Hydrocarbons, C5-C7, n-alkanes, isoalkanes, n-hexane rich

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline available

GLP compliance:

not specified

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:

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.

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).

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C5-C7, n-alkanes, isoalkanes, n-hexane rich

EC Number:

930-397-4

Cas Number:

1174918-63-8

Molecular formula:

Combination of CnH2n+2 structures and comprised mainly within a carbon number range from C5 to C7.

IUPAC Name:

Hydrocarbons, C5-C7, n-alkanes, isoalkanes, n-hexane rich

Test material form:

liquid

Details on test material:

Name of substance - Hydrocarbons, C5-C7 n-alkanes, isoalkanes, n-hexane rich
EC number - 930-397-4

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:

This data is being read across from the source study that tested n-hexane based on analogue read across.

 

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).