Neurobehavioral effects of methyl N-butyl ketone and methyl n-amyl ketone in rats and monkeys: A summary of NIOSH investigations

The results from four NIOSH investigations concerning the neurobehavioral effects of methyl n-butyl ketone (MBK) and methyl n-amyl ketone (MAK) on experimental animals are summarized. The investigations were initiated following clinical reports of neurologic sequelae in humans exposed to these ketone solvents. In order to explore both acute and chronic effects of MBK and MAK, two general types of studies were conducted: neurophysiologic evaluation of monkeys and rats following chronic inhalation, and behavioral effects in rats following oral or intraperitoneal administration. Results from chronic inhalation studies after 4 months of 1000 ppm MBK exposure (all exposures: 6 hrs/day, 5 days/week) showed the following: decreased motor nerve conduction velocities (NCV) in the ulnar and sciatic-tibial nerves, reduced amplitude of evoked muscle action potentials (MAP), lengthened latency of components of the visual evoked brain potential, decreased body weight, and hindlimb drag. Decrements in sciatic-tibial NCV and MAP amplitude were found after 9 months exposure to 100 ppm MBK. In contrast, exposure to approximately 1000 ppm MAK for 9 months had no adverse effects on neurophysiologic indicators of nervous system integrity. Dose-response investigations of the effects of MBK (oral) and MAK (ip) showed for both solvents a reduction in the response rate of rats trained on a multiple schedule of reinforcement.