Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants generated primarily during the incomplete combustion of organic materials (e.g. coal, oil, petrol, and wood). Emissions from anthropogenic activities predominate (automobile emissions and cigarette smoke); nevertheless, some PAHs in the environment originate from natural sources (e.g. open burning, natural losses or seepage of petroleum or coal deposits, and volcanic activities).

Particulate Matter is generally categorised on the basis of the size of the particles that reflect their aerodynamic diameter (e.g PM2.5 refers to particles with an aerodynamic diameter of less than 2.5µm). PM is made up of a wide range of components and is formed from a variety of sources and processes. Ambient air levels of PM comprise primary particles emitted directly into the atmosphere from combustion sources and secondary particles formed by chemical reactions in the air. Ambient air PM is released from both anthropogenic and natural sources (such as sea spray, Saharan dust or volcanos). The most common anthropogenic sources are stationary fuel combustion and transport. Road transport gives rise to primary particles from engine emissions, as well as various non-exhaust emissions such as tire and brake wear. Secondary PM is formed from emissions of ammonia, sulphur dioxide and oxides of nitrogen as well as from emissions of organic compounds from both combustion sources and vegetation.

Substances included in the substance group, listed according to availability of toxicology and human biomarker data, in categories A, B and C substances are as follows:

Category A: NO₂, SO₂, O₃, CO

Category B: Acenaphthene, Acenaphthylene, Antracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(e)pyrene, Benzo(ghi)perylene, Benzo(j)fluoranthene, Benzo(k)fluoranthene, Dibenzo(ah)anthracene, Fluoranthene, Fluorene, Chrysene/Benzo(a)phenanthrene, Indeno(123-cd)pyrene, Naphthalene, Phenantrene, Pyrene, 1-Methylnapthalene, 1-Methylphenanthrene, 2,6-Dimethylnapthalene, 2-Methylnapthalene, 7.12-Dimethylbenz(a)anthracene, 2,3,5-trimethylnaphthalene, Benzene, Toluene, Ethylbenzene, Xylene, o-Xylene, m-Xylene, p-Xylene, Formaldehyde, Acetaldehyde

Category C: Biologicals (mould, pollen), Particulate matter (PM1), Ultra-fine particles (UFP)

Many PAHs are known or suspected carcinogenic and mutagenic compounds (e.g., benzo(a)pyrene, dibenzo(a,h) anthracene, etc.). They are included in the candidate list under article 59 of REACH which contains a number of complex substances derived from petroleum and coal such as: coal tar pitch, high temperature (CTPHT) – EC 266-028-2; anthracene oil EC 292-602-7 and other anthracene related fractions. The reasons for inclusion are the Persistent Bioaccumulative Toxic (PBT), very Persistent very Bioaccumulative (vPvB) and carcinogenic properties of the PAHs which are present as constituents in these UVCB substances (substances of Unknown or Variable composition, Complex reaction products or Biological materials, ECHA)

Currently eight PAH congeners (Benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), benzo[a]antracene (BaA), chrysene (CHR), benzo[b]fluoranthene, (BbF), benzo[j]fluoranthene (BjF), benzo[k]fluoranthene (BkF), dibenzo[a,h]antracene (DBAhA)) are classified as known carcinogens in Annex VI of Regulation (EC) 1272/2008 (Classification Labelling and Packaging, CLP regulation). These are legally classified carcinogens of Category 1B acc. to the CLP regulation.

Benzo[a]pyrene (BaP) and chrysene (CHR) are also legally classified mutagens (CLP Cat. 1B; CHR: CLP Cat. 2). In addition, BaP is a classified reprotoxicant (CLP: Cat. 1B). Lack of ‘CMR (Carcinogenic Mutagenic Reprotoxic)’ classification for the other PAH congeners may rather be attributed to the comparatively limited database available for these compounds. There are indications that the carcinogenic potency of some further PAH congeners, e.g. some of the dibenzopyrenes, may even be considerably higher than that of the lead compound BaP.

The mechanism of toxicity is considered to be interference with the function of cellular membranes as well as with enzyme systems which are associated with the membrane. It has been proven that PAHs can cause carcinogenic and mutagenic effects and are potent immune-suppressants. Effects have been documented on immune system development, humoral immunity and on host resistance (Armstrong, 2004; CCME, 2010) PAH-induced carcinogenesis can result when a PAH-DNA adduct forms at a site critical to the regulation of cell differentiation or growth. PAHs have been shown to exert endocrine and developmental toxicity in experimental animals, including decreased weight of reproductive organs, damage to growing ovarian follicles, decreased fertility, embryonic damage and lethality or developmental defects of testis and spermatogenesis in males (Borman, 2000; MacKenzie, 1981; Rigdon, 1964).

PAHs are highly lipid soluble and thus readily absorbed from the gastrointestinal tract of mammals. They are absorbed through ingestion, inhalation, and dermal contact, according to animal study data. The percentage absorbed varies in these studies for several reasons, including the vehicle (transport medium) in which the PAHs are found (Kawamura, 1988). In general, PAHs not bound to particulate matter may be absorbed in the lungs better than the same dose found on the surface of airborne particulate matter (Seto, 1993; Cresia, 1976). They are rapidly distributed in a wide variety of tissues with a marked tendency for localization in body fat. Metabolism of PAHs occurs via the cytochrome P450-mediated mixed function oxidase system with oxidation or hydroxylation as the first step. Because of their lipophilic nature, PAHs can accumulate in breast milk and adipose tissue. However, biliary and urinary excretion of PAHs is relatively efficient because of the wide distribution of enzymes that transform PAHs into polar metabolites.

PAHs are predominantly metabolized in the liver, via CYP enzymes (enzymes in the P-450 mixed-function oxidase system) (Monteith, 1987; Kapitulnik, 1977; Kiefer, 1988).

In addition to the liver and kidneys, metabolism of PAHs occurs in the adrenal glands, testes, thyroid, lungs, skin, sebaceous glands, and small intestines (ATSDR, 1995).

PAHs are transformed initially to epoxides, which are converted to dihydrodiol derivatives and phenols. Glucuronide and sulfate conjugates of these metabolites are excreted in the bile and urine. Glutathione conjugates are further metabolized to mercapturic acids in the kidney and are excreted in the urine.

The hydroxylated metabolites of the PAHs are excreted in human urine both as free hydroxylated metabolites and as hydroxylated metabolites conjugated to glucuronic acid and sulfate (CDC, 2005). A commonly measured urinary metabolite is 1-hydroxypyrene (Santella, 1993; Becher, 1983; Granella, 1993).

Metabolism is a prerequisite for hepatobiliary excretion and elimination through the feces, regardless of route of entry. Excretion half-lives in feces and urine have been reported in animal studies as 22 hours and 28 hours, respectively (Becher, 1983).

Exposure to PAHs is almost always to mixtures that pose a challenge in developing conclusions (Samet, 1995). Several epidemiologic studies have shown increased cancer mortality in workers exposed to PAHs.

Below, you will find a summary of the hazardous properties of CO, SO₂, O₃, NOx, particulate matter, benzene and VOCs. For more details including levels reported, please consult the scoping document on PAHs.

Carbon Monoxide is a colourless, odourless, tasteless gas that is slightly lighter than air. The main health effects related to exposure to CO are: headaches, dizziness, slows mental processes, and at high levels can lead to death. CO prevents the normal transport of oxygen by the blood. This can lead to a significant reduction in the supply of oxygen to the heart, particularly in people suffering from heart disease.

SO₂ is a colourless gas. It reacts on the surface of a variety of airborne solid particles, is soluble in water and can be oxidised within airborne water droplets. Even moderate concentrations may result in constriction of the lung airways. This effect is particularly likely to occur in people suffering from asthma and chronic lung disease. Tightness in the chest and coughing occur at high levels, and lung function of asthmatics may be impaired to the extent that medical help is required. Sulphur dioxide pollution is considered more harmful when particulate and other pollution concentrations are high.

NOx is a collective term used to refer to two species of oxides of nitrogen: nitric oxide (NO) and nitrogen dioxide (NO₂). The main health effects associated to exposure to NOx are: shortness of breath or coughing and enhanced risk of respiratory disease. NO₂ is associated with several respiratory adverse effects on human health. At high levels NO₂ causes inflammation of the airways. Long term exposure may affect lung function and respiratory symptoms. NO₂ also enhances the response to allergens in sensitive individuals. Nitrogen dioxide can irritate the lungs and lower resistance to respiratory infections such as influenza. Continued or frequent exposure to concentrations that are typically much higher than those normally found in the ambient air may cause increased incidence of acute respiratory illness in children.

O₃ is the tri-atomic form of molecular oxygen. It is a strong oxidising agent, and hence highly reactive. Exposure to high levels of O₃ may result in irritation to eyes and nose. Very high levels can damage airways leading to inflammatory responses. Ozone reduces lung function and increases incidence of respiratory symptoms, respiratory hospital admissions and mortality. Ground level ozone can also cause damage to many plant species leading to loss of yield and quality of crops, damage to forests and impacts on biodiversity.

Particulate matter is a complex mixture of organic and inorganic substances, present in the atmosphere as both liquids and solids. Coarse particulates can be regarded as those with an aerodynamic diameter greater than 2.5 µm (micrometres), and fine particles less than 2.5 µm. Both short-term and long-term exposure to ambient levels of PM are consistently associated with respiratory and cardiovascular illness and mortality as well as other adverse health effects. It is not currently possible to discern a threshold concentration below which there are no effects on public health. Fine particles are deposited in the lowest part of the human respiratory tract, where they can cause inflammation and a worsening of the condition of people with heart and lung diseases. In addition, they may carry surface-absorbed carcinogenic compounds into the lungs.

Benzene is a colourless, clear liquid compound. It is fairly stable but highly volatile, i.e. it readily evaporates. Benzene is a recognized human carcinogen that interacts with the genetic material and, as such, no absolutely safe level can be specified in ambient air. Studies in workers exposed to high levels have shown an excessive risk of leukemia.

Volatile organic compounds (VOCs) comprise a very wide range of individual substances, including hydrocarbons, halocarbons and oxygenates. All are organic compounds and of sufficient volatility to exist as vapour in the atmosphere. Methane is an important component of VOCs, its environmental impact principally related to its contribution to global warming and to the production of ozone in the troposphere. Regional effects derive from non-methane VOCs (NMVOCs), such as benzene and toluene.

BaP is a potent carcinogen. Possible chronic health effects include cancer, central nervous system disorders, liver and kidney damage, reproductive

The atmosphere is the most important means of PAH dispersal, it receives the bulk of the PAH environmental load resulting in PAHs being ubiquitous in the environment.

Exposure to PAHs is affected by proximity to intense combustion sources, such as heavily trafficked roads, municipal waste incinerators and industrial sites. An additional source of PAHs is combustion of solid fuel for space heating. In this regard, special attention ought to be paid to the use of biomass in large urban and metropolitan areas, which, if not controlled, may contribute substantially to the overall PAH exposure of the urban population. Biomass combustion for heating is expected to contribute to indoor exposure as well.

For the rest of air pollutants, the only relevant route of exposure is inhalation. In practice, people are exposed to various levels of air pollutants during their daily activity, depending on a) the levels of these pollutants in the various microenvironments and b) the inhalation rate which is related to age, gender and the respective activity performed in the microenvironment. The concentration levels of the pollutants are clearly linked to the proximity to major sources, e.g. proximity to heavily trafficked roads results in increased levels of traffic related pollutants such as PM, NOx and benzene, but not for VOCs like acetaldehyde and formaldehyde that are explicitly associated with indoor sources (Sarigiannis, 2011). In this case, the levels of exposure are associated with the presence of building materials and furniture containing the respective compounds and the air exchange levels of the respective microenvironment.

PAHs are also found in a multitude of consumer articles and mixtures. Although they are not produced intentionally for this purpose, they are present in these products due to the use of plasticisers (e.g. extender oils) or carbon black (soot) in the manufacture of rubber or other elastomers.

It is well-known that PAHs can be formed during the incomplete combustion of organic substances. PAHs are also found in petroleum products. On the other hand, it is not well-known that PAHs can be produced biologically. For example, they can be synthesized by certain plants and bacteria or formed during the degradation of vegetative matter.

From a technical point of view, methods already exist for the determination of some PAHs (such as BaP) in urine. Further methodological developments may be necessary however; solutions to this may be found by the European Human Biomonitoring Initiative cost-effectively. Considering that exposure to PAHs may occur from multiple sources and through multiple exposure routes, further understanding on the determination of the overall exposure levels is necessary. HBM information would be extremely useful in determining the overall exposure of the general population or of sensitive sub-populations, particularly children and specific target groups, to carcinogenic PAHs. HBM data would also help us determine whether the existing restrictions and limitations (in articles, in certain foods, in water, in ambient air) have a positive effect in reducing exposure to this ubiquitous family of chemicals or not. Finally, the HBM4EU work can also be very relevant in assessing worker exposure to these chemicals in certain activities (petrochemical plants, manufacture of anodes, etc.).

With regard to the air pollutants, actual biomarkers of exposure have been established only for benzene. These include either major benzene metabolites such as S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA). However, due to their low sensitivity in common environmental settings, unmetabolized urinary benzene has also been suggested as a low exposure sensitive biomarker (Fustinoni, 2005a and 2005b). With regard to other air pollutants, at the moment there are no well-established exposure biomarkers. Previous efforts have associated exposure to high levels of exposure to SO₂ with S-sulfonates in nasal lavage (Bechtold, 1993) and exhaled breath CO (Sandberg, 2011), while in the case of the main air pollutants exposure is usually associated with markers of inflammation (Dadvand, 2014).

Relevant individual PAHs to biomonitor, where feasible via their specific metabolites, include:

• 8 carcinogenic PAHs in entry 50 of Annex XVII to REACH: Benzo[a]pyrene, Benzo[e]pyrene, Benzo[a]anthracene, Chrysen, Benzo[b]fluoranthene, Benzo[j]fluoranthene, Benzo[k]fluoranthene and Dibenzo[a,h]anthracene
• 16 USEPA priority PAHs, included in numerous EN and national standards:

• • Naphthalene (CAS No. 91-20-3); Acenaphthene (CAS No.83-32-9); Acenaphthylene (CAS No.208-96-8); Fluorene (CAS No.86-73-7); Anthracene (CAS No.120-12-7); Phenanthrene (CAS No. 85-01-8); Fluoranthene (CAS No.206-44-0); Pyrene (CAS No.129-00-0); Benzo(a)anthracene (CAS No.56-55-3); Chrysene (CAS.No.218-01-9); Benzo(b)fluoranthene (CAS No. 205-99-2); Benzo(k)fluoranthene (CAS No.207-08-9); Benzo(a)pyrene (CAS No.50-32-8); Indeno(1,2,3-cd)pyrene (CAS No.193-39-5); Dibenzo(ah)anthracene (CAS No.53-70-3); Benzo(ghi)perylene (CAS No.191-24-2)

• Potentially also alkylated PAHs: 7,12-dimethylbenzo(a)anthracene; 1-methylphenanthrene; 2,3,5-trimethylnaphthalene; 1-methylnaphthalene; 2-methylnaphthalene and 2,6-dimethylnaphthalene.

To study the exposure to PAHs, urinary mono-hydroxylated PAHs (OH-PAHs), a group of PAH metabolites, are commonly used as biomarkers (39). Among the OH-PAHs, 1-hydroxypyrene (1-PYR) is the most commonly used PAH biomarker in both occupational as well as in the general population from various countries (40).

Following on the Advisory Board’s advice to strengthen the science-policy interface, HBM4EU developed a strategic and systematic approach to outreach and align science and policy. A legislative mapping exercise was done by RPA Consultants, providing relevant public policy processes that may benefit from the knowledge generated under HBM4EU. The documents are available for consultation here, with the tables presented here.

PAHs are regulated on the basis of the National Emission Ceilings Directive 2001/81/EC. Moreover, Regulation (EU) 1272/2013 on PAHs in articles for supply to the general public, amended entry 50 of Annex XVII to REACH. According to this regulation, the use of PAHs has been restricted by a limit of 1 mg/kg (0,0001 % by weight) of BaP and 10 mg/kg (0,001 % by weight) for each of 8 PAHs for extender oils used for the production of tires or parts of tires. This regulation entered into force in January 2010. In addition, subject to the detailed scope of the restriction, a limit of 1 mg/kg is established for the rubber and plastic parts of many types of consumer articles. In the case of toys and childcare articles the limit is lowered to 0.5 mg/kg for each of 8 carcinogenic PAHs. The restriction entered into force in December 2015.

Anthracene oil and coal tar pitch are included in the 6^th recommendation of the European Chemicals Agency, of 1 July 2015 for the inclusion of substances in Annex XIV to REACH.

The main policy instrument regarding air pollutants within the EU is the Ambient Air Quality Directive [26, 27] and the National Emission Ceilings (NEC) Directive [48]. In 2011-2013 the Commission conducted a review of the EU air policies which resulted in the adoption of the Clean Air Policy Package in which the EU proposed a Clean Air Programme for Europe, updating the 2005 Thematic Strategy on Air Pollution in order to set new objectives for EU air policy for 2020 and 2030.

The main legislative instrument towards 2030 objectives of the Clean Air Programme is Directive 2016/2284/EU on the reduction of national emissions of certain atmospheric pollutants which entered into force on 31 December 2016. This Directive sets national reduction commitments for the five pollutants (sulphur dioxide, nitrogen oxides, volatile organic compounds, ammonia and fine particulate matter) responsible for acidification, eutrophication and ground-level ozone pollution which leads to significant negative impacts on human health and the environment.

For more information, specific to each PAH substance, please consult the scoping document on PAHs, Table 1 on the legislative framework regarding PAHs and other air pollutants

1. What is the current exposure of the EU population to PAHs?
2. What is the current exposure of different occupational groups?
3. Does exposure differ between countries? Why?
4. Is there an association between air quality and human exposure to PAHs??
5. Can we see a decline in exposure to the eight PAHs restricted under REACH?
6. Can HBM4EU data inform the development of legislation specifically targeting exposure to PAHs through ambient air?

In the interest of transparency and accountability, HBM4EU invites interested stakeholders to submit comments on the scoping document.

All submitted comments will be made available for download on this webpage and will be taken into consideration by the HBM4EU consortium, where possible.

Please click here to submit your comments.

Please click here to access the Substance Report.

Armstrong, B., et al., Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis. Environmental Health Perspectives, 2004. 112(9): p. 970-978. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247189/

CCME, Canadian soil quality guidelines for potentially carcinogenic and other PAHs: scientific criteria document. 2010: Winnipeg. https://www.ccme.ca/files/Resources/supporting_scientific_documents/pah_soqg_scd_1445.pdf

Borman, S.M., et al., Ovotoxicity in female Fischer rats and B6 mice induced by low-dose exposure to three polycyclic aromatic hydrocarbons: comparison through calculation of an ovotoxic index. Toxicol Appl Pharmacol, 2000. 167(3): p. 191-8. https://www.sciencedirect.com/science/article/pii/S0041008X00990069

MacKenzie, K.M. and D.M. Angevine, Infertility in mice exposed in utero to benzo(a)pyrene. Biol Reprod, 1981. 24(1): p. 183-91. https://academic.oup.com/biolreprod/article/24/1/183/2766988

Rigdon, R.H. and E.G. Rennels, Effect of feeding benzpyrene on reproduction in the rat. Experientia, 1964. 20(4): p. 224-6 https://link.springer.com/article/10.1007/BF02135417

Kawamura, Y., et al., The effect of various foods on the intestinal absorption of benzo(a)pyrene in rats. Shokohin Eiseigaku Zasshi / Journal of the Food Hygienic Society of Japan, 1988. 29(1): p. 21-25. https://www.jstage.jst.go.jp/article/shokueishi1960/29/1/29_1_21/_article

Seto, H., et al., Determination of polycyclic aromatic hydrocarbons in the lung. Arch Environ Contam Toxicol, 1993. 24(4): p. 498-503. https://link.springer.com/article/10.1007/BF01146169

Creasia, D.A., J.K. Poggenburg, and P. Nettesheim, Elution of benzo[a]pyrene from carbon particles in the respiratory tract of mice. Journal of Toxicology and Environmental Health, 1976. 1(6): p. 967-975. https://www.osti.gov/biblio/6736150-effect-respiratory-infection-elution-benzo-pyrene-from-carbon-particles-respiratory-tract-mice

Monteith, D.K., et al., Metabolism of benzo[a]pyrene in primary cultures of human hepatocytes: dose-response over a four-log range. Carcinogenesis, 1987. 8(7): p. 983-8. https://academic.oup.com/carcin/article-abstract/8/7/983/2478337?redirectedFrom=fulltext

Kapitulnik, J., et al., Hydration of arene and alkene oxides by epoxide hydrase in human liver microsomes. Clin Pharmacol Ther, 1977. 21(2): p. 158-65. https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt1977212158

Kiefer, F., O. Cumpelik, and F.J. Wiebel, Metabolism and cytotoxicity of benzo(a)pyrene in the human lung tumour cell line NCI-H322. Xenobiotica, 1988. 18(6): p. 747-55. https://www.tandfonline.com/doi/abs/10.3109/00498258809041713

ATSDR, Agency for Toxic Substances and Disease Registry. Toxicological profile for polycyclic aromatic hydrocarbons (PAHs) (update). 1995, US Department of Health and Human Services: Atlanta. https://www.atsdr.cdc.gov/toxprofiles/tp69.pdf

CDC, Centers for Disease Control and Prevention. Third National Report on Human Exposure to Environmental Chemicals. 2005: Atlanta GA. https://www.jhsph.edu/research/centers-and-institutes/center-for-excellence-in-environmental-health-tracking/Third_Report.pdf

Santella, R.M., et al., Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers. Cancer Epidemiol Biomarkers Prev, 1993. 2(1): p. 59-62. http://cebp.aacrjournals.org/content/cebp/2/1/59.full.pdf

Becher, G. and A. Bjorseth, Determination of exposure to polycyclic aromatic hydrocarbons by analysis of human urine. Cancer Lett, 1983. 17(3): p. 301-11. https://www.sciencedirect.com/science/article/pii/0304383583901684

Granella, M. and E. Clonfero, Urinary excretion of 1-pyrenol in automotive repair workers. International Archives of Occupational and Environmental Health, 1993. 65(4): p. 241-245. https://link.springer.com/article/10.1007/BF00381197

Samet, J.M., What can we expect from epidemiologic studies of chemical mixtures? Toxicology, 1995. 105(2): p. 307-314. https://www.sciencedirect.com/science/article/pii/0300483X95032277

Sarigiannis, D.A., et al., Exposure to major volatile organic compounds and carbonyls in European indoor environments and associated health risk. Environment International, 2011. 37(4): p. 743-765. https://www.sciencedirect.com/science/article/pii/S0160412011000079

Fustinoni, S., et al., Monitoring low benzene exposure: Comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms. Cancer Epidemiology Biomarkers and Prevention, 2005a. 14(9): p. 2237-2244. http://cebp.aacrjournals.org/content/14/9/2237

Fustinoni, S., et al., Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure. Chemico-Biological Interactions, 2005b. 153-154: p. 253-256. https://www.sciencedirect.com/science/article/pii/S0009279705000943

Bechtold, W.E., et al., Biological markers of exposure to SO2: S-sulfonates in nasal lavage. J Expo Anal Environ Epidemiol, 1993. 3(4): p. 371-82.

Sandberg, A., et al., Carbon monoxide levels in exhaled breath as a measure of recent smoking status. The Clinical Respiratory Journal, 2011. 5: p. 8-9. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1752-699X.2011.00266_9.x

Dadvand, P., et al., Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients. Eur Respir J, 2014. 44(3): p. 603-13. https://erj.ersjournals.com/content/44/3/603