Characterization of the metabolites of methyl n-butyl ketone, methyl iso-butyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance

DiVincenzo, G.D.; Kaplan, C.; Dedinas, Jonas

doi:10.1016/0041-008x(76)90230-1

Cited by 230 publications

(47 citation statements)

References 9 publications

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“…Observations in humans and investigations in animals have characterized this as a distal sensorimotor neuropathy, specifically a distal axonopathy (dying-back) type (146). Another solvent, methyl n-butyl ketone, also causes a sensorimotor neuropathy, and the formation of the same toxic metabolite, 2,5-hexanedione, from both n-hexane and methyl n-butyl ketone has been firmly demonstrated (147). The pathogenesis of n-hexane neuropathy has been recently reviewed (148 (149,150).…”

Section: Styrenementioning

confidence: 99%

Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations

Costa¹

1996

Environmental Health Perspectives

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There is an increasing interest in the development and validation of biomarkers for use in biochemical/molecular epidemiological studies. Though the area of neurotoxicology has received much attention in the past several years, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review discusses several aspects of biomarker research as it relates to neurotoxic compounds and focuses on selected agents (organophosphorus insecticides, styrene, n-hexane, carbon disulfide, acrylamide), which have been the subject of a number of investigations in animals and humans. While traditional biomonitoring approaches and novel techniques (e.g., hemoglobin adducts) provide several measurements for monitoring exposure to neurotoxic chemicals, potential markers of genetic susceptibility have been seldom investigated in a neurotoxicology context. Furthermore, the complexity of the nervous system, together with the multiplicity of end points and the limited knowledge of the exact mechanism(s) of action of neurotoxicants, has led to only limited advancements in the development of biomarkers for neurotoxic effects. Significant progress in this area will depend upon an increased understanding of the cellular, biochemical, and molecular targets directly involved in neurotoxicity. Environ Health Perspect 1 04(Suppl 1): 55-67 (1996)

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Section: Styrenementioning

confidence: 99%

Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations

Costa¹

1996

Environmental Health Perspectives

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“…The concentration of 4-methyl-2-pentanol was too low for quantification. 4-Methyl-2-pentanone is metabolised by oxidation at the omega-1 carbon atom to form the hydroxylated ketone, 4-hydroxy-4-methylpentan-2-one, and to a lesser extent by reduction of the carbonyl group to form the secondary alcohol, 4-methyl-2-pentanol (DiVincenzo et al, 1976).…”

Section: Iii3 Studies On Candidate Substancesmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 11, Revision 2 (FGE.11Rev2): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

Publication¹

2011

EFS2

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“…The concentration of .183] was too low for quantification. 4-Methylpentan-2-one is metabolised by reduction of the carbonyl group to form the secondary alcohol, , and by oxidation at the omega-1 carbon atom to form the hydroxylated ketone, 4-hydroxy-4-methylpentan-2-one (DiVincenzo et al, 1976).…”

Section: Studies With Specific Substancesmentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 7, Revision 4 (FGE.07Rev4): Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched‐chain carboxylic acids from chemical group 5

Flavourings¹

2012

EFS2

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The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 49 flavouring substances in the Flavouring Group Evaluation 07, including additional five substances in this Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. Since the publication of the last revision of this FGE, the EFSA has been requested to evaluate five additional substances, 2,6-dimethylocta-1,5,7-trien-3-ol, octa-1,5-dien-3-ol, undeca-1,5-dien-3-ol, pseudo-ionone and 3,3,6-trimethylhepta-1,5-dien-4-one 02.194, 02.211, 07.198 and 07.204], which have been included in the present revision of FGE.07. None of the 49 substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that all 49 substances do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of the flavouring substances, the specifications for the materials of commerce have also been considered. For three substances 02.211 and 02.255] the stereoisomeric compositions have not been given and for one substance 02.194, 02.211, 07.198 and 07.204]. These substances have been considered with respect to genotoxicity in FGE.206 (EFSA, 2011c) and the Panel concluded that the data available ruled out the concern for genotoxicity and thus concluded that the substances can be evaluated through the Procedure.The 49 candidate substances are saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched-chain saturated carboxylic acids from chemical group 5.Twenty-five candidate substances possess one chiral centre 02.142, 02.145, 02.148, 02.177, 02.183, 02.190, 02.194 Due to the presence and the position of double bonds, 10 candidate substances can exist as geometrical isomers 02.194, 02.211, 02.255, 07.156, 07.198, 07.236, 07.239, 09.386, and 09.880]. For one of these ], the stereoisomeric composition has been specified as the E/Z mixture, but the composition of the mixture has not been given.Twenty-eight candidate substances belong to structural class I, and 21 candidate substances belong to structural class II.Forty-five of the flavouring substances in the present group of 49 flavouring substances have been reported to occur naturally in a wide range of food items.In its evaluation, the Panel as a default used the "Maximised Survey-derived Daily Intake" (MSDI) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Panel examined the information provided by the European Flavour Industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular...

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Characterization of the metabolites of methyl n-butyl ketone, methyl iso-butyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance

Cited by 230 publications

References 9 publications

Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations

Biomarker Research in Neurotoxicology: The Role of Mechanistic Studies to Bridge the Gap between the Laboratory and Epidemiological Investigations

Scientific Opinion on Flavouring Group Evaluation 11, Revision 2 (FGE.11Rev2): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

Scientific Opinion on Flavouring Group Evaluation 7, Revision 4 (FGE.07Rev4): Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched‐chain carboxylic acids from chemical group 5

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