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Toxicological information

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

Referenceopen allclose all

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 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 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 Type:
publication
Title:
Toluene toxicological profile
Author:
ASTDR
Year:
2000
Bibliographic source:
US Dept Health and Human Services
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

Reference
Name:
Unnamed
Type:
Constituent

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.