Identification and quantitative determination of four different mercapturic acids formed from 1,3-dibromopropane and its 1,1,3,3-tetradeutero analogue by the rat

W. Onkenhout, E J Van Bergen, J H Van der Wart, G P Vos, WC Buijs, N P Vermeulen

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

1,3-Dibromopropane (1,3-DBP) was administered i.p. in doses ranging from 5.6 to 54 mg to male Wistar rats. Four different mercapturic acids, viz. N-acetyl-S-3-bromopropyl-(MA I), N-acetyl-S-3-chloropropyl-(MA II), N-acetyl-S-2-carboxyethyl-(MA III) and N-acetyl-S-3-hydroxypropyl(-1-)cysteine (MA IV) were synthesized and identified as metabolites in urine by g.l.c.-mass spectrometry. 1,1,3,3-Tetradeutero-1,3-dibromopropane was used to study the mechanism of formation of the mercapturic acids in more detail. It was found that in the formation of MA IV a reactive episulphonium ion could be involved. Gas chromatographic quantification of the mercapturic acids (mercapturic acid assay) was correlated with a spectrophotometric thioether determination of the metabolites (thioether test). At doses up to 30 mg of 1,3-DBP, excretion of mercapturic acids was virtually complete in 24 h urine and amounted to about 19% of the dose (11.3% MA I, 4.9% MA II, 2.6% MA III and 0.2% MA IV). From excretion rate curves a half-time t1/2 was calculated as being about 4.5 h. A plateau in the dose-excretion curve was observed at 1,3-DBP doses higher than 40 mg, probably caused by glutathione depletion.

Original languageEnglish
Pages (from-to)21-33
Number of pages13
JournalXenobiotica
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1986

Keywords

  • Acetylcysteine
  • Animals
  • Chromatography, Gas
  • Dose-Response Relationship, Drug
  • Gas Chromatography-Mass Spectrometry
  • In Vitro Techniques
  • Male
  • Propane
  • Rats
  • Rats, Inbred Strains
  • Sulfides
  • Time Factors
  • Journal Article

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