Critical review of the toxicity of methyl n-butyl ketone: risk from occupational exposure.

Methyl n-butyl ketone (MBK) was considered rather harmless until an outbreak of peripheral neuropathy occurred in 1973 among workers exposed to MBK. MBK easily penetrates the skin; pulmonary retention is approximately 80-85% in man. Distribution is widespread with highest levels in blood and liver; MBK also reaches the fetal tissues. MBK metabolism probably depends on the route of exposure, and is very similar to that of n-hexane. The critical organ is the nervous system. These effects find expression as peripheral neuropathy, with potential for serious effects of the central nervous system. From the viewpoint of neurotoxicity, 2,5-hexanedione is the most important metabolite. The neurotoxicity is potentiated by several compounds, while MBK itself potentiates the toxicity of other chemicals. From animal experiments, a no-adverse-effect level (NAEL) could not be established. Peripheral neuropathy may develop in workers exposed to only a few ppm of MBK. The difference in the Occupational Exposure Limits for MBK and n-hexane, as established by several organizations, is questioned in view of the neurotoxic effects of these substances.