Comparative neurotoxicity and metabolism of ethyl n-butyl ketone and methyl n-butyl ketone in rats
| Autor: | C.J. Terhaar, John L. O'Donoghue, Gary V. Katz, G.D. DiVincenzo |
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| Rok vydání: | 1980 |
| Předmět: |
Male
Ketone Time Factors Stereochemistry Oxidative phosphorylation Toxicology Methyl n-Butyl Ketone Medicinal chemistry Ethyl-n-butyl ketone medicine Animals Biotransformation Pharmacology chemistry.chemical_classification Inhalation Air Body Weight Neurotoxicity Metabolism Ketones medicine.disease Rats chemistry Argument (complex analysis) Nervous System Diseases |
| Zdroj: | Toxicology and applied pharmacology. 52(1) |
| ISSN: | 0041-008X |
| Popis: | The six-carbon compounds methyl n -butyl ketone (MnBK) and n -hexane are metabolized by oxidation of their subterminal carbons through a series of steps leading to the production of 2,5-hexanedione (2,5Hxdn). Each oxidative step increases the neurotoxic potential so that 2,5Hxdn is the most active compound in the metabolic series. The most likely seven-carbon compound commercially available that would produce a metabolic analog to 2,5Hxdn is ethyl n -butyl ketone (EBK). A study was conducted to determine the neurotoxicity of EBK and to identify its major metabolites. Rats were exposed to 700 ppm MnBK by inhalation for 11 weeks or EBK for 24 weeks, twice the exposure period needed to produce a severe, clinically evident neuropathy with MnBK. No clinical or neuropathological evidence of neurotoxicity was evident after EBK exposure. These findings appear to be due to the low serum concentrations of 2,5-heptanedione (6.8 ± 4.0 μg/ml) formed from EBK in comparison to the much higher concentrations of 2,5Hxdn (133.2 ± 36.7 μg/ml) formed from MnBK. This argument is strengthened by the fact that in a companion study, 2,5-heptanedione administered to rats 5 days per week by gavage in 1000 and 2000 mg/kg/day doses was found to produce the same type of neurotoxicity as seen with 2,5-Hxdn. |
| Databáze: | OpenAIRE |
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