0000000000299156
AUTHOR
J. G. Filser
Characteristics of haloethylene-induced acetonemia in rats.
A series of halogenated ethylenes (vinyl chloride, vinylidene fluoride,cis- andtrans-1,2-dichloroethylene, perchloroethylene) induces increased acetone exhalation in rats. Exposures of differently pre-treated rats to vinylidene fluoride suggest that a metabolite of the haloethylene must be envolved in eliciting this formation of acetone. This conclusion is based on (a) dependence of acetone exhalation on the concentration of vinylidene fluoride, (b) effect of inducing agents, (c) effect of pyrazol, a metabolic inhibitor, (d) effect of cysteine, (e) effect of hypoxia and (f) the time course of acetone exhalation.
Quantitative evaluation of ethane and n-pentane as indicators of lipid peroxidation in vivo.
The use of exhalation of ethane and n-pentane in experimental animals as parameters of lipid peroxidation led to an examination of pharmacokinetics of both compounds in rats. When rats were exposed, in a closed desiccator jar chamber, to a wide range of ethane concentrations, linear elimination pharmacokinetics were observed. n-Pentane, when concentrations higher than 100 ppm were applied, displayed saturation kinetics. These were formally explained by action of two competing metabolizing pathways or enzymes. Application of preexisting models could describe exhalation of both ethane and n-pentane by untreated control rats. Stimulation of lipid peroxidation by ferrous ions or by carbon tetra…
Metabolic Activation and Pharmacokinetics in Hazard Assessment of Halogenated Ethylenes
Halogenated ethylenes play an important role in occupational and environmental medicine. Several attempts at toxicological evaluation of such compounds have been recently published (Maltoni 1977; Lee et al. 1978; Gehring et al. 1979; Kappus and Ottenwalder 1980; Henschler et al. 1980; Bolt 1980). The principal question is that of possible carcinogenicity. It is now clear that vinyl chloride (Maltoni 1977) and vinyl bromide (Bolt et al. 1979) are carcinogenic; some data also argue in favor of carcinogenicity of vinylidene chloride (Lee et al. 1978). Trichloroethylene (Henschler et al. 1980) and perchloroethylene (Bolt and Link 1980), according to present data, appear devoid of cancerogenic p…
Long-term effects of commercial and congeneric polychlorinated biphenyls on ethane production and malondialdehyde levels, indicators of in vivo lipid peroxidation
Ethane exhalation was increased in male Sprague-Dawley rats following a single intraperitoneal (IP) injection of Aroclor 1254 (500 mg/kg). In the first 2 weeks following Aroclor 1254 treatment, the increase in ethane exhalation was due to an inhibition of metabolism of endogenous ethane rather than to an increase in ethane production. In weeks 3 and 4 following Aroclor 1254 administration, metabolic clearance of ethane returned to and exceeded control levels, while ethane production increased to approximately twice the control rates (day 30). The HPLC determination of in situ hepatic malondialdehyde levels revealed a 2-fold increase in malondialdehyde content on day 30 following the Aroclor…
Increased acetone exhalation induced by metabolites of halogenated C1 and C2 compounds.
Rats were exposed, in a closed desiccator jar chamber, to concentrations of various halogenated C1 and C2 compounds at which the metabolizing capacities were saturated (Vmax conditions). Within the exposure period of 50 h concentrations of the xenobiotic and of exhaled acetone were monitored in the gas phase of the system. The quantitative extent of acetone exhalation was dependent on the individual compound examined. Acetone exhalation was stimulated in presence of vinyl chloride, vinyl bromide, vinyl fluoride, vinylidene fluoride, cis- and trans-1,2-dichloroethylene, trichloroethylene, perchloroethylene, methylene chloride, chloroform, carbon tetrachloride and 1,1,2-trichloroethane. No st…
Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).
The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 μg/kg), IP to male Sprague Dawley rats (160–180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was …
Inhalation pharmacokinetics based on gas uptake studies. IV. The endogenous production of volatile compounds.
A pharmacokinetic description of production, distribution and metabolism of endogenous volatile compounds is presented. This description uses the "gas uptake model" of a closed recirculated atmosphere in which experimental animals are exposed. As an example, the production rates of acetone, under different conditions of stimulation by xenobiotics, are calculated from published experimental data. The theoretical descriptions may serve as a basis for treating the problem of hydrocarbon exhalation in toxicological experiments with compounds eliciting lipid peroxidation.