Inhalation of toluene vapour can affect the central nervous system (CNS). 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, numbness, and mild nausea; and over 500 ppm has caused mental confusion and incoordination. Higher concentrations (estimated at higher than 10000 ppm) can result in unconsciousness and death. Most serious incidences of exposure have occurred when the vapour has accumulated in confined spaces.

In some studies, relatively high exposures (well above exposure limits) have affected performance on neurobehavioural tasks (for example, decreased performance on complex tasks and increased response time.

A review of studies on the effects of toluene exposure and colour vision concludes that short-term exposure to toluene does not have an effect on colour discrimination, even when exposures are relatively high.

In two cases of acute occupational exposure, there were no blood disorders, liver or kidney damage observed. Historical reports of blood effects caused by toluene are more than likely due to benzene contamination. Benzene is well known to be toxic to the blood. 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.

Toluene is a moderate skin irritant, based on animal information. Prolonged contact can cause dermatitis (dry, red skin). Absorption of toluene through the skin may contribute significantly to the overall exposure. Although no reports of harmful effects following skin absorption were located.

Toluene is a very mild eye irritant, based on animal evidence. In people, 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 or 150 ppm also caused slight irritation.

There are case reports of accidental ingestion of toluene causing severe central nervous system (CNS) depression and death. Toluene is readily absorbed following ingestion producing symptoms similar to those described for inhalation above. Toluene may be aspirated, which is the inhalation of a chemical 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) because of its defatting action.

NERVOUS SYSTEM: Numerous studies of rotogravure printers, painters and rubberized-matting workers with long-term exposure to toluene are inconclusive about the potential of toluene to cause central nervous system (CNS) damage. Most studies do not have good exposure data, several indicate alcohol consumption as a confounder and few have used the neurobehavioural tests recommended by the World Health Organization. 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 results actually indicate CNS damage is not clear. Other studies have shown no change in neurobehavioural measurements for workers with long-term exposure to toluene.

EYES/VISION: A review of several studies on toluene and its effects on colour vision concluded that the evidence is inconclusive as to whether long-term exposure to toluene results in a persistent impairment of colour vision

HEARING: Firm conclusions cannot be drawn based on the limited information available. Hearing loss has been observed in workers in some studies following long-term exposure to toluene and noise and in animals exposed to very high concentrations of toluene.

KIDNEY EFFECTS: Kidney effects are not expected to occur unless exposures are very high. In population studies of workers exposed long-term to levels up to 200 ppm, there was no clear evidence of kidney damage. There are reports of kidney damage in people exposed long-term to high concentrations of toluene as a result of solvent abuse (glue-sniffing). These extreme exposures are not relevant to occupational situations.

BLOOD SYSTEM: Recent studies do not show consistent effects on the blood from long-term toluene exposure. Effects noted in workers before the 1950s are attributed to exposure to benzene, a contaminant of toluene at that time.

LIVER EFFECTS: Liver effects are not expected to occur unless exposures are very high. There is little evidence of liver damage in workers exposed to up to 500 ppm toluene or in people with long-term solvent abuse (glue-sniffing). Some studies indicate that long-term exposure to 30-350 ppm may result in increased levels of liver enzymes, an early indicator of liver injury. Liver effects have only been seen in animal studies involving long-term inhalation and ingestion exposure to relatively high concentrations.

Toluene is not considered carcinogenic.

There have been several human population studies that have examined the possible relationship between toluene exposure and cancer. Most types of cancer were not significantly associated with toluene exposure in any study. Stomach cancer mortality, lung cancer rates and colorectal cancers were elevated in some studies, but not others. Because most of the studies involved multiple exposures and there are inconsistencies in the findings, it is not possible to conclude that toluene exposure is associated with cancer in humans. The International Agency for Research on Cancer (IARC) has concluded there is inadequate evidence for the carcinogenicity of toluene in humans. Toluene did not cause tumours in rats and mice exposed by inhalation in a well-conducted study.

The International Agency for Research on Cancer (IARC) has concluded that this chemical is not classifiable as to its carcinogenicity to humans (Group 3).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as not classifiable as a human carcinogen (A4).

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Toluene is not considered a reproductive hazard. No conclusions can be drawn based on the available human information. Reproductive effects have not been observed in animal studies.

A review of toluene and its potential to cause reproductive toxicity in workers has been published. Three cross-sectional studies evaluated fertility in women exposed to toluene or in the wives of exposed men. No conclusions can be drawn based on these studies due to limitations such as selection bias, recall bias, and the fact that the workers were exposed to other potentially harmful chemicals. Another study suggests that menstrual function is not affected by exposure to toluene.

Toluene is a developmental toxicity hazard, based on information obtained from animal studies. Fetotoxicity (reduced fetal weight), behavioural effects (effects on learning and memory) and hearing loss (in males) have been observed in the offspring of rats exposed by inhalation to 1200 or 1800 ppm toluene. These effects were observed in the absence of maternal toxicity.

A detailed review of toluene and its potential to cause teratogenicity/embryotoxicity in occupational situations has been published. This review concludes that although many occupational studies have evaluated general solvent exposure and pregnancy outcomes, few studies have specifically investigated toluene exposure. Most of these studies have involved exposure to solvents in general or to certain solvent classes, with toluene exposure addressed as a co-exposure or identified as a common exposure in a sub-group. Outcomes of concern included miscarriages and teratogenicity (congenital malformations).

Concerns about the potential teratogenicity of toluene in humans have also arisen due to effects (facial aberrations, reduced growth, neurobehavioural delay, renal/urinary problems) 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.

Combined exposure to toluene and noise, toluene and n-hexane, toluene and aspirin or toluene, ethylbenzene and noise has caused a synergistic loss of hearing in animal studies. Increased hearing loss has also been observed in workers in some studies following long-term exposure to toluene and noise.

Toluene is readily absorbed by inhalation, ingestion and through the skin.

Inhaled toluene appears quickly in the brain fat (lipid) where it is rapidly eliminated. The half-life in human adipose tissue is 0.5-2.7 days. Toluene is removed rapidly from the blood. It is metabolized in the liver where it is converted via several steps primarily to hippuric acid, which is excreted in the urine. A small amount of toluene is also exhaled unchanged. Toluene has been identified in human milk.