Toluene

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non guideline, non-GLP studies contributing to a weight of evidence

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Differences following skin or inhalation exposure in the absorption and excretion kinetics of trichloroethylene and toluene

Author:

Sato A, Nakajima T

Year:

1978

Bibliographic source:

Br. J. Ind. Med. 35, 43-49.

Reference 2

Reference Type:

publication

Title:

Exposure of animals and man to toluene.

Author:

Carlsson A, Lindqvist T

Year:

1977

Bibliographic source:

Scand. J. Work. Environ. Health 3, 135- 143.

Reference 3

Reference Type:

publication

Title:

Experimental exposure to toluene: further consideration of cresol formation in man

Author:

Woiwode W, Drysch K.

Year:

1981

Bibliographic source:

Br. J. Ind. Med. 38, 194-197

Reference 4

Reference Type:

publication

Title:

Toluene toxicological profile

Author:

ASTDR

Year:

2000

Bibliographic source:

US Dept Health and Human Services

Reference 5

Reference Type:

publication

Title:

Toluene risk assessment report

Author:

EU RAR

Year:

2003

Bibliographic source:

European Union Risk Assessment Report, Volume 30

Materials and methods

Endpoint addressed:

basic toxicokinetics

Principles of method if other than guideline:

The data for toxicokinetics, metabolism and distribution of toluene conform with the requirements of Annex VIIA of Directive 67/548/EEC

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Toluene

EC Number:

203-625-9

EC Name:

Toluene

Cas Number:

108-88-3

Molecular formula:

C7H8

IUPAC Name:

toluene

Results and discussion

Results:

Toluene is absorbed rapidly from the lung (approximately 50% absorbed), but uptake from skin exposure is limited. Toluene is almost completely absorbed from the gastrointestinal tract. Toluene is readily metabolised, mainly to benzoic acid. A proportion of around 20% of absorbed toluene is eliminated in expired air and the remaining 80% is metabolised and excreted in the urine.

Any other information on results incl. tables

The major uptake of toluene vapour is through the respiratory system. Studies in humans (e.g. Carlsson and Lindqvist, 1977) have shown that at rest a three-hour exposure to toluene vapour will result in an uptake amounting to approximately 50% of the inhaled toluene. Data from experimental exposure of volunteers show that physical work results in increased toluene uptake (Carlsson, 1982). Using a 50 W workload, exposure to 300 mg/m3 (80 ppm) toluene for 2 h toluene uptake was 2.4 times higher than the uptake at rest.  Liquid toluene can be absorbed through the skin. In five volunteers exposed to toluene by immersing a hand up to the wrist in liquid toluene for 30 minutes, maximum concentrations of toluene in blood (0.17 mg/L) were found 30 minutes after start of the exposure. The maximum blood toluene concentration was maintained for 10-15 minutes after exposure had ended and was a quarter of that achieved in a 2 h inhalation exposure to 100 ppm (377 mg/m3) toluene vapour (Sato and Nakajima, 1978). Dermal absorption from toluene vapours is not likely to be an important route of exposure. Biotransformation of toluene occurs mainly by oxidation. The endoplasmic reticulum of liver parenchymal cells is the principal site of oxidation which involves the P450 system. Analysis of blood and urine samples from workers and volunteers exposed to toluene via inhalation in concentrations ranging from 100 to 600 ppm (377-2,261 mg/m3) indicate that of the biotransformed toluene, ~ 99% is oxidised via benzyl alcohol and benzaldehyde to benzoic acid. The remaining 1% is oxidised in the aromatic ring, forming ortho-, meta- and para-cresol (Woiwode and Drysch, 1981).

Applicant's summary and conclusion

Conclusions:

Toluene is absorbed rapidly from the lung (approximately 50% absorbed), but uptake from skin exposure is limited. Toluene is readily metabolised, mainly to benzoic acid. A proportion of around 20% of absorbed toluene is eliminated in expired air and the remaining 80% is metabolised and excreted in the urine.

Executive summary:

Toluene is absorbed rapidly via inhalation and the amount absorbed (approximately 50%) depends on pulmonary ventilation. Toluene is almost completely absorbed from the gastrointestinal tract. Dermal absorption of toluene vapours is not likely to be an important route of exposure. Toluene is distributed to various tissues, the amount depending on the tissue/blood partition coefficient, the duration and level of exposure, and the rate of elimination. The half-life in human tissue may be up to three days, whereas blood toluene rapidly declines after cessation of exposure. A proportion (around 20%) of the absorbed toluene is eliminated in the expired air. The remaining 80% of the absorbed toluene is metabolised in the liver by the P450 system, mainly via benzyl alcohol and benzaldehyde to benzoic acid. Benzoic acid is conjugated with glycine and excreted in the urine as hippuric acid. There are no indications of particular species differences in the toxicokinetics, metabolism or distribution of toluene.