Abstract
Background2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors.MethodsMorning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis.ResultsCases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age.ConclusionsSignificantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.
Highlights
Polyneuropathy is a common disorder of the peripheral nervous system in middle and late adulthood
Alcohol, and general anaesthesia were associated with lower excretion in men, but for occupational exposure to nitrous oxide in women a higher excretion was seen
The choice of “total” or “free” 2,5-HD as index of exposure is under debate and still controversial [26]. To our knowledge this is the first study investigating urinary 2,5-HD levels in cases with cryptogenic polyneuropathy compared to the general population
Summary
Polyneuropathy is a common disorder of the peripheral nervous system in middle and late adulthood. The aetiology is sometimes not clear, even after thorough medical examination, and the polyneuropathy is referred to as cryptogenic. Studies suggest a role of occupational exposures in the aetiology of cryptogenic polyneuropathy. The organic solvents methyl-n-buthyl ketone (MBK) and n-hexane are well known to cause polyneuropathy through the toxic metabolite 2,5-hexanedione (2,5-HD) [3,4]. MBK has even greater neurotoxic potential than nhexane and another organic solvent, methylethyl-ketone (MEK) is known to potentiate the neurotoxic effect [5,6]. MBK and n-hexane are used for adhesives or extraction. N-hexane was used in the extraction of vegetable oil for e.g. margarine production with a threshold limit value of 1 mg/kg applied by the National Food Agency in Sweden. There are various routes of n-hexane exposure to the human body (inhalation, dermal and oral) and it is difficult to estimate the total exposure in the environment, because both occupational and life style factors can contribute
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