Toluene, occupational exposure

Occupational and environmental exposure to chemicals can take place both indoors and outdoors. Occupational exposure is caused by the chemicals that are used and produced indoors in industrial plants, whereas nonoccupa-tional (and occupational nonindustrial) indoor exposure is mainly caused by products. Toluene in printing plants and styrene in the reinforced plastic industry are typical examples of the two types of industrial occupational exposures. Products containing styrene polymers may release the styrene monomer into indoor air in the nonindustrial environment for a long time. Formaldehyde is another typical indoor pollutant. The source of formaldehyde is the resins used in the production process. During accidents, occupational and environmental exposures may occur simultaneously. Years ago, dioxin was formed as a byproduct of production of phenoxy acid herbicides. An explosion in a factory in... 

Peripheral neuropathy has also occurred in humans as the result of solvent abuse of products containing -hexane (Altenkirch et al. 1977 Chang et al. 1998 Spencer et al. 1980). Clinical signs were very similar to those seen after occupational exposure however, signs of central nervous system toxicity may also be present due to other components in the inhaled mixtures, e.g., toluene (Spencer et al. 1980). 

The interaction of /2-hexane with toluene and trichloroethylene has also been examined in volunteers (Baelum et al. 1998). Exposure in these experiments was via a gastric feeding tube at controlled rates equivalent to what the authors stated would be delivered to the liver by inhalation exposure at Danish occupational exposure limits (50 ppm /7-hexane. 50 ppm toluene, and 30 ppm trichloroethylene). Coexposure to toluene and trichloroethylene slightly increased the area under the curve (AUC) representing concentration versus time for end exhaled /2-hexane air concentration, but urinary excretion of 2,5-hexanedione was unchanged. The only statistically significant interaction observed with /2-hexane was an 18% decrease in the urinary excretion of hippuric acid, a toluene metabolite. 

National Institute For Occupational Safety and Health Criteria for a Recommended Standard. . . Occupational Exposure to Toluene Diisocyanate. DHEW (NIOSH Pub No (HSM) 73-11022. Washington, DC, US Government Printing Office, 1973... 

Jimtrmen J et al Nervous system effects of long-term occupational exposure to toluene. Acta Neurol Scand 75 512-517, 1985... 

Maitre A, Berode M, Perdix A, et al Biological monitoring of occupational exposure to toluene diisocyanate. Int Arch Occup Environ Health 65 97-100, 1993... 

DeRosa E, Bartolucci GB, Sigon M, et al. 1987. Hippuric acid andortho- cresol as biological indicators of occupational exposure to toluene. Am J Ind Med 11 (5) 529-537. 

Measured airborne and blood concentrations of ethylbenzene in several occupational settings are presented in Tables 3 and 4, respectively. Most occupational exposures to ethylbenzene result from use of products containing technical grades of mixed xylenes. No ethylbenzene was found from off-gassing of cured paint in a hyperbaric pressure chamber under normal atmospheric pressure, but under higher pressures, levels of 0.4-4.5 ppm [1.7-19.5 mg/m ] were measured (Lillo et al., 1990). Silk screen operations were found to entail exposure levels of less than 4 mg/m (Verhoeff et al., 1988). Ethylbenzene may also be present in low-grade toluene preparations (Inoue et al, 1995). 

The NIOSH-recommended limit for occupational exposure is 0.035 milligrams per cubic meter (.035 mg/m ), which is the same as 5 parts per billion (ppb). There is no established OSHA permissible exposure limit (PEL) for HDI at this time however, a similar substance, toluene diisocyanate (TDI), has a PEL of 5 parts per billion (ppb). The American Conference of Governmental Industrial Hygienists (ACGDT) places the limit for HDI inhalation exposure at 5 ppb. 

Kazuyuki 0, Higashi T, Nakadate T, et al. 1992. Fom year follow-up of effects toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing worker. Int Arch Occup Environ Health 63 565-569. 

Persson P, Dalene M, Skarping G, et al. 1993. Biological monitoring of occupational exposure to toluene diisocyanate measmement of toluenediamine in hydrolysed urine and plasma by gas chromatography-mass spectrometry. Br J Ind Med 50(12) 1111-1118. 

The manufacture of butadiene-based polymers and butadiene derivatives implies potential occupational exposure to a number of other chemical agents, which vary according to product and process, including other monomers (styrene, acrylonitrile, chloroprene), solvents, additives (e.g., activators, antioxidants, modifiers), catalysts, mineral oils, carbon black, chlorine, inorganic acids and caustic solutions (Fajen, 1986a.b Roberts, 1986). Styrene, benzene and toluene were measured in various departments of... 

Small cohort studies of occupational exposures to a-chlorinated toluenes and benzoyl... 

According to the 1981-83 National Occupational Exposure Survey (NOES, 1997), as many as 2 million workers in the United States were potentially exposed to toluene (see General Remarks). Occupational exposures to toluene may occur in painting, varnishing, various cleaning operations, laboratories, car repair shops and many other workplaces where toluene is produced or used as solvent or intermediate to prepare other chemicals. Extensive occupational exposure data are presented in a previous monograph (lARC, 1989a). 

The American Conference of Governmental Industrial Hygienists (ACGIH) (1997) has recommended 188 mg/m as the 8-h time-weighted average threshold limit value, with a skin notation, for occupational exposures to toluene in workplace air. Values of 100— 380mg/m3 are used as standards or guidelines in other countries (International Labour Office, 1991). 

Bauchinger, M., Schmid, E., Dresp, J., Kolin-Gerresheim, J., Hauf, R. Suhr, E. (1982) Chromosome changes in lymphocytes after occupational exposure to toluene. Mutat. Res., 102, 439-445... 

Gerin, M., Siemiatycki, J., Desy, M. Krewski, D. (1998) Associations between several sites of cancer and occupational exposure to benzene, toluene, xylene and styrene results of a case-control study in Montreal. Am. J. ind. Med., 34. 144-156... 

Nise, G, Attewel, R., Skerfving, S. Orbsk, P. (1989) Elimination of toluene from venous blood and adipose tissue after occupational exposure. Br. J. ind. Med., 46, 407-411... 

Lind, P, Dalene, M., Sharping, G. Hagmar, L. (1996) Toxicokinetics of 2,4- and 2,6-toluene-diamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6-toluene diisocyanate. Occup. environ. Med., 53, 94-99... 

Omae, K., Nakadate, T., Higashi, T., Nakaza, M., Aizawa, Y. Sakurai, H. (1992a) Four-year follow-up of effects of toluene diisocyanate exposure on the respiratoiy system in polyurethane foam manufacturing workers I. Study design and results of the first cross-sectional observation. Int. Arch, occup. environ. Health, 63, 559-564... 

Occupational exposure to chemical substances almost invariably involves multiple chemicals. That situation may result in PK interactions, which may affect the relationship between the atmospheric concentration of the parent chemical and the associated biomarker concentration (Viau 2002). For example, such an interaction is known to occur between ethylbenzene and the xylene isomers (Jang et al. 2001). Commercial xylene contains about 20% ethylbenzene, which modifies the slope of the relationship between urinary methylhippuric acid (MHA) and airborne xylene concentrations. That kind of interaction is unlikely at the subparts-per-million exposure concentrations seen in the general population. But because the BEI for MHA was obtained from the relationship observed after exposure to commercial xylene, thereby taking the interaction into account, the slope of the relationship cannot be extrapolated to the subparts-per-million range. Similar PK interactions have been observed for other mixtures but only at concentrations nearing or exceeding the occupational exposure limits (Viau 2002), so it would be a priori reasonable to consider extrapolation of the relationship between biomarker concentrations and those of their parent chemicals. For example, Tardif et al. (1991) demonstrated that, provided inhalation exposure to a mixture of toluene and xylene was kept below their airborne occupational exposure limits, there were no PK interactions between the compounds that affected the linear relationship between airborne parent-chemical exposure and urinary-metabolite concentrations. However, such an interaction was apparent at higher concentrations. 

Organic solvents, which induce CYP2E1, are comprised of a few broad chemical classes, including hydrocarbons such as benzene and toluene, halogenated aliphatic compounds such as carbon tetrachloride and dichloroethane, aliphatic alcohols such as ethanol, and hydroxyethers such as 2-methoxyethanol. Industrial solvents are frequently mixtures of several compounds. The most frequent solvent-associated toxicity occurs from occupational exposure. A number of organic solvents have been examined for their effects on the immune system, and the requirement for their bioactivation to produce immunotoxicity has been well established. 

---