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

Abstract

Forty shoe factory workers who were exposed to hexane were investigated to see if there was a correlation between electroneuromyographic changes indicative of neuropathy and urinary excretion of 2,5-hexanedione. Urinary samples were analyzed for the presence of the metabolic products of n-hexane and its isomers. Electrodiagnostic examination was carried out following the urinary sampling. A rating scale was used to obtain a cumulative numeric index of electrodiagnostic findings. 2,5-Hexanedione and gamma-valerolactone were discovered in all cases, while 2-hexanol was found in 11 cases. 2,5-Hexanedione was the main metabolite in most cases (39 of 40). Only in 1 case was a low level of 2-methyl-2-pentanol detected; 3-methyl-2-pentanol was never detected. Metabolic products of cyclohexane were present in about one-fifth of the cases, while trichloroethanol, a metabolic product of trichoroethylene, was nearly always present, all at very low concentrations. Electromyographic abnormalities significant for early detection of toxic polyneuropathy were found in 14 cases. A statistically significant correlation of the electroneuromyographic scoring on the urinary concentrations of measured metabolites was observed only with 2,5-hexanedione and gamma-valerolactone, both derived from n-hexane. Since gamma-valerolactone is probably not a true metabolite of n-hexane, our results support the hypothesis that polyneuropathies in shoemakers are due to 2,5-hexanedione. For practical purposes the urinary concentration of 2,5-hexanedione can serve as a predictive measurement for early detection of neurotoxic lesions at preclinical states.

Scientific Opinion on Flavouring Group Evaluation 9, Revision 3 (FGE.09Rev3): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivative from chemical group 25

“…Workers employed in a shoe factory were exposed to small amounts of cyclohexane in the air. Cyclohexanol and cyclohexanone were found in the urine of these workers, indicating that the same metabolic pathways are also found in humans (Governa et al, 1987). A recent study in humans shows that the main metabolite in urine after cyclohexanone or cyclohexanol exposure is not cyclohexanolglucuronide as in rabbit and rats, but 1,2-cyclohexanediol-glucuronide (Mráz et al, 1994;Mráz et al, 1998).…”

Peripheral neuropathy and visual evoked potential changes in workers exposed to n-hexane

“…8,9 In individuals exposed to n-hexane, the resultant damage to the peripheral nervous system has been blamed on this particularly dangerous neurotoxin. 10,11 The concentration of 2,5-hexanedione in urine has been used as a biological monitor for workers exposed to n-hexane. 12 In our study, the urinary 2,5-hexanedione concentration was 0.46 mg/L to 2.5 mg/L (mean 1.48 ± 0.79 mg/L).…”

Scientific Opinion on Flavouring Group Evaluation 9, Revision 5 (FGE.09Rev5): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivat

“…Workers employed in a shoe factory were exposed to small amounts of cyclohexane in the air. Cyclohexanol and cyclohexanone were found in the urine of these workers, indicating that the same metabolic pathways are also found in humans (Governa et al, 1987).…”