Further studies on ketone neurotoxicity and interactions

O’Donoghue, John L.; Krasavage, Walter J.; DiVincenzo, G.D.; Katz, Gary V.

doi:10.1016/0041-008x(84)90304-1

Cited by 42 publications

(13 citation statements)

References 13 publications

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“…Robertson et al (1989) reported that pretreatment of MEK with hexane increased the concentration of 2,5-HD found in serum and the sciatic nerve. When ethyl n-butyl ketone, another c-diketone that can induce peripheral neuropathy, was given together with MEK, the 2,5-HD concentrations measured in urine and serum increased (O'Donoghue et al 1984). Conversely, Iwata et al (1983Iwata et al ( , 1984 reported that coexposure to n-hexane and MEK decreased the concentration and AUC of 2,5-HD in serum (within 16 h) and urine.…”

Section: Discussionmentioning

confidence: 87%

Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

Zhao¹,

Misumi²,

Yasui³

et al. 1998

International Archives of Occupational and Environmental Health

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Section: Discussionmentioning

confidence: 87%

Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

Zhao¹,

Misumi²,

Yasui³

et al. 1998

International Archives of Occupational and Environmental Health

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“…The highest dose-group (approaching the LD 50 value in rats = 2760 mg/kg bw) was the only one developing treatment-related neuropathologic lesions of typical "giant-axonal" type. No neuropathology was observed in the lower dose groups (O'Donoghue et al, 1984). This study determined that 3-heptanone has a low neurotoxic potential; however when its intake was combined with methyl ethyl ketone, neurotoxic effects were potentiated, by stimulating 3-heptanone metabolism to 2,5heptandione, a neurotoxic gamma-diketone (O'Donoghue et al, 1984).…”

Section: Gamma-diketone Formationmentioning

confidence: 84%

Flavouring Group Evaluation 7, Revision 3 (FGE.07Rev3): 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

2010

EFS2

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“…The highest dose-group (approaching the LD 50 value in rats = 2760 mg/kg bw) was the only one developing treatment-related neuropathologic lesions of typical "giant-axonal" type. No neuropathology was observed in the lower dose groups (O'Donoghue et al, 1984). This study determined that 3-heptanone has a low neurotoxic potential; however when its intake was combined with methyl ethyl ketone, neurotoxic effects were potentiated, by stimulating 3-heptanone metabolism to 2,5-heptandione, a neurotoxic gamma-diketone (O'Donoghue et al, 1984).…”

Section: Gamma-diketone Formationmentioning

confidence: 86%

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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Further studies on ketone neurotoxicity and interactions

Cited by 42 publications

References 13 publications

Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

Effects of methyl ethyl ketone, acetone, or toluene coadministration on 2,5-hexanedione concentration in the sciatic nerve, serum, and urine of rats

Flavouring Group Evaluation 7, Revision 3 (FGE.07Rev3): Saturated and unsaturated aliphatic secondary alcohols, ketones and esters of secondary alcohols and saturated linear or branched‐chain carboxylic acids from chemical group 5

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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