Human Toxic Chemical Exposure - Toluene

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Reference Summary

Toluene, also known as methylbenzene, is an aromatic hydrocarbon solvent. It is widely used in industry, often as a substitute for benzene. Because of its methyl side group, it is metabolized differently than benzene, and may not cause cancer as benzene does. Toluene has the following structure:



Toluene is used in glues and adhesives, and is often the compound responsible for the effect that "glue sniffers” experience. Toluene may be encountered in the manufacture of benzene and is used in the production of detergents, pharmaceuticals, dyes, paints, textiles, plastics and many other substances.

Toluene may have local as well as systemic harmful effects. It may cause irritation of the eyes, respiratory tract, and skin. Repeated or prolonged contact with the liquid may cause removal of natural lipids from the skin resulting in dry, fissured dermatitis. Low-level, chronic exposure as well as acute exposure to toluene may result in central nervous system depression and decreased memory (1). Symptoms include headache, dizziness, fatigue, muscular weakness, drowsiness, and incoordination with staggering gait, skin paresthesia, collapse, and coma (2).

The Threshold Limit Value (that level below which no adverse health effects are expected) for toluene exposure is 100 ppm (about 375 mg/cu m) in the air as an 8-hour time-weighted average (4). Exposure levels necessary to produce physiological or toxicological effects are anticipated primarily in occupational or solvent abuse situations. It should be noted that the TLV is based upon information derived from acute, high-level exposure incidents, not chronic, low- level exposures.

Uptake and Metabolism

Toluene is very well absorbed through the lung, with an aveolar retention of 40-80% of an inhaled dose. With alcohol use during the exposure, the aveolar retention drops about 10% (4-5). Absorption of toluene through the skin can be appreciable: toluene applied to the forearm gives a dose equivalent to breathing over 30 ppm of vapor in the air.

With exercise, the amount of toluene uptake through the lungs is greatly increased. Thus, the correlation between toluene levels in the blood and in the ambient air will vary depending upon the level of exertion of the worker as well as the skin exposure.

Of an absorbed dose of toluene, about 20% is excreted unchanged by the lungs; the rest is metabolized primarily to hippuric acid. A very small percentage of the toluene is metabolized to cresol. Thus, the presence of o-cresol in the urine, a constituent not normally found in the human urine, can be used as a confirmatory test for toluene exposure (6).

Some toluene is stored in the human body fat and is eliminated from the fat, with a half-life of 1-3 days after exposure has ceased (5). However, neither has the clinical significance of this fat storage been investigated, nor has the level which is present in the fat of workers who have been chronically exposed been determined.

Human Toxic Chemical Exposure
The Bulletin of Pacific Toxicology Laboratories


Reference Summary
Toluene, also known as methylbenzene, is an aromatic hydrocarbon solvent. It is widely used in industry, often as a substitute for benzene. Because of its methyl side group, it is metabolized differently than benzene, and may not cause cancer as benzene does. Toluene has the following structure:



Toluene is used in glues and adhesives, and is often the compound responsible for the effect that "glue sniffers” experience. Toluene may be encountered in the manufacture of benzene and is used in the production of detergents, pharmaceuticals, dyes, paints, textiles, plastics and many other substances.

Toluene may have local as well as systemic harmful effects. It may cause irritation of the eyes, respiratory tract, and skin. Repeated or prolonged contact with the liquid may cause removal of natural lipids from the skin resulting in dry, fissured dermatitis. Low-level, chronic exposure as well as acute exposure to toluene may result in central nervous system depression and decreased memory (1). Symptoms include headache, dizziness, fatigue, muscular weakness, drowsiness, and incoordination with staggering gait, skin paresthesia, collapse, and coma (2).

The Threshold Limit Value (that level below which no adverse health effects are expected) for toluene exposure is 100 ppm (about 375 mg/cu m) in the air as an 8-hour time-weighted average (4). Exposure levels necessary to produce physiological or toxicological effects are anticipated primarily in occupational or solvent abuse situations. It should be noted that the TLV is based upon information derived from acute, high-level exposure incidents, not chronic, low- level exposures.



Uptake and Metabolism
Toluene is very well absorbed through the lung, with an aveolar retention of 40-80% of an inhaled dose. With alcohol use during the exposure, the aveolar retention drops about 10% (4-5). Absorption of toluene through the skin can be appreciable: toluene applied to the forearm gives a dose equivalent to breathing over 30 ppm of vapor in the air.

With exercise, the amount of toluene uptake through the lungs is greatly increased. Thus, the correlation between toluene levels in the blood and in the ambient air will vary depending upon the level of exertion of the worker as well as the skin exposure.

Of an absorbed dose of toluene, about 20% is excreted unchanged by the lungs; the rest is metabolized primarily to hippuric acid. A very small percentage of the toluene is metabolized to cresol. Thus, the presence of o-cresol in the urine, a constituent not normally found in the human urine, can be used as a confirmatory test for toluene exposure (6).

Some toluene is stored in the human body fat and is eliminated from the fat, with a half-life of 1-3 days after exposure has ceased (5). However, neither has the clinical significance of this fat storage been investigated, nor has the level which is present in the fat of workers who have been chronically exposed been determined.

Biological Monitoring

Toluene can be measured in the blood, and the blood level used as an approximate gauge of the airborne concentration (5- 7). Blood is typically drawn at the end of a workshift. (See attached graph: "Toluene Levels in Blood During Exposure to Toluene Vapor.'') Blood levels decline very rapidly after exposure stops, with an initial half-life of 2-3 hours. A "Tentative Maximum Permissible Level" of toluene in venous blood has been proposed 1 ppm (8,9).

Hippuric acid is the major metabolite of toluene, and can be recovered in the urine. However, it is important to note that hippuric acid is a normal constituent of human urine; unexposed persons typically excrete about 1 gram of hippuric acid per gram of creatinine. During toluene exposure, the urinary hippuric acid concentration will increase, such that at the end of a workshift with a toluene level of 100 ppm, the urinary hippuric acid concentration will be about 2.0 to 2.5 grams per gram of creatinine.

Because there is considerable variation in this value, there is considerable overlap in the range of hippuric acid concentration between exposed workers and non-exposed workers. Therefore, urinary hippuric acid concentrations are helpful for monitoring groups of workers, but not individuals.

Both Lauwerys (8) and the ACGIH (9) have pro posed a maximum permissible level of 2.5 grams of hippuric acid per gram of creatinine in urine as a biological monitoring strategy for groups of workers. (See attached graph. ''Hippuric Acid Concentration in Urine.'')

References

1. Axelson, O., et. al., Current Aspects of Solvent Related Disorders. In Developments in Occupational Medicine (ed. Carl Zenz), Yearbook Medical Publishers Inc. , Chicago, Pp. 23759, 1977

2. U.S. Environmental Protection Agency, Toluene, Health and Environmental Effects Profile No. 160, Washington, D.C., Office of Solid Waste (April 30, 1980).

3. Natational Institute for Occupational Safety and Health, Criteria for a Recommended Standard: Occupational Exposure to Toluene, NIOSH Dec. No. 73 11023(1973).

4. Dossing, M. et. al., Effect of ethanol, cimetidine, and propanol on toluene metabolism in man, Int. Arch. Occup. Environ. Health 54: 309-31.5(1984).

5. Carlsson, A. and Ljungquist, E., Exposure to toluene: Concentration in subcutaneous adipose tissue, Scand. J. Work Erlviron. Health 8: 56-62(1982)

6. Angerer, J., Occupational chronic exposure to organic solvents: VII. Metabolism of toluene in man, Int. Arch. Occup. Environ. Health 43: 6367(1~79).

7. Wallen, M.: et. al., Coexposure to toluene and paraxylene-Uptake and elimination in man, Brit cT. Ind. Med., 42(2): 111-16(1985).

8. Lauwerys, R.R., Industrial Chemical Exposure: Guidelines for Biological Monitoring. Biomedical Publications, Davis, 1983.

9. American Conference of Governmental and Industrial Hygienists (ACGIH), Biological Exposure Indicies, Cincinnati, 1984. (BEI. pages 19-2l).

10. De Rosa, E. et. al., The validity of urinary metabolites as indicators of low exposure of toluene, Int. Arch. Occup. Environ. Health ·56: 13.5-145 1985).

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