A polyneuropathy affecting a large number of workers was recently observed at a plant producing plastic-coated and color-printed fabrics. Epidemiological data suggested strongly that methyl N-butyl ketone (MBK) was responsible for the outbreak. This hypothesis is now supported by the development of a peripheral neuropathy in chickens, rats, and cats exposed to MBK at atmospheric concentrations of 200 to 600 parts per million, 24 hours per day, 7 days per week. Although the animals were exposed continuously and the affected workers were exposed intermittently, the averages of the total number of hours of exposure for development of the peripheral neutropathy in the animals and workers were remarkably close.

Peripheral neuropathies caused by exposures to the industrial solvents n-hexane and MBK exhibit strinkingly similar characteristics. In in vivo studies, the metabolites of MBK and n-hexane identified in blood and urine of guinea pigs were 2-hexanol (partly as glucuronide in urine); and 2,5-hexanedione which was detected only in MBK treated groups. Phenobarbital pretreatment increased 2-hexanol urinary excretion in both solvent treatment groups. In in vitro studies, hepatic reduction of MBK required the cytosol fraction to form 2-hexanol; whereas the oxidation of MBK and n-hexane required the microsomal fraction to form 2,5-hexanedione and 2-hexanol, respectively. The in vivo and in vitro biotransformation of MBK and n-hexane to a common metabolite (2-hexanol) suggests that the neurotoxic action of these solvents may be metabolite related.

MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.

No abstract

No abstract