Biomonitoring Summary

Toluene

CAS No. 108-88-3

General Information

Toluene (methylbenzene) is a flammable, liquid, aromatic hydrocarbon. It is a high production chemical isolated from crude oil. Toluene is used widely as a solvent and to synthesize chemicals such as benzene, trinitrotoluene, and toluene diisocyanate. As with other aromatic solvents, it is a minor component of gasoline, and additives containing toluene are used as octane boosters. Toluene is detected frequently in urban air, especially in high motor traffic areas and near industrial areas or hazardous waste sites (ATSDR, 2000; Mukund et al., 1996). Indoor air levels of toluene can exceed outdoor levels, largely due to consumer products (e.g., nail polish solvent, adhesive glues, paints, and paint thinner) and cigarette smoke (ATSDR, 2000; Gordon et al., 1999). Toluene does not persist in soil due to its volatility and is not detected commonly in U.S. groundwater and drinking water supplies (USGS, 2006).

The general population is exposed to toluene mainly by breathing contaminated air. Workplace exposure to toluene may occur during the production and use of petrochemicals and solvents. Toluene is well absorbed by inhalation, dermal, and oral exposure routes. After absorption, toluene is metabolized rapidly by hepatic microsomal enzymes, and the major urinary excretion product is hippuric acid. Other urinary metabolites include ortho- and para-cresol, S-benzylmercapturic acid, and S-para-toluylmercapturic acid.

Human health effects from toluene at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Humans exposed to high levels of toluene in air for a short time can show central nervous system depression (lassitude, stupor, and coma). Persons with short term exposures to toluene at levels higher than workplace air standards have shown poor performance on cognitive tests, neurobehavioral impairment, and eye and upper respiratory tract irritation (ATSDR, 2000). Its distinctive aromatic smell is detectable well below workplace air standards. Chronic solvent inhalant abuse, usually involving toluene and other volatile hydrocarbons, has resulted in permanent brain damage with dementia (Filley et al., 2004). Chronic occupational exposures at levels exceeding workplace standards have damaged hearing and possibly color vision (Lomax et al., 2004). In animal studies, prenatal toluene exposure impaired fetal growth and skeletal development, and altered behavioral development in the offspring (ADSDR, 2000; Jones and Balster, 1997). Evidence for human reproductive effects is inconclusive, and reports of developmental effects have been reported mainly in children exposed in utero by maternal solvent abuse (Bukowski, 2001). Epidemiologic studies of workers exposed to toluene (or toluene together with other solvents) have not demonstrated increased risks for cancer, and animal studies have not demonstrated an increased incidence of tumors (IARC, 1999). IARC determined that toluene was not classifiable with regard to human carcinogenicity. The U.S. EPA has established a drinking water and other environmental standards for toluene. The FDA has established a bottle water standard and level for toluene as an indirect food additive. OSHA and ACGIH established workplace standards and guidelines, respectively, for toluene. Information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Levels of blood toluene reflect recent exposure. A nonrepresentative sample of adults in NHANES III (1988-1994) had geometric mean and median blood toluene levels, respectively, of 0.52 and 0.28 µg/L (Ashley et al., 1994; Churchill et al., 2001), generally higher than comparable levels in NHANES 2001-2002, 2003-2004, and 2005-2006. Similar median blood toluene levels have been reported in U.S. children (Sexton et al., 2005, 2006) and in studies of adults without occupational exposure (Backer et al., 1997; Bonanno et al., 2001; Buckley et al., 1997). Population studies in Italy and Mexico have reported median blood toluene levels that were about twice as high as those in the U.S. (Brugnone et al., 1994; Carrer et al., 2000; Lemire et al., 2004; Perbellini et al., 2002). Geometric mean blood toluene levels were 0.191 and 0.669 ng/mL in non-smoking and smoking adults, respectively, from a subsample of NHANES 1999-2000 participants (Lin et al., 2008). Other studies have reported blood toluene levels that were approximately four times higher in smokers than non-smokers (Ashley et al., 1995; Bonanno et al., 2001; Brugnone et al., 1994; Perbellini et al., 2002), but environmental tobacco smoke exposure has not been associated with elevated blood toluene levels (Carrer et al., 2000; Sexton et al., 2005). Exposure to gasoline fumes can increase blood toluene levels during self-service refueling (Backer et al., 1997). Vehicle exhaust and gasoline fumes in such occupational settings as gas stations, automobile repair shops, and street vending can result in blood toluene levels that are two to three times higher than background levels (Mannino et al., 1995; Romieu et al., 1999).

Finding a measureable amount of toluene in blood does not imply that the level of toluene causes an adverse health effect. Biomonitoring studies of blood toluene 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 toluene 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 toluene update. September 2000 [online]. Available at URL: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=161&tid;=29. 8/3/12

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, 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.

Bukowski JA. Review of the epidemiological evicdence relating toluene to reproductive outcomes. Regul Toxicol Pharmacol 2001;33(2):147-156.

Carrer P, Marconi 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.

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.

Filley CM, Halliday W, Kleinschmidt-DeMasters BK. The effects of toluene on the central nervous system. J Neuropathol Exp Neurol 2004;63(1):1-12.

Gordon SM, Callahan PJ, Nishioka MG, Brinkman MC, O'Rourke MK, Lebowitz MD, et al. Residential environmental measurements in the National Human Exposure Assessment Survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs. J Exp Anal Environ Epidemiol 1999;9:456-470.

International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 71. Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide Summary of Data Reported and Evaluation 1999 [online]. Available at URL: http://monographs.iarc.fr/ENG/Monographs/vol71/volume71.pdf. 8/3/12

Jones HE, Balster RL. Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene. Neurotoxicol Teratol 1997;19(4):305-313.

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, Meneses-Gonzalez F, et al. Environmental exposure of commuters in Mexico City to volatile organic compounds as assessed by blood concentrations, 1998. Salud Publica Mex 2004;46:32-38.

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):421-429.

Lomax FB, Ridgway P, Meldrum M. Does occupational exposure to organic solvents affect colour discrimination? Toxicol Rev 2004;23(2):91-121.

Mannino DM, Schreiber J, Aldous K, Ashley D, Moolenaar R, Almaguer D. Human exposure to volatile organic compounds: a comparison of organic vapor monitoring badge levels with blood levels. Int Arch Occup Environ Health 1995;67:59-64.

Mukund R, Kelly TJ, Spicer CW. Source attribution of ambient air toxic and other VOCs in Columbus, Ohio. Atmospheric Environment 1996;30(20):3457-3470.

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.

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.

United States Geological Survey (USGS). Volatile organic compounds in the nation's ground water and drinking-water supply wells. 2006 [online]. Available at URL: https://pubs.usgs.gov/circ/circ1292/. 8/3/12