Abstract
The pharmacokinetics of ethylene and 1,3-butadiene were studied in male Sprague-Dawley rats by use of a closed inhalation chamber system. Both compounds showed saturable metabolism when untreated rats were used. “Linear” pharmacokinetics applied at exposure concentrations below 800 ppm ethylene and below 1,000 ppm 1,3-butadiene. A constant elimination rate, indicative of metabolic saturation, occurred at concentrations higher than 1,000 ppm ethylene or 1,500 ppm 1,3-butadiene. Pretreatment with aroclor 1254 (polychlorinated biphenyls) increased V max for both compounds. For 1,3-butadiene, no saturation of metabolic capacity was observed with exposure concentrations up to 12,000 ppm when the rats were pretreated with aroclor 1254. A comparison with previous studies on ethane and n-pentane suggested that introduction of a double bond into a saturated aliphatic hydrocarbon increased the rate of metabolism under conditions in vivo.
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References
Andersen ME (1981) Saturable metabolism and its relationship to toxicity. CRC Crit Rev Toxicol 10: 105–150
Andersen ME, Gargas ML, Jones RA, Jenkins LJ (1980) Determination of the kinetic constants for metabolism of inhaled toxicants in vivo using gas uptake measurements. Toxicol Appl Pharmacol 54: 100–116
Ashby J, Paton D, Styles JA, Greatbanks D, Wright B (1982) Synthesis of N-7-hydroxyethylguanine and O6-hydroxyethylguanine, markers for reaction of ethylene oxide (EO) with DNA. Mutat Res 103: 257–261
Bolt HM, Filser JG (1984) Olefinic hydrocarbons: a first risk estimate for ethene. Toxicol Pathol 12: 101–105
Bolt HM, Filser JG, Buchter A (1981) Inhalation pharmacokinetics based on gas uptake studies. III. A pharmacokinetic assessment of “peak concentrations” of vinyl chloride. Arch Toxicol 48: 213–228
Bolt HM, Schmiedel G, Filser JG, Rolzhäuser HP, Lieser K, Wistuba D, Schurig V (1983) Biological activation of 1,3-butadiene to vinyl oxirane by rat liver microsomes and expiration of the reactive metabolite by exposed rats. J Cancer Res Clin Oncol 106: 112–116
Calleman CJ, Ehrenberg L, Jansson B, Osterman-Golkar S, Segerbäck D, Svensson K, Wachtmeister CA (1978) Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupationally exposed to ethylene oxide. J Environ Pathol Toxicol 2: 427–442
Citti L, Gervasi PG, Turdu G, Bellucci G, Bianchini R (1984) The reaction of 3,4-epoxy-1-butene with deoxyguanosine and DNA in vitro: synthesis and characterization of the main adducts. Carcinogenesis 5: 47–52
Dunkelberg H (1982) Carcinogenicity of ethylene oxide and 1,2-propylene oxide upon intragastric administration to rats. Br J Cancer 46: 924–933
ECETOC (1982) Technical report No. 5. Toxicity of ethylene oxide and its relevance to man. European Chemical Industry Ecology & Toxicology Centre, Ave. Louise 250, Bruxelles
Filser JG, Bolt HM (1979) Pharmacokinetics of halogenated ethylenes in rats. Arch Toxicol 42: 123–136
Filser JG, Bolt HM (1981) Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models. Arch Toxicol 47: 279–292
Filser JG, Bolt HM (1983a) Exhalation of ethylene oxide by rats on exposure to ethylene. Mutat Res 120: 57–60
Filser JG, Bolt HM (1983b) Inhalation pharmacokninetics based on gas uptake studies IV. The endogenous production of volatile compounds. Arch Toxicol 52: 123–133
Filser JG, Bolt HM, Muliawan H, Kappus H (1983) Quantitative evaluation of ethane and n-pentane as indicators of lipid peroxidation in vivo. Arch Toxicol 52: 135–147
Frank H, Hintze T, Bimboes D, Remmer H (1980) Monitoring lipid peroxidation by breath analysis: Endogeneous hydrocarbons and their metabolic elimination. Toxicol Appl Pharmacol 56: 337–344
Hallier E, Filser JG, Bolt HM (1981) Inhalation pharmacokinetics based on gas uptake studies II. Pharmacokinetics of acetone in rats. Arch Toxicol 47: 293–304
IARC (1976) Monographs on the evaluation of carcinogenic risk of chemicals to man, Vol 11. International Agency for Research on Cancer, Lyon
Jones RB, Mackrodt WC (1983) Structure-genotoxicity relationship for aliphatic epoxides. Biochem Pharmacol 32: 2359–2363
Malvoisin E, Lhoest G, Poncelet F, Roberfroid M, Mercier M (1979) Identification and quantitation of 1,2-epoxybutene-3 as the primary metabolite of 1,3-butadiene. J Chromatogr 178: 419–425
Malvoisin E, Mercier M, Roberfroid M (1982) Enzymatic hydration of butadiene monoxide and its importance in the metabolism of butadiene. In: Snyder R et al. (eds) Biological Reactive Intermediates II, Part A, Plenum Publishing Co., New York, pp 437–444
Malvoisin E, Roberfroid M (1982) Hepatic microsomal metabolism of 1,3-butadiene. Xenobiotica 12: 137–144
Schmiedel G, Filser JG, Bolt HM (1983) Rat liver microsomal transformation of ethene to oxirane in vitro. Toxicology Lett 19: 293–297
Segerbäck D (1983) Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide. Chem Biol Interact 45: 139–152
Snellings WM, Weil CS, Maronpot R (1981) Ethylene oxide: two-year inhalation study on rats. Bushy Run Research Center, Pittsburgh, PA. Unpublished Report, see ECETOC (1982)
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Bolt, H.M., Filser, J.G. & Störmer, F. Inhalation pharmacokinetics based on gas uptake studies. Arch Toxicol 55, 213–218 (1984). https://doi.org/10.1007/BF00341013
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DOI: https://doi.org/10.1007/BF00341013