Methylthio Metabolites of Naphthalene Excreted by the Rat

Wg, Stillwell; Oj, Bouwsma; Thenot, J. P.; Mg, Horning; Gw, Griffin; Ishikawa, Kanji; Takaku, Masaaki

doi:10.1016/b978-0-08-023768-8.52191-5

Cited by 12 publications

(13 citation statements)

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“…Any arene dioxides produced in this manner would be expected to be further metabolized to other materials, which could be mutagenic. In this connection it is of interest that naphthalene has been converted to an arene dioxide in animal liver metabolism studies (24,25). In this case both oxides are formed in the same ring.…”

Section: Resultsmentioning

confidence: 99%

Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies

1999

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The arene dioxides of five 1-substituted pyrenes have been synthesized using dimethyldioxirane. The diasteroisomeric distribution of the dioxides has been determined. X-ray crystallographic structures of the dioxides have also been obtained. These structures show that for the cis dioxides the molecular structures show a departure from planarity, the extent of which is dependent on the substituent.

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Section: Resultsmentioning

confidence: 99%

Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies

1999

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“…The epoxide of naphthalene would change any hydroxymetabolite nonenzymatically or would convert the dihydroxy metabolite through the dihydrodihydroxy metabolite by epoxide hydrolase, or the glutathione conjugate by glutathione-S-epoxide transferase. It was proposed by Stillwell et al (8) that methanethiol derived from the 2-keto-4-methylthiobutylate form by deamination of methionine was the nucleophilic agent responsible for the formation of the methylthio metabolite from the epoxide of naphthalene.…”

Section: Mechanism Of Biosynthesis Of Serial Methylsulfonyl Metabolitesmentioning

confidence: 99%

“…The serial methylsulfonyl pathway for xenobiotic metabolism has been studied in numerous laboratories for numerous compounds such as the drugs cafffeine (1), bromazepam (2), bromovalerylurea (3), acetoaminophen (4), alfoqualone (5), and 3-hydroxyxanthine (6); pesticides and fungicides, including propachlor (7), napthalene (8), (9) and PCNB (10); and pollutants such as DDE (11), PCBs (11)(12)(13), HCB (14) and monochlorodibenzo-p-dioxin (15). During the time that xenobiotic thioether derivatives were discovered, precursors including glutathione, cysteinylglycine, cysteine and N-acetylcysteine (mercapturic acid) conjugates (2,4,5,7,14) have been reported.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Biosynthesis of Methylsulfones from PCBs and Related Compounds

Mio¹,

Sumino²

1985

Environmental Health Perspectives

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, methylthio-, methylsulfinyl-and methysulfonyl metabolites of PCBs, 2,5,2',5'-tetrachlorobiphenyl, 1,3,5-trichlorobenzene and some other chlorobenzenes were identified in adipose tissues of mice, rats and guinea pigs by using GC/MS/COM systems. By means of administration of CD3-methionine, it was confirmed that the methyl group in methylthio metabolites was derived from the methionine. Moreover, after pretreatment with either esterification of urinary metabolites in guinea pigs with 1,3,5-trichlorobenzene and 1,3-dichlorobenzene or N-acetylation after esterification, it was confirmed that cysteinylglycine, cysteine, N-acetylcysteine, cysteamine, mercaptopyruvate, mercaptolactate, mercaptacetate, thiol and disulfide conjugates were detected as a serial modified derivatives of glutathione moiety.These results are summarized as a metabolic proposed pathway of halogenated aromatic compounds. Three routes in pathway correspond to oxygenation (initial route), glutathione thioether disposition (intermediate route) and sulfoxydation (final route) in connection with both reactive intermediates of epoxide and thiol. Methylation of the thiol by S-adenosylmethionine may be important in inhibiting covalent binding of reactive intermediates with biocomponents, similar to the glutathione conjugation for the detoxification of epoxide.

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“…Unconjugated metabolites accounted for 5 -20 % of the metabolites excreted, while 80 -95 % of the metabolites were excreted as acidic conjugates (Horning et al, 1980). Urinary excretion of premercapturic acids and mercapturic acids represents a major excretory pathway for naphthalene in mice and rats (Chen and Dorough, 1979;Stillwell et al, 1978;Pakenham et al, 2002). Urine was collected for 24 hours after intraperitoneal administration of 0, 1.56, 3.12, 6.25, 12.5, 25, 50, 100 and 200 mg/kg radiolabelled [ 14 C]-naphthalene dissolved in corn oil to male Sprague Dawley rats and Swiss Webster mice, four animals in each group.…”

Section: Subgroup Ivb (Naphthalene Derivatives)mentioning

confidence: 99%

Scientific Opinion on Flavouring Group Evaluation 25, Revision 2 (FGE.25Rev2): Aliphatic and aromatic hydrocarbons from chemical group 31

Flavourings¹

2011

EFSA Journal

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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 37 flavouring substances in the Flavouring Group Evaluation 25, Revision 2, using the Procedure in Commission Regulation (EC) No 1565/2000. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the ten substances 01.027, 01.028, 01.033, 01.034, 01.038, 01.039, 01.046, 01.054 and 01.057] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining 27 candidate substances 01.022, 01.023, 01.030, 01.031, 01.032, 01.035, 01.036, 01.037, 01.042, 01.043, 01.044, 01.047, 01.050, 01.051, 01.052, 01.053, 01.055, 01.056, 01.058, 01.059, 01.060, 01.064, 01.066, 01.067, 01.070 and 10.078] no appropriate NOAEL was available and additional data are required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. For five substances, the composition of the stereoisomeric mixture has to be specified further. The 37 candidate substances are aliphatic and aromatic hydrocarbons, which have been divided into eight subgroups: I) acyclic alkanes, II) acyclic alkenes, III) cyclohexene hydrocarbons, IVa) benzene hydrocarbons, IVb) napthalene hydrocarbons, IVc) diphenylmethane, V) bi-and tricyclic, nonaromatic hydrocarbons and VI) macrocyclic, non-aromatic hydrocarbons.Several of the 37 flavouring substances possess chiral centres and/or can exist as geometrical isomers. For five of the flavouring substances [FL-no: 01.021, 01.027, 01.032, 01.035 and 01.078] the stereoisomeric composition/composition of mixture has not been specified sufficiently.Thirty-one of the 37 candidate substances belongs to structural class I, two belongs to structural class II and four to structural class III according to the decision tree approach presented by Cramer et al. (1978).Thirty-three out of the 37 candidate 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 Flavouring 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 consumers of products flavoured at the use level reported by the Industry, especially in those cases where the annual production values were reported to be small. In consequence, the Panel had reservations about the data on use and use levels provided and the intake...

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Methylthio Metabolites of Naphthalene Excreted by the Rat

Cited by 12 publications

References 0 publications

Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies

Arene dioxides of substituted pyrenes: synthesis and X-ray structural studies

Mechanism of Biosynthesis of Methylsulfones from PCBs and Related Compounds

Scientific Opinion on Flavouring Group Evaluation 25, Revision 2 (FGE.25Rev2): Aliphatic and aromatic hydrocarbons from chemical group 31

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