Experimental study on the enhancement of the neurotoxicity of methyl n-butyl ketone by non-neurotoxic aliphatic monoketones.
The neurotoxicity of methyl n-butyl ketone is known to be enhanced by combination with methyl ethyl ketone. This study was conducted to clarify the potentiating effect of aliphatic monoketones on the neurotoxicity of methyl n-butyl ketone. Rats were subcutaneously injected in the back with 4 mmol/kg/day of methyl ethyl ketone, methyl n-propyl ketone, methyl n-amyl ketone, or methyl n-hexyl ketone mixed with an equimolar dose of methyl n-butyl ketone five days a week for 20 weeks. The maximum motor fibre conduction velocity and the distal latency were measured every two weeks in the tail nerves of the treated animals and controls. All the monoketones tested enhanced the neurotoxicity of methyl n-butyl ketone. Of the compounds tested, methyl n-hexyl ketone, which had the longest carbon chain, enhanced the neurotoxicity of methyl n-butyl ketone most strongly. These results suggest that the length of the carbon chain of the aliphatic monoketones combined with methyl n-butyl ketone was related to the enhancement of the neurotoxicity of the neurotoxic compound.
D000818:Animals; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004357:Drug Synergism; D007659:Ketones / Q000494:pharmacology* / Q000633:toxicity*; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology; D009420:Nervous System / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D013623:Tail / Q000294:innervation; D013997:Time Factors
D007659:Ketones; D008742:Methyl n-Butyl Ketone; D003577:Cytochrome P-450 Enzyme System