2-hexanone toxicity

Toxicity of n-Hexane Metabolites. Since n-hexanc is metabolized in the body, exposure also occurs to metabolites. The neurotoxicity of w-hexane is believed to ultimately result from the effects of one of these metabolites, 2,5-hexanedione, on peripheral nerves (see Section 2.4, Mechanisms of Action). One potential metabolite, 2-hexanone, has also caused neurotoxicity in humans (Allen et al. 1975). The other metabolites of -hexane (see Figure 2-3) can also produce neurotoxicity in rats via their subsequent metabolism to 2,5-hexanedione (Krasavage et al. 1980). No information was located regarding other mechanisms of toxicity for these metabolites. 

ATSDR. 1991. Toxicological profile for 2-hexanone. Agency for Toxic Substances and Disease Registry. Public Health Service. U.S. Department of Health and Human Services. Atlanta, GA. TP-91/18. 

A reduction in total white blood cell counts to 60% of control values (p<0.05), but no changes in differential white cell counts or evidence of bone marrow damage, was found in rats intermittently exposed to 700 ppm 2-hexanone after 8 weeks during an 11-week study (Katz et al. 1980). These findings, although inconclusive, suggest that immunological effects may warrant some consideration in future assessments of the potential toxicity of inhalation exposure to 2-hexanone. 

Severe neurotoxicity was reported in rats as a result of 7 days of continuous inhalation exposure to 225 ppm 2-hexanone (Couri et al. 1977). However, no data for this toxic effect were given in the study. Paralysis was observed in rats exposed to 225 ppm 2-hexanone (purity not stated) for 9.5 weeks or to 400 ppm for 6 weeks (Saida et al. 1976). Inpouchings of the myelin sheath of the... 

Branchflower and Pohl (1981) postulated that this depletion might be associated with the potentiation of toxic effects from chloroform (CHCP) when coadministered with 2- hexanone, since depletion of hepatic GSH could allow more phosgene (COCI2) (the toxic oxidation product of chloroform) to react with sensitive tissue components. 

As discussed in Section 2.2, estimates of levels of exposure to 2-hexanone posing minimal risk to humans (MRLs) were to have been made, where data were believed reliable, for the most sensitive noncancer effect for each route and exposure duration. Flowever, no MRLs could be derived for 2-hexanone. No data were located on effects of acute-duration or chronic-duration inhalation exposure to 2- hexanone in humans or animals. Available information concerning effects of intermediate-duration inhalation exposure in humans and animals identifies neurological effects as the most sensitive indicator of toxicity, but this information does not reliably identify the threshold for this effect. Therefore, no inhalation MRLs were derived. Available information on acute-duration oral exposure in animals does not identify the most sensitive effect, and while available information on intermediate-duration oral exposure to 2-hexanone in animals suggests that neurotoxicity may be the most sensitive effect, data do not reliably identify the threshold for neurotoxicity. No information was located on effects of chronic-duration exposure to 2-hexanone in humans or animals. Therefore, no oral MRLs were derived. Acute-duration, intermediate-duration, and chronic-duration dermal MRLs were not derived for 2-hexanone due to the lack of an appropriate methodology for the development of dermal MRLs. 

These results suggest that persons living or working in the vicinity of hazardous waste sites or workers who are exposed to 2-hexanone in combination with any of the potentially toxic substances discussed above may be at special risk for the effects of exposure to the combination of chemicals. 

No population has been identified which is unusually susceptible to toxic effects resulting from 2-hexanone exposure. 

This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to 2-hexanone. However, because some of the treatments discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to 2-hexanone. When specific exposures have occurred, poison control centers and medical toxicologists should be consulted for medical advice. 

The half-life of 2-hexanone and its metabolites in blood plasma has not been established however, elimination from the body does appear to occur in less than 24 hours following both inhalation and ingestion exposures (DiVincenzo et al. 1977, 1978). 2-Hexanone is not known to accumulate over time in any tissues in the body (see section 2.3.4). While elimination enhancement through stimulation of metabolism of 2-hexanone may reduce some forms of toxicity, if used within the short time that 2-hexanone is retained in the body, there is the risk that these same metabolic reactions may form reactive metabolites such as 2,5-hexanedione. Furthermore, concurrent exposures to other substances may also occur for which stimulation of these same metabolic pathways is contraindicated. Therefore, the benefit of stimulating specific metabolic pathways to enhance 2-hexanone elimination is unclear and should be studied further. 

The major toxic effect of exposure to 2-hexanone is neuropathy. Neuropathy can be caused by both 2-hexanone and its metabolite 2,5-hexanedione. A reduction of the neuropathy caused by exposure to 2-hexanone could theoretically be achieved through shunting of metabolism to less toxic metabolites. However, as discussed above, the toxicity of those other metabolites, and the effect of the treatment on metabolism of other potential toxicants, would have to be clearly assessed. 

No research on the toxicity or toxicokinetics of 2-hexanone is known to be in progress. 

Couri D, Milks M. 1982. Toxicity and metabolism of the neurotoxic hexacarbons n-hexane, 2-hexanone, and 2,5-hexanedione. Ann Rev Pharmacol Toxicol 22 145-166. 

The metabolites of n-hexane injected in guinea pigs were reported as 2,5- hexane-dione and 5-hydroxy-2-hexanone, which are also metabolites of methyl butyl ketone (DiVincenzo et al. 1976). Thus methyl butyl ketone and n- hexane should have similar toxicities. The neurotoxic metabolite, 2,5-hexanedione, however, is produced considerably less in n-hexane. However, in the case of hexane, the neurotoxic metabolite 2,5-hexanedione is produced to a much lesser extent. Continuous exposure to 250 ppm n-hexane produced neurotoxic effects in... 

Methyl fhbutyl ketone (MBK, 2-hexanone [CAS 591-78-6]) Vapors Irritating to eyes and respiratory tract at high levels. A CNS depressant at high doses. Causes peripheral neuorpathy by a mechanism thought to be the same as that of n-hexane. Well absorbed by all routes. Causes testicular toxicity In animal studies. 

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