Metabolic pathway 5-Nonanone was expected to be
metabolized to a γ-diketone (a diketone with the second oxygen three carbons away from the first, e.g. 2,5- or 3,6-diketones). Metabolic studies confirmed the
in vivo ω-oxidation of 5-nonanone to
2,5-nonanedione and
2-hexanone. Subsequent
oxidative and
decarboxylative steps also produce
2,5-hexanedione. Besides these metabolites, 38% of the 5-nonanone dose is converted to
carbon dioxide. No unchanged 5-nonanone is detected in the urine after administration. Of these metabolites, 2,5-hexanedione is believed to be the most
neurotoxic compound. Of all the aforementioned metabolites, the toxicity is believed to be due to the metabolic transformation to this γ-diketone.
Toxicological effects In rats, the
neurotoxicity of 5-nonanone is enhanced by
methyl ethyl ketone. This suggests
induction of
microsomal oxidizing
enzymes, which results in greater production of toxic metabolites.
Chronic exposure to the compound has been shown to produce a clinical neuropathy, characterized by giant
axonal swellings filled with
neurofilaments. It also resulted in an orange/brown discoloration of the hair of the rats. Another study was done on rats to explore the enhancement of the toxicity of 5-nonanone by 5-methyl-2-octanone. The combination of these two compounds increases the neurotoxic effect of 5-nonanone approximately sixfold. When only exposed to 5-methyl-2-octanone
liver swelling was observed, indicating that metabolic activation of hepatic oxidative
enzymes may be the cause of the increase in toxicity in co-administration. ==See also==