The metabolism of 3-chloro,- 3-bromo- and 3-iodoprpan-1,2-diol in rats and mice.
1. The metabolism of the 3-halopropan-1,2-diols (alpha-halohydrins) has been investigated in rats and mice. Apart from 3-chloropropan-1,2-diol (I), of which some 10% is excreted unchanged by both species, the compounds are completely degraded following intraperitoneal administration. 2. The alpha-halohydrins are detoxicated by conjugation with glutathione and produce two urinary metabolites, isolated and identified as S-(2,3-dihydroxypropyl)cysteine (VII) and the corresponding mercapturic acid N-acetyl-S-(2,3-dihydroxypropyl)cysteine (VIII). 3. When incubated with rat liver supernatant, the compounds do not conjugate with glutathione and their general chemical reactivity suggests that they react via a common intermediate proposed to be glycidol (2,3-epoxypropanol, IV). As the epoxide produces the same urinary metabolites as the alpha-halo-hydrins, and conjugates with glutathione either with or without liver supernatant to form the primary metabolite S-(2,3-dihydroxypropyl)glutathione (VI), glycidol is also proposed to be the reactive intermediate in vivo. 4. The role of epoxides in intermediary metabolism is discussed.
D000433:1-Propanol / Q000096:biosynthesis; D000818:Animals; D001711:Biotransformation; D001966:Bromine; D002245:Carbon Dioxide / Q000096:biosynthesis; D002250:Carbon Radioisotopes; D002713:Chlorine; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D003545:Cysteine / Q000652:urine; D004852:Epoxy Compounds; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D007455:Iodine; D008099:Liver; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D020005:Propanols; D011409:Propylene Glycols / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D014020:Tissue Extracts
D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D020005:Propanols; D011409:Propylene Glycols; D011868:Radioisotopes; D014020:Tissue Extracts; D002245:Carbon Dioxide; D002713:Chlorine; D007455:Iodine; D000433:1-Propanol; D005978:Glutathione; D003545:Cysteine; D001966:Bromine