. 2007), initiate the development of atherosclerotic plaque (Penn and Snyder 1988), elevate blood pressure (Sasser et al.1989), among other pathologies.
Evidence of cardiovascular disease has been documented in humans exposed to PAHs (Burstyn et al. 2005, Everett et al. 2010, Xu et al. 2010). In particular, elevated risk of cardiovascular disease has been demonstrated in occupational exposure to PAHs (revised by Burstyn et al. 2005), resulting in an increased risk of death from complications related to cardiovascular disease (Evanoff et al 1993).Studies investigating employees involved in asphalt paving demonstrated that exposure to benzo[a]pyrene and other PAHs is associated with fatal ischemic heart disease in an exposure-response relationship.The highest relative risk for fatal ischemic heart disease was observed with benzo[a]pyrene exposures of 273 ng/m3 or higher (Burstyn et al. 2005).
The biological mechanisms of cardiovascular disease associated to PAHs exposure are unclear. However, studies suggest that the mechanism involved in the pathogenesis and development of atherosclerotic plaques are similar or associated with the mechanisms involved in the carcinogenic and mutagenic properties of PAHs (Benditt and Benditt 1973, Albert et al. 1977,). It has been demonstrated that atherosclerotic plaques tend to be monoclonal, suggesting that mutation may be the mechanism for plaque development (Benditt and Benditt 1973). However, some uncertainties related to this possible mechanism remain, once it was verified that mosaic phenotypes in arteries as a consequence of injuries could also result in monoclonal atherosclerotic plaques, without involvement of somatic mutation by PAHs (Benditt and Benditt 1973, Murry et al. 1997).
Additionally, evidence suggests that oxidative stress could also result in the development of cardiovascular disease by causing inflammation, which has been recognized as an important factor in the development of atherosclerosis and cardiovascular disease (Kunzli and Tager 2005, Ridker 2009). Increased levels of inflammatory biomarkers are recognized as important predictors of cardiovascular disease, independent of smoking habits and previous incidence of cardiovascular disease (Danesh et al. 2000, Curb et al. 2003). More specifically, the C-reactive protein is the most studied of inflammatory biomarkers and its ability to predict cardiovascular disease has been confirmed. However, C-reactive protein levels are also associated with diabetes, hypertension, and obesity (Ridker, 2009). Everett et al. (2010) demonstrated that biomarkers of exposure to PAHs in humans were significantly associated with inflammatory biomarkers, indicating that oxidative stress resulting from exposure to PAHs could be a possible mechanism of cardiovascular disease in humans. The urinary PAH biomarker 2-hydroxyphenanthrene at concentration above 148 ng/g creatinine had an odds ratio of 3.17 for elevated cardiovascular disease when compared to urinary concentration below 48 ng/g creatinine. On the other hand, Clark III et al. (2012) did not observe a relationship between exposure to PAHs and biomarkers of cardiovascular disease, such as fibrinogen, homocysteine, and white blood cell count. Both papers analyzed a large scale population sample, and they also adjusted the models for age, race/ethnicity, body mass, and smoking habit. Everett et al. (2010) adjusted the models for presence of diabetes, blood pressure and physical activities. Variables such as age, body mass, smoking habits, blood pressure, etc. can increase the uncertainty of either the biomarker or the exposure to PAHs. This could directly influence the incidence of cardiovascular disease or result in a predisposition to cardiovascular disease unrelated to exposure to PAHs. The difference in results between these studies might be due to differences in the biomarkers that were chosen in each study.
In the United States it has been observed that urinary metabolites of PAHs were significantly associated with self-reported cardiovascular disease for two of the eight PAH metabolites studied (Xu et al. 2010). This research adjusted the results for potential confounding factors, which included demographic characteristics, smoking habit, alcohol consumption, blood pressure, plasma cholesterol, and high-density lipoprotein (HDL). However, diet, exercise activities, and genetic characteristics, which are known predisposing factors for cardiovascular disease were not included in the study. Another important limitation in this study was that the PAH metabolites analyzed were urinary monohydroxy because these metabolites reflect recent exposure to PAHs and might not be representative of chronic exposure scenarios that are of greatest interest. In addition, the urinary metabolites better represent PAHs congeners with 2-3 rings that are mainly excreted in the urine, while that more potent PAHs with four or more rings are excreted primarily in feces and might not be accurately considered (Ramesh et al. 2004 cited by Everett al. 2010). Xu et al. (2010) observed that different exposure categories, such as age, had a significant effect on the estimated risk of exposure, however, cross-sectional assumptions for different exposure categories is very limited.
According to the class materials and the information provided above, cardiovascular disease resulting from exposure to PAHs should be considered a risk to human health. Exposure to PAHs has the probability to cause significant injury (cardiovascular disease as mentioned), as well as the potential severity can include death. It was stated in class that to be considered a risk, there must be an identified source of hazard, a receptor, and an exposure pathway. PAHs are widespread contaminants with environmental concentrations that are greater in industrialized centres with large population sizes (Environment Canada, 2007). Moreover, it has been observed by Everett et al. (2010) that 16.2% of the sampled US population showed elevated concentrations of PAH metabolites in urine, indicative of elevated levels of exposure to the population.
In conclusion, it has been demonstrated in numerous studies that there is a significant correlation between exposure to PAHs and incidence of cardiovascular disease in humans. However, there are still numerous deficiencies in our understanding of this disease that must be identified in order to accurately characterize and quantify the risk of exposure to PAHs in humans. There is currently limited information on the potential of PAHs to cause cardiovascular disease in low dose exposure. There is limited information on the association of background exposure to PAHs and cardiovascular disease. As mentioned in class, if the mechanism of cardiovascular disease development involves damage to the DNA, as a carcinogenic process, it could not be considered background, since any level of exposure could theoretically cause damage and result in disease. It is necessary to conduct additional studies to better understand the effects and risk of chronic exposure to PAHs in people, such as occupational exposure over a lifetime. Moreover, it would be of significant value to determine the potency of PAHs with a greater number of rings to cause incidence of cardiovascular disease. It would also be important to determine if an increased exposure to PAHs results in an increased risk of other inflammatory diseases and vice-versa.
- Albert RE, Vanderlaan M, Burns FJ, Nishizumi M (1977) Effect of carcinogens on chicken atherosclerosis. Cancer Research, 37:2232–2235.
- Baars BJ (2002) The wreckage of the oil tanker “Erika” – human health risk assessment of beach cleaning, sunbathing and swimming. Toxicology Letters 128:55-68
- Benditt EP, Benditt JM (1973). Evidence for a monoclonal origin of human atherosclerotic plaques. Proceedings of National Academy of Science of the United States of America,70:1753-1756
- Burstyn I, Kromhout H, Partanen T, Svene O, Langard S, Ahrens W, Kauppinen T, Stucker I, Shaham J, Heederik D,Ferro G, Heikkila P, Hooiveld M, Johansen C, Radem BG, Boffetta P (2005). Polycyclic Aromatic Hydrocarbons and Fatal Ischemic Heart Disease. Epidemiology, 16 (6):744-750
- Clark III JD, Serdar B, Lee DJ, Arheart K, Wilkinson JD, Fleming LE (2012). Exposure to polycyclic aromatic hydrocarbons and serum inflammatory markers of cardiovascular disease. Environmental Research, 117:132–137
- Curb, J.D., Abbott, R.D., Rodriguez, B.L., Sakkinen, P., Popper, J.S., Yano, K., Tracy, R.P. (2003). C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 107:2016–2020
- Danesh, J., Whincup, P., Walker, M., Lennon, L., Thomson, A., Appleby, P., Gallimore, J.R., Pepys, M.B. (2000) Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ, 321(7255):199–204.
- Environment Canada (1994) Canadian environmental protect act – Priority substances list assessment report: Polycyclic aromatic hydrocarbons. In: Services MoSa (ed), Ottawa, Ontario
- Environment Canada (2007) Environment Canada .Ambient air measurements of polycyclicaromatichydro-carbons (PAH), polychlorinateddibenzo-p-dioxins(PCDD) and polychlorinated dibenzofuransin. Canada (1987–1997). Environmental Technology Center Report, 2007.
- Evanoff BA, Gustavsson P, Hogstedt C (1993) Mortality and incidence of cancer in a cohort of Swedish chimney sweeps: an extended follow up study. British Journal of Industry Medicine 50:450-459
- Everett CJ, King DE, Player MS, Matheson EM, Post RE, Mainous III AG (2010). Association of urinary polycyclic aromatic hydrocarbons and serum C-reactive protein. Environmental Research, 110:79–82.
- Gentes M-L, McNabb A, Waldner C, Smits JEG (2007) Increased thyroid hormone levels in tree swallows (Tachycineta bicolor) on reclaimed wetlands of the Athabasca oil sands. Archives of Environmental Contamination and Toxicology 53:287-292
- Kaminski NE, Kaplan BLF, Holapple MP (2008) Toxic responses of the immune system. In: Klaassen CD (ed) Casarett and Doull’s Toxicology – The Basic Science of Poisons.
- Kunzli and Tager, 2005 Kunzli N, Tager IB (2005) Air pollution: from lung to heart. Swiss Med Wkly, 135:697–702.
- Laffon B, Fraga-Iriso R, Pérez-Cadahía B, Méndez J (2006) Genotoxicity associated to exposure to Prestige oil during autopsies and cleaning of oil-contaminated birds. Food and Chemical Toxicology 44:1714-1723
- Li et al., 2008 Li Z, Sandau CD, Romanoff LC, Caudill SP, Sjodin A, Needham LL (2008) Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population. Environ Research, 107:320–31.
- Meador JP (2010) Ecotoxicology: a derivative of encyclopedia of ecology. In: Jorgensen SE, Fath BD (eds) Ecotoxicology: a derivative of encyclopedia of ecology. Elsevier, San Diego, California
- Murry CE, Gipaya CT, Bartosek T (1997) Monoclonality of smooth muscle cells in human atherosclerosis. The American Journal of Pathology, 151:697-705
- Neff J M (1979) Polycyclic aromatic hydrocarbons in the aquatic environment: sources, fates, and biological effects. Applied Science, London.
- Penn A, Snyder C. (1988) Arteriosclerotic plaque development is ‘promoted’ by polynuclear aromatic hydrocarbons. Carcinogenesis, 9:2185-2189
- Pereira MG, Walker LA, Wright J, Best J, Shore RF (2009) Concentrations of Polycyclic Aromatic Hydrocarbons (PAHs) in the Eggs of Predatory Birds in Britain. Environmental Science and Technology 43:9010-9015
- Ridker, P.M. (2009) C-reactive protein: eighty years from discovery to emergence as a major risk marker for cardiovascular disease. Clinical Chemistry 55(2):209–215.
- Sasser LB, Lundstrom DL, Zangar RC (1989). Elevated blood pressure and heart rate in rats exposed to a coal-derived complex organic mixture. Journal of Applied Toxicology, 9:47-52.
- Suzuki K, Yoshinaga J (2007) Inhalation and dietary exposure to polycyclic aromatic hydrocarbons and urinary 1-hydroxypyrene in non-smoking university students. International Archives of Occupational Environmental Health, 81:115–21.
- Troisi G, Borjesson L, Bexton S, Robinson I (2007) Biomarkers of polycyclic aromatic hydrocarbon (PAH)-associated hemolytic anemia in oiled wildlife. Environmental Research, 105:324-329
- Trust KA, Fairbrother A, Hooper MJ (1994) Effects of 7,12-dimethylbenz[a]anthracene on immune function and mixed-function oxygenase activity in the european starling. Environmental Toxicology and Chemistry, 13:821-830
- Varlet V, Serot T, Monteau F, Le Bizec B, Prost C (2007) Determination of PAH profiles by GC–MS/MS in salmon processed by four cold-smoking techniques. Food Additives and Contaminantes, 24:744–57.
- Xu X, Cook RL, Ilacqua VA, Kan H,Talbott EO, Kearney (2010). Studying associations between urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and cardiovascular diseases in the United States. Science of the Total Environment, 408:943–4948.