The synergism of n-hexane-induced neurotoxicity by methyl isobutyl ketone following subchronic (90 days) inhalation in hens: Induction of hepatic microsomal cytochrome P-450.
Abou-Donia-MB; Lapadula-DM; Campbell-G; Timmons-PR
Toxicol Appl Pharmacol 1985 Oct; 81(1):1-16
The effect of methyl-isobutyl-ketone (108101) (MiBK) on the neurotoxicity of n-hexane (110543) was studied as an example of joint action of aliphatic solvents. A group of leghorn-hens was exposed to vapors containing 1000 parts per million (ppm) n-hexane and another group was exposed to 1000ppm MiBK each for 90 days. Four groups were exposed simultaneously to 1000ppm n-hexane in combination with 100, 250, 500, or 1000ppm MiBK. Continuous inhalation of 1000 MiBK caused leg weakness in hens after approximately 44 days. Hens exposed to 1000ppm n-hexane demonstrated mild ataxia. Exposure to mixed vapors caused ataxia after a latent period of 10 to 29 days, depending on MiBK concentration. All hens exposed to 1000ppm n-hexane and 250, 500 or 1000ppm MiBK developed all stages of ataxia and progressed to paralysis. Hens continuously exposed to 1000/100ppm n-hexane/MiBK demonstrated severe ataxia and their clinical condition did not change during the observation period. The spinal cord of one hen exposed to 1000ppm n-hexane demonstrated equivocal histologic changes in the lumbar region. The authors conclude that the nonneurotoxic chemical MiBK synergized the neurotoxic action of the weak neurotoxicant n-hexane as the coneurotoxicity coefficient for joint exposure was more than two times the additive effect of each treatment alone.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Nervous-system-disorders; Laboratory-animals; Organic-solvents; Solvent-vapors; Inhalation-studies; Ketones; Alkanes
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Neurotoxic Disorders; Neurotoxic-effects
Toxicology and Applied Pharmacology
Duke University, Durham, North Carolina