The Oxidative Metabolism of 1-Bromopropane in the Rat

Abstract

1. The metabolism of 1-bromopropane in the rat has been re-investigated. The previously known metabolites have been isolated and confirmed as the three mercapturic acids N-acetyl-S-propyl cysteine, N-acetyl-S-propyl cysteine-S-oxide and N-acetyl-S-(2-hydroxypropyl)cysteine. 2. Three further metabolites have been isolated from the urine of rats treated with 4-bromopropane. These have been identified as 3-bromopropionic acid and the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine. 3. The metabolites of 3-bromopropanol and 3-chloropropanol in the rat have been shown to be the mercapturic acids N-acetyl-S-(3-hydroxypropyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine and the corresponding 2-carboxyethyl halide. 4. Studies with 1-bromopropane and the 3-halopropanols in vitro indicate that oxidation of C3 and C2 of 1-bromopropane occurs before conjugation of the alkyl group with glutathione. The implications of these studies are discussed in relation to the mechanism of the biosynthesis of the S-(2-hydroxyalkyl)mercapturic acid metabolites derived from the alkyl halides.

Neuro-reproductive toxicities of 1-bromopropane and 2-bromopropane

“…The presence of propylene oxide is supported by urinary N-acetyl-S-(2-hydroxypropyl)cysteine (Barnsley et al 1966;Jones and Walsh 1979) and glycidol (Ishidao et al 2002) in rats exposed to 1-bromopropane, and production of 1,2-propanediol and 2-hyroxypropylglutathione in microsomal and/or glutathione-added incubation (Tachizawa et al 1982). While it is not clear whether metabolic activation plays a role in the toxicities of these compounds, the understanding of such a process might allow us to identify the reason for the difference in toxicities of the two bromopropanes.…”

Bromide and N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing

“…Bromide ions are not further metabolized but are eliminated mainly through the kidneys (Ryan and Baumann 1999). Urinary Br (-) elevated substantially above normal (reference value = 10 mg/l) represents accumulated exposure over the previous week or two, as Br (-) is excreted slowly (Jones and Walsh 1979). Hanley et al (2006) demonstrated that urinary Br (-) is an effective biomarker of 1-BP for highly exposed foam cushion workers exposed to spray adhesives [Geometric mean (GM) = 92 ppm for sprayers; GM = 11 ppm for other jobs].…”

Development of a gas chromatographic test for the quantification of the biomarker 3-bromopropionic acid in human urine

“…A brief summary showing the proposed and generally accepted metabolic pathways of 1-BP is shown in Fig. 1, including the formation of 3-bromopropionic acid (3-BPA) metabolite [12], which is the focus of this study. The mercapturic acids, as well as 3-BPA, have been detected in urine from the rat [12].…”

“…1, including the formation of 3-bromopropionic acid (3-BPA) metabolite [12], which is the focus of this study. The mercapturic acids, as well as 3-BPA, have been detected in urine from the rat [12]. The metabolic profile has not been studied well for the human.…”

“…The metabolism of 1-BP has been studied over several years and is complex [11,12]. Two major routes of metabolism include oxidation at C2 or C3 via the cytochrome P450 monooxygenase system [13,14] and the formation of glutathione conjugates via glutathione-S-alkyltransferase.…”