The main effect of inhaling toluene vapour is on the central nervous system (CNS). Symptoms are related to exposure concentration. At approximately 50 ppm, slight drowsiness and headache have been reported. Irritation of the nose, throat and respiratory tract has occurred between 50 and 100 ppm. Concentrations of about 100 ppm have caused fatigue and dizziness; over 200 ppm has caused symptoms similar to drunkenness (giddiness), numbness, and mild nausea; over 500 ppm has caused mental confusion and incoordination. At higher concentrations (estimated at 10,000 ppm) further depression of the central nervous system can result in unconsciousness and death. Most serious incidences of exposure have occurred when vapours have accumulated in confined spaces.

In two cases of acute occupational exposure, there were no blood disorders, liver or kidney damage. Historical reports of blood effects caused by toluene are more than likely due to benzene contamination. Liver and kidney effects, as well as heart disturbances, have been reported in cases of solvent abuse (glue-sniffing). Reversible kidney failure has resulted from a severe occupational exposure in a paint factory.

Skin contact may result in mild irritation initially. Prolonged contact is more irritating due to the defatting action of this solvent and dermatitis (dry, red skin) may result. Liquid toluene is absorbed through the skin slowly. Therefore, other toxic effects would not be expected by this route of exposure. Despite widespread use of toluene, there are no reports of skin sensitization.

Very short exposure (3 to 5 minutes) to the vapour has caused slight eye irritation at 300 ppm. Longer exposures (6 to 7 hours) to concentrations above 100 ppm have also caused slight irritation. Animal studies indicate that splashes of toluene in the eyes will be irritating but will not cause permanent injury.

Toluene is readily absorbed following ingestion producing CNS depression. Symptoms will be similar to those described for inhalation. Toluene may cause aspiration, which is the inhalation of a material into the lungs during ingestion or vomiting. Severe lung irritation, damage to the lung tissues and death may result. Ingestion of approximately 60 mL (2 oz) toluene was fatal to an adult within 30 minutes in one reported case. The authors state that the probable cause of death was depression of the central nervous system. However, it is possible that the toluene was aspirated and death was caused by aspiration.

SKIN: Repeated or prolonged contact may cause dermatitis (red, itchy, dry skin).

NERVOUS SYSTEM: Numerous studies of rotogravure printers, painters and rubberized-matting workers with chronic exposure to toluene are inconclusive about chronic CNS damage. Some studies report changes such as memory loss, sleep disturbances, loss of ability to concentrate, or incoordination, while others report no effects. Recent studies using sensitive neurobehavioural tests have shown altered scores for exposed workers but whether or not these indicate CNS damage is not clear.

VISION AND HEARING: Alterations in vision, for example, reduced acuity and suppressed colour vision, have been documented following exposure to mixed solvents. It is not possible to attribute these effects to toluene directly. There is some evidence to suggest that long-term exposure to toluene may affect hearing. However, the limited information available does not allow a conclusion to be drawn.

KIDNEY EFFECTS: Most studies reporting kidney damage in people result from solvent abuse (for example, glue-sniffing). These extreme exposures are not relevant to occupational situations. In epidemiological studies on workers exposed long-term to levels up to 200 ppm, there was no clear evidence of kidney damage.

BLOOD SYSTEM: Although minor changes in blood parameters have been observed, it is generally accepted that toluene does not cause significant blood disorders.

LIVER EFFECTS: Occupational exposure to up to 500 ppm toluene has not been associated with liver effects.

There have been a few epidemiological investigations as to the carcinogenicity of toluene. However, the studies have been limited by several factors including combined exposures, small study populations and lack of exposure data. Toluene was not found to be carcinogenic in animal studies.

The International Agency for Research on Cancer (IARC) has determined that there is inadequate evidence for the carcinogenicity of toluene in humans. OVERALL IARC EVALUATION: Toluene is not classifiable as to its carcinogenicity to humans.

One epidemiological study suggests that menstrual function is not affected by exposure to toluene. More research is required to confirm this finding.

There is one report of testicular atrophy and reduced spermatogenesis in one man who abused toluene for 10 years. This extreme situation is not relevant to occupational exposures.

Most concerns about teratogenicity have arisen about effects (usually renal/urinary) seen in solvent abuse cases (glue- sniffing). These extreme exposures to toluene, as well as other confounding factors such as tobacco and alcohol abuse, are not relevant to occupational situations.

In epidemiological studies of women who had children with birth defects or had increased spontaneous abortions, it was discovered that the women were exposed to organic solvents, including toluene, during their pregnancy. However, no conclusions can be drawn from these studies, largely because of the mixed exposures, the small number of cases studied and the appropriateness of the control group. Further research is required to clarify these findings.

Exposure to other solvents such as benzene, xylene and ethanol (alcohol) slows the rate of clearance of toluene from the body, thereby enhancing the toxicity of toluene.

Toluene is readily absorbed by inhalation or ingestion and tends to be deposited more in tissues that are fatty or have a rich blood supply (e.g. brain, liver, kidney, fat). There was no evidence of accumulation in rats with repeated inhalation exposure to 300 ppm. Toluene is metabolized in the liver and excreted by the kidneys in the urine. It can also be exhaled unchanged.