N-hexane

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Urinary excretion of 2,5-hexanedione and peripheral polyneuropathies in workers exposed to hexane.

Author:

Governa, M, Calisti, R, Coppa, G, Tagliavento, G, Colombi, A, Troni, W

Year:

1987

Bibliographic source:

J. Toxicol. Environ. Health 320:219-228

Materials and methods

Study type:

case control study (prospective)

Endpoint addressed:

neurotoxicity

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N-hexane

EC Number:

203-777-6

EC Name:

N-hexane

Cas Number:

110-54-3

Molecular formula:

C6H14

IUPAC Name:

hexane

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

Investigation of the correlation between electrographic changes indicative of polyneuropathy and urinary excretion of metabolites indicative of exposure to n-hexane. Forty workers were randomly chosen from four small shoe factories. All workers handled a type of glue or solvent that contained over 50% n-hexane without protective equipment for about 7 hours/day. All subjects exhibited no more than mild or nonspecific symptoms of polyneuropathy and were free of other known risk factors for nervous system impairment. A urine sample was collected at the end of a shift, and then a neurophysiological examination (MCV, SCV, and associated distal latencies [DL]) was carried out the following day. Reference values were obtained from 41 unexposed individuals.

Exposure assessment:

measured

Details on exposure:

Air concentrations were not measured. Urinary levels of metabolites were measured using acid extraction method described in Perbellini et al. (1981)

Statistical methods:

Urinary concentrations of the substances tested did not have a normal distribution. Therefore, correlations between urinary levels of metabolites of n-hexane and electrodiagnostic scores were tested by Kendall's t with blocking variable.

Results and discussion

Results:

EXPOSURE
- Number of measurements: 1 urine sample per study subject (40 subjects) at end of weekly shift
- Average concentrations: 6.80 mg/L 2,5-hexanedione in urine
- Median: 6.60 mg/L 2,5-hexanedione in urine
- Standard deviation: 4.62 mg/L 2,5-hexanedione in urine
- Extreme values: 0.50 to 19.00 mg/L 2,5-hexanedione in urine
- Date(s) of measurement(s): 2 or 4

FINDINGS: A statistically significant correlation of the electroneuromyographic scoring on the concentrations of measured metabolites in urine was observed only with 2,5-hexanedione and gamma-valerolactone, the latter of which is probably not a true metabolite of n-hexane. The results support the conclusion that polyneuropathies in shoemakers are due to 2,5-hexanedione.

Confounding factors:

Based on case histories, seven workers were excluded who had former or actual neurological diseases different from polyneuropathy, diabetes, alchol abuse, or potentially neurotoxic medication. In the 40 workers evaluated, none had evidence of previous occupational contact to any known neurotoxic industrial substance.

Applicant's summary and conclusion

Executive summary:

Governa et al. (1987) investigated the correlation between electrographic changes indicative of polyneuropathy and urinary excretion of metabolites indicative of exposure to n-hexane. Forty workers were randomly chosen from four small shoe factories. All workers handled a type of glue or solvent that contained over 50% n-hexane without protective equipment for about 7 hours/day. All subjects exhibited no more than mild or nonspecific symptoms of polyneuropathy and were free of other known risk factors for nervous system impairment. A urine sample was collected at the end of a shift, and then a neurophysiological examination (MCV, SCV, and associated distal latencies [DL]) was carried out the following day. Reference values were obtained from 41 unexposed individuals. The urinary concentrations n-hexane metabolites were measured in 40 workers, but only those for two of the five n-hexane metabolites were above minimum detection limits (MDLs): 2,5-hexanedione (mean, 6.80 mg/L) and (valerolactone (mean, 3.31 mg/L). A statistically significant dose-response relationship for the electroneuromyography (ENM) scores was found for 2,5 -hexanedione and valerolactone. A threshold value of 7.5 mg/L was closely related to the incidence of abnormalities. Some variation from the relationship was apparent because three workers with lower concentrations of 2.5 -hexanedione (3.0, 3.3, and 4.5 mg/L) displayed ENM changes.