We analysed the relationship between free 2,5-hexanedione (2,5-HD) and total 2,5-HD in the urine of 87 workers exposed to n-hexane and other solvents (hexane isomers, acetone and toluene), in relation to different working conditions. The concentration of free 2,5-HD in urine of workers exposed to n-hexane was about 12% of total urinary 2,5-HD. The most significant correlation (r = 0.936) was that of total 2,5-HD in urine with environmental n-hexane and exhaled air. With equal exposure to n-hexane, the concentrations in urine of free and total 2,5-HD increased when cutaneous absorption was involved (gloves not used), during the working week and with co-exposure to acetone. An analysis of the relationship between combined exposure to acetone and urinary concentrations of the various forms of 2,5-HD suggests that acetone might influence the toxicokinetics of n-hexane, increasing the proportion of free 2,5-HD.

No abstract

Occupational exposure to n-hexane in shoe factory workers was monitored by measuring urinary 2,5-hexanedione, the major metabolite of this solvent and the probable cause of peripheral neuropathy in exposed workers. Solvent pollution was monitored in the work environments of 189 employees, of whom 123 (65%) worked in Alicante, Spain, and 66 (35%) in Veneto, Italy. 2,5-Hexanedione was measured in spot urine samples collected from workers at the end of the shift. Information on working conditions was obtained from a previous study. A significant linear correlation was found between mean environmental concentration of n-hexane and urinary concentration of 2,5-hexanedione. The variability in the correlation may have been due to the variable use of protective clothing (gloves), and to variations in exposure during the working week. In numerous workers, percutaneous absorption of n-hexane represented as much as 50% of the total absorbed dose. Urinary concentrations of 2,5-hexanedione tended to increase during the working week. Simultaneous exposure to n-hexane and toluene tended to reduce urinary excretion of 2,5-hexanedione, whereas exposure to n-hexane and methyl ethyl ketone tended to increase excretion of the metabolite.

n-Hexane neuropathy was studied in 20 workers exposed for prolonged periods to this solvent, and with urinary 2,5-hexanedione concentrations exceeding the biological exposure index recommended by the American Conference of Governmental Industrial Hygienists (5 mg/L) with a mean of 11.02 mg/L (range 5.3-24.2 mg/L). Although neurological examination did not detect significant anomalies in any of the patients, and the conduction velocity and F waves of all the nerves tested were normal, neurographic studies revealed significant differences in the amplitude of sensory nerve action potentials (SNAP) recorded from the sural (mean 14.0 microV), median (mean 17.3 microV), and ulnar (mean 7.9 microV) nerves when compared with normal values from healthy adults of the same age range, examined under identical conditions. The amplitude of the SNAP in sural and median nerves correlated significantly with the number of years worked. The notable decrease in mean amplitude of the SNAP appeared to reflect the primary neurotoxic effects of 2,5-hexanedione.

Nerve conduction blocks, defined by a significant reduction in amplitude or area of the compound muscle action potential at proximal compared with distal sites of stimulation, have been described in glue-sniffers and in workers with industrial exposure at an early stage of n-hexane neuropathy. The frequency with which this focal conduction anomaly appears is described and discussed in the case of a very homogeneous group of 10 young workers diagnosed with n-hexane polyneuropathy. Partial conduction blocks occurred in only two workers and may have been related to the intensity and duration of toxic exposure.