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Biomonitoring Summary

Xylenes

CAS No. 1330-20-7

o-xylene CAS No. 95-47-6
m-xylene CAS No. 108-38-3
p-xylene CAS No. 106-42-3

General Information

Xylenes are aromatic chemicals that exist in three isomeric forms: o-, m-, and p-xylene. Commercial production results in mixed xylenes, which contain these three isomers, in addition to ethylbenzene and trace amounts of several non-xylene hydrocarbons. Specific xylene isomers are produced from mixed xylene and are used to synthesize other chemicals. Mixed xylenes are used widely as gasoline additives; as solvents in manufacturing and laboratory processes; in glues, adhesives, printing inks, paint thinners, and sealants; and as carrier solvents for delivery of some pesticides. Indoor air sources of xylene include building and consumer products, such as adhesives and paints, and also tobacco smoke (ATSDR, 2007). The most important route of exposure for the general population is inhaling volatized xylenes, although dermal contact with liquids containing xylene may also contribute. Workplace exposure to xylenes may occur when producing, transporting, and using petrochemicals and industrial solvents.

Following inhalational, dermal, or oral exposure, xylenes are well absorbed and then rapidly and widely distributed throughout the body tissues, especially adipose tissue. A fraction of an absorbed xylene dose is excreted unchanged in exhaled air, and about 90% of a dose is metabolized by the liver and then eliminated in urine over several days. Methylhippuric acids are the predominant urinary metabolites and have been used to monitor workplace exposures.

Human health effects from xylenes at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Among humans, accidental exposure to high levels of xylene in air can cause eye and mucous membrane irritation, dyspnea, and central nervous system effects, such as headaches, dizziness, forgetfulness, delayed reaction times, and poor coordination (ATSDR, 2007). Epidemiologic studies of cancer and xylene exposure have been inconclusive and are limited by small numbers, lack of exposure measurements, and the concomitant exposure to other solvents (IARC, 1999). Animal studies involving high doses showed hepatic enzyme induction, liver enlargement, increased kidney weight and renal cytochrome P450 content, as well as neurobehavioral effects and altered catecholamine levels in the brain (ATSDR 2007). Pregnant animals that inhaled high doses had increased fetal resorption and offspring with skeletal abnormalities and decreased body weight (ATSDR 2007). Neurobehavioral effects resulted in laboratory animals exposed during gestation to xylene concentrations in the air that were about five times higher than U.S. occupational standards (Hass et al., 1997,1995). Animals exposed to high doses of technical grade xylene by gavage did not demonstrate an increase in the incidence of tumors (NTP, 1986).

Workplace standards for xylene levels in air have been established by OSHA, and ACGIH recommends a biological exposure index to monitor workplace exposure. The U.S. EPA has established a drinking water standard and other environmental standards for xylene. FDA has established a bottled drinking water standard. IARC has determined that xylene is not classifiable with regard to its human carcinogenicity. Information about external exposure (i.e., environmental levels) and health effects is available from ATSDR at: http://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Levels of blood xylenes reflect recent exposure. The m- and p- xylene isomers usually are measured together and reported as m/p-xylene; the o-xylene isomer is measured and reported separately. In the NHANES 2001-2002 and 2003-2004 subsamples, blood o-xylene was nondetectable in a majority of the participants, and in NHANES 2005-2006, the lower detection limits resulted in a higher percentage of participants with detectable results. The median blood m/p-xylene levels were similar to the earlier NHANES III results. In a nonrepresentative subsample of adults in NHANES III (1988-1994), the median blood levels of o-xylene and m/p-xylene were 0.11 µg/L and 0.19 µg/L, respectively (Ashley et al., 1994). These results were roughly similar to geometric mean levels of nonsmokers reported in a subsample of NHANES 1999-2000 (Lin et al., 2008) and in other studies of the U.S. general population (Bonanno et al., 2001; Buckley et al., 1997; Hamar et al., 1996), and to levels in adults in other countries (Lemire et al., 2002). Blood o-xylene levels in U.S. children were two to three times lower than adult levels (Sexton et al., 2005, 2006). Smokers can have blood o- and m/p-xylene levels that are each about twice as high as those for nonsmokers (Ashley et al., 1995; Bonanno et al., 2001; Lin et al., 2008). Workers who are exposed to vehicle exhaust can have o- and m/p-xylene blood levels that are each about two to three times higher than levels in the general population (Backer et al., 1997; Mannino et al., 1995; Romieu et al., 1999).

Finding a measurable amount of any of the xylenes in blood does not imply that the level of xylene causes an adverse health effect. Biomonitoring studies of blood xylenes 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 xylenes 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 xylene. 2007 [online]. Available at URL: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=296&tid=53. 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.

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.

Hamar GB, McGeehin MA, Phifer BL, Ashley DL. Volatile organic compound testing of a population living near a hazardous waste site. J Exp Anal Environ Epidemiol 1996;6(2):247-255.

Hass U, Lund SP, Simonsen L. Long-lasting neurobehavioral effects of prenatal exposure to xylene in rats. Neurotoxicology 1997;18(2):547-551.

Hass U, Lund SP, Simonsen L, Fries AS. Effects of prenatal exposure to xylene on postnatal development and behavior in rats. Neurotoxicol Teratol 1995;17(3):341-349.

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

Lemire S, Ashley D, Olaya P, Romieu I, Welch S, Meneses-Gonzalez F, Hernandez-Avila M. Environmental exposure of commuters in Mexico City to volatile orgnic compounds as assessed by blood concentrations, 1998. Salud Publica Mex 004;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):421-9.

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 Occp Environ Health 1995;67:59-64.

National Toxicology Program (NTP). Toxicology and carcinogenesis studies of xylenes (mixed) (60% m-xylene, 14% p-xylene, 9% o-xylene, and 17% ethylbenzene) (CAS No. 1330-20-7) in F344/N rats and B6C3Fl mice (gavage studies). 1986 [online]. Available at URL: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr327.pdf. 8/3/12

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.


 
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