Biomonitoring Summary

Benzene

CAS No. 71-43-2

General Information

Benzene is a volatile chemical that is produced commercially from coal and petroleum sources. It is among the most abundantly produced chemicals in the U.S. and is used extensively as an industrial solvent, in the synthesis of numerous chemicals, and as an additive in unleaded gasoline (ATSDR, 2007).

Human exposure occurs primarily by inhaling benzene in ambient air (Hattemer-Frey et al., 1990; Wallace, 1996). Sources of benzene in the air may result from either natural (e.g., forest fires) or industrial sources. Among industrial sources, automobile emissions and vapor around gasoline filling stations contribute to benzene in air (ATSDR, 2007). Tobacco smoke contributes to benzene in indoor air (Duarte-Davidson, et al., 2001), and tobacco smoke is estimated to account for about half of the total estimated exposure to benzene (ATSDR, 2007). Indoor sources for benzene, which include the offgassing of building materials, account for a significant portion of a non-smoker's benzene exposure (Wallace, 1996; Wallace et al., 1987). The consumption of food, drinking water, and beverages are considered negligible sources of exposure unless benzene contamination has occurred, such as from leaking underground fuel storage tanks (ATSDR, 2007; Wallace, 1996). In recent years, less than five percent of domestic wells used for drinking water in the U.S. have been found to contain detectable amounts of benzene (Rowe et al., 2007). Workplace exposure to benzene may result from production, use, or transportation of petroleum products.

Benzene is well absorbed after inhalational, oral, or dermal exposure. In the blood, benzene is distributed rapidly throughout the body, especially into the brain and fatty tissues, and can cross the placenta. Benzene is metabolized in the liver, and some metabolites may be distributed to the bone marrow, where additional metabolism may result in toxic effects on hematopoietic cells (ATSDR, 2007; Ross, 2000). The primary benzene metabolites are phenol, catechol, hydroquinone, 1,2,4-benzenetriol, and to a lesser extent, trans, trans-muconic acid, which are eliminated in urine as glucuronide and sulfate conjugates (Ross, 2000). Urinary S-phenylmercapturic and t,t- muconic acids are used for monitoring workplace exposure. A very small amount of unchanged benzene is eliminated in the breath.

Accidental and intentional exposures to high concentrations of benzene vapor can lead rapidly to euphoria, central nervous system depression, cardiac arrhythmias, followed by unconsciousness and death (ATSDR, 2007). Workers have developed skin irritation following repeated dermal exposure and mucous membrane irritation following repeated vapor inhalation (ATSDR, 2007). Epidemiologic studies of workers in industries involving benzene have found that benzene exposure can cause bone marrow suppression and increases the risk of various leukemias (Savitz and Andrews, 1997). Supportive evidence for benzene carcinogenicity comes from animal studies and from in vitro studies demonstrating the clastogenic properties of benzene on blood forming cells (NTP, 1986; Ross, 2000). The background exposure levels for the general population have been estimated to be much lower than the estimated lowest effect level for benzene at which leukemia risk is increased (Duarte-Davidson, et al., 2001).

Workplace standards and guidelines for benzene have been established by OSHA and ACGIH, respectively. The U.S. EPA has established environmental and drinking water standards for benzene, and the FDA has established a bottled water standard. Benzene is classified as a known human carcinogen by IARC and by NTP. Information about external exposure (ie., environmental levels) and health effects is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Levels of blood benzene reflect recent exposure. The median levels of blood benzene observed in the NHANES 2001-2006 subsamples appear slightly lower than the median level in a nonrepresentative subsample of adults in NHANES III (1988-1994) (Ashley et al., 1994; CDC, 2012), as well for other previous studies of the U.S. general population (Bonanno et al., 2001; Buckley et al., 1997; Sexton et al., 2005 and 2006; Lin et al., 2008), and studies from other countries (Brugnone et al., 1994; Navasumrit et al., 2005).

Smoking, residing, or working in urban areas and exposure to gasoline and petroleum products can result in blood benzene levels that are higher than those in the nonsmoking general population (Ashley et al., 1995; Carrer et al., 2000; Backer et al., 1997). The amount and duration of cigarette smoking increases the likelihood of higher blood benzene levels (Bonanno et al., 2001; Churchill et al., 2001; Lin et al., 2008). Workers exposed to gasoline fumes, such as garage mechanics, drivers, and street vendors, and workers exposed to solvent fumes have been found to have blood benzene levels as much as tenfold higher than levels in the general population (Brugnone, et al., 1994 and 1999; Moolenaar et al., 1997; Perbellini et al., 2002; Romieu et al., 1999).

Finding a measurable amount of benzene in blood does not imply that the level of benzene causes an adverse health effect. Biomonitoring studies of blood benzene can 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 benzene than levels 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 benzene update. 2007 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=40&tid;=14. 10/16/12

Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Wooten JV. Blood concentrations of volatile organic compounds in a nonoccupationally exposed US population and in groups with suspected exposure. Clin Chem 1994;40(7 Pt 2):1401-1404.

Ashley DL, Bonin MA, Hamar B, McGeehin MA. Removing the smoking confounder from blood volatile organic compounds measurements. Environ Res 1995;71:39-45.

Backer LC, Egeland GM, Ashley DL, Lawryk NJ, Weisel CP, White MC, et al. Exposure to regular gasoline and ethanol oxyfuel during refueling in Alaska. Environ Health Perspect 1997;105(8):850-855.

Bonanno LJ, Freeman NCG, Greenberg M, Lioy PJ. Multivariate analysis on levels of selected metals, particulate matter, VOC, and household characteristics and activities from the Midwestern states NHEXAS. Appl Occup Environ Hyg 2001;6(9):859-874.

Brugnone F. Benzene in blood as a biomarker of low level occupational exposure. Sci Tot Environ. 1999;235:247.

Brugnone F, Perbellini L, Giuliari C, Cerpelloni M, Soave M. Blood and urine concentrations of chemical pollutants in the general population. Med Lav 1994;85(5):370-389.

Buckley TJ, Liddle J, Ashley DL, Paschal DC, Burse VW, Needham LL. Environmental and biomarker measurements in nine homes in the lower Rio Grande Valley: multimedia results for pesticides, metals, PAHs and VOCs. Environ Int 1997;23(5):705-732.

Carrer P, Maroni M, Alcini D, Cavallo D, Fustinoni S, Lovato L, et al. Assessment through environmental and biological measurements of total daily exposure to volatile organic compounds of office workers in Milan, Italy. Indoor Air 2000;10:258-268.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, 2012. [online] Available at URL: https://www.cdc.gov/exposurereport/. 10/1612

Churchill JE, Ashley DL, Kaye WE. Recent chemical exposures and blood volatile organic compound levels in a large population-based sample. Arch Environ Health 2001;56(2):157-166.

Duarte-Davidson R, Courage C, Rushton L, Levy L. Benzene in the environment: an assessment of the potential risks to the health of the population. Occup Environ Med 2001;58(1):2-13.

Hattemer-Frey HA, Travis CC, Land ML. Benzene: Environmental partitioning and human exposure. Environ. Res 1990;53:221-232.

Lin YS, Egeghy PP, Rappaport SM. Relationships between levels of volatile organic compounds in air and blood from the general population. J Expo Sci Environ Epidemiol 2008;18(4):421-9.

Moolenaar RL, Brockton JH, Ashley DL, Middauth JP, Etzel RA. Blood benzene concentrations in workers exposed to oxygenated fuel in Fairbanks, Alaska. Int Arch Occup Environ Health 1997;69:139-143.

National Toxicology Program (NTP). Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2) in F344/N rats and B6C3F1 mice (gavage studies). National Toxicology Program Tech Rep Series No. 289. 1986 [online]. Available at URL: https://www.ncbi.nlm.nih.gov/pubmed/12748714. 10/16/12

Navasumrit P, Chanvaivit S, Intarasunanont P, Arayasiri M, Lauhareungpanya N, Parnlob V, et al. Environmental and occupational exposure to benzene in Thailand. Chem Biol Interact. 2005;153-154:75-83.

Perbellini L, Pasini F, Romani S, Princivalle A, Brugnone F. Analysis of benzene, toluene, ethylbenzene and m-xylene in biological samples from the general population. J Chromat B 2002;778:198-210.

Romieu I, Ramirez M, Meneses F, Ashley DL, Lemire S, Colome S, et al. Environmental exposure to volatile organic compounds among workers in Mexico City as assessed by personal monitors and blood concentrations. Environ Health Perspect 1999;107(7):511-515.

Ross D. The role of metabolism and specific metabolites in benzene-induced toxicity: evidence and issues. J Toxicol Environ Health A 2000;61(5-6):357-372.

Rowe BL, Toccalino PL, Moran MJ, Zogorski JS, Price CV. occurrence and potential human-health relevance of colatile organic compounds in drinking water from domestic wells in the United States. Environ Health Perspect 2007;115(11):1539-1546.

Savitz DA, Andrews KW. Review of epidemiologic evidence on benzene and lymphatic and hematopoietic cancers. Am J Ind Med 1997 Mar;31(3):287-95.

Sexton K, Adgate JL, Church TR, Ashley DL, Needham LL, Ramachandran G, et al. Children's exposure to volatile organic compounds as determined by longitudinal measurements in blood. Environ Health Perspect 2005;113(3):342-349.

Sexton K, Adgate JL, Fredrickson AL, Ryan AD, Needham LL, Ashley DL. Using biologic markers in blood to assess exposure to multiple environmental chemicals for inner-city children 3-6 years of age. Environ Health Perspect 2006;114(3):453-459.

Wallace L. Environmental exposure to benzene: an update. Environ Health Perspect 1996;104 Suppl 6:1129-1136.

Wallace L, Pellizzari E, Leaderer B, Zelon H, Sheldon L. Emissions of volatile organic compounds from building materials and consumer products. Atmos Environ 1987;21:385-393.