Biomonitoring Summary
Polycyclic Aromatic Hydrocarbons Overview
General Information
Polycyclic aromatic hydrocarbons (PAHs) are a class of more than 100 chemicals generally produced during the incomplete burning of organic materials, including coal, oil, gas, wood, garbage, and tobacco. PAHs are composed of up to six benzene rings fused together such that any two adjacent benzene rings share two carbon bonds. Examples include phenanthrenes, naphthalene, and pyrene. Important PAH sources include motor vehicle exhaust, residential and industrial heating sources, coal, crude oil and natural gas processing, waste incineration, and tobacco smoke. The emitted PAHs can form or bind to particles in the air, and particle size depends in part on the source of the PAHs. The smaller or fine particulates (e.g., PM2.5 or smaller) have higher concentrations of PAHs than the larger or coarse particulates (Bostrom et al., 2002; Rehwagen et al., 2005). Ambient air PAH concentrations show seasonal variation (IPCS, 1998; Rehwagen et al., 2005). Smoking, grilling, broiling, or other high temperature processing leads to PAH formation in meat and in other foods, as well. Uncooked foods and vegetables generally contain low levels of PAHs but can be contaminated by airborne particle deposition or growth in contaminated soil. With the exception of naphthalene, the PAHs described here are not produced commercially in the U.S.
Human exposure usually occurs to PAH mixtures rather than to individual chemicals, and PAH mixture composition varies with the combustion source and temperature (ATSDR, 1995). For persons without occupational exposure, important sources of PAHs include ambient air pollution (especially motor vehicle exhaust), smoke from wood or fossil fuels, tobacco smoke, and foods. PAH exposure can occur in workplaces where petroleum products are burned or coked, such as coke production, coal gasification and gas refining, iron or steel production, roofing tar and asphalt application, waste incineration, and aluminum smelting. Coal tar ointments containing PAHs are used to treat several inflammatory skin conditions.
PAHs are lipid soluble and can be absorbed through the skin, respiratory tract, and gastrointestinal tract. PAH metabolism is complex and occurs primarily in the liver, and to a lesser extent, in other tissues. PAH elimination occurs via urine and feces, and urinary metabolites are eliminated within a few days (Ramesh et al., 2004). PAHs and their urinary hydroxylated metabolites measured in at CDC are shown in the table. The metabolic pathways and enzyme-inducing effects of specific PAHs, such as benz[a]pyrene, have been actively studied to elucidate cancer potential and causal mechanisms (Ramesh et al., 2004). Although immunologic, kidney and brain toxicity have been seen in animals after high doses were administered, it is unclear if similar effects may occur in humans. Lung, bladder, and skin cancers have been reported in occupational settings following high PAH exposures (Bosetti et al., 2007; Bostrom et al., 2002; Lloyd, 1971). Exposure to fine particulates has been associated with fetal growth retardation, respiratory disorders, and cardiovascular disease, but it is unknown whether PAHs contained within fine particulates are etiologic (ATSDR, 1995; Choi, 2006).
IARC classifies naphthalene as a possible human carcinogen. NTP determined that naphthalene is reasonably anticipated to be a human carcinogen. Many other PAHs are considered to be probable or possible human carcinogens. IARC and NTP have classified specific PAH-containing chemical mixtures (e.g., soot, coke oven emissions, coal tars and coal tar pitches) as human carcinogens. OSHA has developed criteria on the allowable levels of these chemicals in the workplace.
Information about external exposure (i.e., environmental levels) and health effects is available in reviews (Bosetti et al., 2007; Bostrom et al., 2002; Brandt and Watson 2003) and from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.
| PAH Metabolites in the National Biomonitoring Program | |||
|---|---|---|---|
| Polycyclic Aromatic Hydrocarbon (CAS number) | Urinary hydroxylated metabolite (CAS number) | ||
| Fluorene (86-73-7) |
2-Hydroxyfluorene (2443-58-5) 3-Hydroxyfluorene (6344-67-8) 9-Hydroxyfluorene (484-17-3) |
||
| Naphthalene (91-20-3) |
1-Hydroxynapthalene (90-15-3) 2-Hydroxynapthalene (135-19-3) |
||
| Phenanthrene (85-01-8) |
1-Hydroxyphenanthrene (2433-56-9) 2-Hydroxyphenanthrene 3-Hydroxyphenanthrene (605-87-8) 4-Hydroxyphenanthrene (7651-86-7) |
||
| Pyrene (129-00-0) | 1-Hydroxypyrene (5315-79-7) | ||
Biomonitoring Information
Measurement of urinary metabolites reflects recent exposure to PAHs. Some of the parent PAHs can produce more than one measurable urinary metabolite, as shown in the Table. The hydroxylated metabolites of PAHs are excreted in human urine both as free hydroxylated metabolites and as hydroxylated metabolites conjugated to glucuronic acid and sulfate. Urine metabolite profiles can vary depending on the PAH source(s), but also have been found to vary between individuals experiencing similar exposures within the same workplace (Grimmer et al., 1997; Jacob and Seidel 2002).
Finding a measurable amount of one or more metabolites in the urine does not imply that the levels of the PAH metabolites or the parent PAH cause an adverse health effect. Biomonitoring studies of urinary PAHs provide physicians and public health officials with reference values so that they can determine whether or not people have been exposed to higher levels of PAHs than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
Naphthalene
CAS No. 91-20-3
General Information
Naphthalene is produced commercially from coal tar and petroleum. It is used in producing an assortment of chemicals: phthalate plasticizers, naphthalene sulfonates and dyes, the insecticide carbaryl, and synthetic leather tanning chemicals. Naphthalene is an intermediate in manufacturing several pharmaceuticals. Crystalline naphthalene has been used as a moth repellent. Naphthalene is the most abundant PAH in cigarette smoke (Ding et al., 2005), and it is present in fossil fuel smoke and exhaust fumes, especially from diesel and jet fuels. Non-occupational exposure typically occurs through inhaling ambient and indoor air, and cigarette smoke. Naphthalene can be absorbed through the skin as a result of handling moth repellent or wearing clothes stored with moth repellent. Workers may be exposed via inhalation or dermal absorption in settings such as naphthalene production, coal coking operations, and wood treatment with creosote.
In the body, naphthalene metabolism is complex, leading to biologically reactive metabolites and other metabolites that are excreted in the urine. In studies of workers, naphthalene air concentrations were correlated with 1- and 2-hydroxynaphthalene urine concentrations (Bieniek 1994; 1997). Both naphthalene and the insecticide carbaryl are metabolized to 1-hydroxynaphthalene, making it difficult to distinguish between these exposures in the general population (Meeker et al., 2007). In contrast, only naphthalene metabolism results in 2-hydroxynaphthalene in urine.
Humans can develop hemolytic anemia and jaundice after high dose naphthalene exposure by either inhalation or ingestion, or from skin exposure to clothing and bedding treated with naphthalene moth repellents (ATSDR, 2005). Exposure to naphthalene vapor can irritate the eyes and respiratory tract. High dose and chronic exposure in occupational settings can result in cataracts or lens opacities (ATSDR, 2005). OSHA has established a workplace standard. IARC considers naphthalene to be a possible human carcinogen, and NTP considers that it is reasonably anticipated to be a human carcinogen.
Biomonitoring Information
Urinary levels of 1-hydroxynaphthalene and 2-hydroxynaphthalene (1-naphthol and 2-naphthol, respectively) reflect recent exposure. Levels similar to those reported in NHANES 2001–2002 and 2003–2004 subsamples have been found in small studies of pre-school children, adolescents and non-occupationally exposed adults (Kang et al., 2002; Kim et al., 2003; Kuusimaki et al., 2004; Wilson et al., 2003). Smokers typically have urinary 1- and 2-hydroxynaphthalene levels that are about 2 to 3 times higher than nonsmokers in both occupationally exposed and general populations (Campo et al., 2006; Nan et al., 2001; Serdar et al., 2003a, 2003b). Depending on the intensity of exposure, workers exposed to naphthalene have been found to have geometric mean urinary 1- and 2-hydroxynaphthalene levels that range from around 2 to 100 times higher than the levels in the Fourth Report (Bieniek 1997; Elovaara et al., 2006; Nan et al., 2001; Serdar et al., 2003a).
Finding a measurable amount of 1- or 2-hydroxynaphthalene in the urine does not imply that the level causes an adverse health effect. Biomonitoring studies on levels of 1- and 2-naphthalene provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of naphthalene than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
References
Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological profile for naphthalene, 1-methylnaphthalene, and 2-methylnaphthalene. August 2005 (update) [online] Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp67.html. 5/26/09
Bieniek G. The presence of 1-naphthol in the urine of industrial workers exposed to naphthalene. Occup Environ Med 1994;51(5):357-359.
Bieniek G. Urinary napthols as an indicator of exposure to naphthalene. Scand J Work Environ Health 1997;23:414-420.
Campo L, Buratti M, Fustinoni S, Cirla PE, Martinotti I, Longhi O, et al. Evaluation of exposure to PAHs in asphalt workers by environmental and biological monitoring. Ann NY Acad Sci 2006;1076:405-420.
Ding YS, Trommel JS, Yan Xj, Ashley D, Watson CH. Determination of 14 polycyclic aromatic hydrocarbons in mainstream smoke from domestic cigarettes. Environ Sci Technol 2005;39:471-478.
Elovaara E, Mikkola J, Makela M, Paldanius B, Priha E. Assessment of soil remediation workers' exposure to polycyclic aromatic hydrocarbons (PAH): Biomonitoring of naphthols, phenanthrols, and 1-hydroxypyrene in urine. Toxicol Lett 2006;162:158-163.
Kang JW, Cho SH, Kim H, Lee CH. Correlation of urinary 1-hydroxypyrene and 2-naphthol with total suspended particulates in ambient air in municipal middle-school students in Korea. Arch Environ Health 2002;57(4):377-382.
Kim YD, Lee CH, Nan HM, Kang JW, Kim H. Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations. J Occup Health 2003;45(3):160-167.
Kuusimaki L, Peltonen Y, Mutanen P, Peltonen K, Savela K. Urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene as markers of exposure to diesel exhaust. Int Arch Occup Environ Health 2004;77(1):23-30.
Meeker JD, Barr DB, Serbar B, Rappaport SM, Hauser R. Utility of urinary 1-naphthol and 2-naphthol levels to assess environmental carbaryl and naphthalene exposure in an epidemiology study. J Expo Sci Eviron Epidemiol 2007;17(4):314-20.
Nan HM, Kim H, Lim HS, Choi JK, Kawamoto T, Kang JW, et al. Effects of occupation, lifestyle and genetic polymorphisms of CYP1A1, CYP2E1, GSTM1 and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentrations. Carcinogenesis 2001;22(5):787-793.
Serdar B, Egeghy PP, Waidyanatha S, Gibson R, Rappaport SM. Urinary biomarkers of exposure to jet fuel (JP-8). Environ Health Perspect 2003a;111(14):1760-1764.
Serdar B, Waidyanatha S, Zheng Y, Rappaport SM. Simultaneous determination of urinary 1- and 2-naphthols, 3- and 9-phenanthrols, and 1-pyrenol in coke oven workers. Biomarkers 2003b;8(2):93-109.
