Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
other:
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Measured levels in air for n-hexane and metabolites in urine of exposed worker but no information provided regarding GLP or ethical approvals.

Data source

Reference
Reference Type:
publication
Title:
Urinary excretion of the metabolites of n-hexane and its isomers during occupational exposure
Author:
Perbellini, L, Brugnone, F, Faggionato, G.
Year:
1981
Bibliographic source:
Brit J Indust Med 38:20-26.

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Ethical approval:
not specified
Details on study design:
Solvent levels measured in several workplace locations in shoe factories. Urine was collected from workers at the end of afternoon shift. Metabolites of hexane were tested in the urine samples using acid extraction.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: Inhalation

TYPE OF EXPOSURE MEASUREMENT: Area air sampling and Biomonitoring (urine)

EXPOSURE LEVELS: 32–500 mg/m3 n-hexane; mean concentration was 183 mg/m3; median was 1600 mg/m3

EXPOSURE PERIOD: 1 day

Results and discussion

Results:
Metabolism of n-hexane in humans primarily forms 2,5-hexanedione according to this study, which identified this metabolite along with 2,5-dimethylfuran, (-valerolactone, and 2-hexanol in the urine of 41 shoe workers exposed to hexane solvents that contained n-hexane. The mean concentrations, determined following acid extraction of the urine, were 5.4 ± 4.9, 3.7 ± 4.1, 3.3 ± 2.7, and 0.19 ± 0.26 mg/L, respectively. n-Hexane exposure correlated well both with total metabolites (r = 0.7858) and with 2-hexanol (r = 0.6851) and 2,5-hexanedione (r = 0.6725) individually.

Applicant's summary and conclusion

Executive summary:

Perbellini et al. (1981) measured metabolites in shoe workers exposed to n-hexane. Mean concentrations of n-hexane metabolites in urine were: 2,5-hexanedione, 5.4 mg/L; 2,5-dimethylfuran, 3.7 mg/L; gamma-valerolactone, 3.3 mg/L; and 2-hexanol, 0.19 mg/L. (2,5-Dimethylfuran and gammavalerolactone were believed to be artifacts of sample preparation and analysis rather than true metabolites of nhexane) (ATSDR 1999). The first reaction that takes place is hydroxylation of n-hexane at the 2 position to form 2-hexanol. Further reactions result in 2,5-hexanedione, presumably through transient intermediates, including 2-hexanone, 2,5-hexanediol, and 5-hydroxy-2-hexanone. Correlations between concentrations of n-hexane in air and urinary metabolites were best for total n-hexane metabolites (r=0.7858), followed by 2 -hexanol (r=0.6851) and 2,5 -hexanedione (r=0.6725).