Abstract
Mice were exposed to very small quantities of Per (0.05 and 0.1 mg Per/kg body weight per day) administered orally for 7 weeks. It was shown that Per was transported through the body by two separate mechanisms and was finally stored in the adipose tissue. On the one hand, Per reaches the interior of the membranes of red blood cells, leading to changes in the entire erythropoietic system. The membranes of the red blood cells are destroyed prematurely and its fragments are increasingly phagocytized in the spleen. The result is a high level of Per stored in the spleen. The increase in haemolysis was also demonstrated by showing an increase in LDH activity and the accumulation of haemosiderin in the macrophages in the spleen. Only 8 weeks following discontinuation of Per, these changes were reversible. On the other hand, Per is also transported with the chylomicrons. Since the lipoprotein lipase is inhibited by Per, these molecules are broken down to a lesser degree. The concentration of triglycerides (the major component of the chylomicrons) in the serum was elevated, and the chylomicrons were increasingly integrated into the adipose tissue, Per also reached this depot fat. It took as long as 16 weeks after discontinuation of Per until these changes were fully reversed and the experimental mice no longer differed from those in the control group.
Similar content being viewed by others
Abbreviations
- Per:
-
Perchloroethylene (1,1,2,2-tetrachloroethylene)
- SGPT:
-
serum glutamate-pyruvate-transaminase
- TCA:
-
trichloroacetic acid
- TCE:
-
trichloroethanol
- NAD:
-
nicotinamide adenine dinucleotide
- PBS:
-
phosphate buffered saline
- LDH:
-
lactate dehydrogenase
- LDL:
-
low density lipoproteins
- VLDL:
-
very low density lipoproteins
References
Andersen ME (1981) Saturable metabolism and its relationship to toxicity. CRC Crit Rev Toxicol 9: 105–149
Andersen ME, Gargas ML, Jones RA, Jenkins LJ (1980) Determination of the kinetic constants for metabolism of inhaled toxicans in vivo using gas uptake measurements. Toxicol Appl Pharmacol 54: 100–116
Bauer U (1981) Belastungen des Menschen durch Schadstoffe der Umwelt — Untersuchungen über leicht flüchtige organische Halogenverbindungen in Wasser, Luft, Lebensmitteln und im menschlichen Gewebe. I-IV. Zbl. Bak Hyg, I. Abt Orig B 174: 15–583
Bolt HM, Buchter A, Wolowski L, Gil DL, Bolt W (1977) Incubation of14C-trichloroethylene vapor with rat liver microsomes: Uptake of radioactivity and covalent protein binding of metabolites. Int Arch Occup Environ Health 39: 103–111
Bolt HM, Filser JG (1977) Irreversible binding of chlorinated ethylenes to macromolecules. Environ Health Perspect 21: 107–112
Brown BR, Vandam LDA (1976) Review of current advances in metabolism of inhalation anesthetics. Ann NY Acad Sci 247: 235–243
Browning E (1965) Trichloroethylene and terachloroethylene. In: Toxicity and metabolism of industrial solvents. Elsevier, Amsterdam, London
Buben JA, O'Flaherty E (1985) Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: A dose-effect study. Toxicol Appl Pharmacol 54: 105–122
Daniel JW (1963) The metabolism of36C1-labelled trichloroethylene and terachloroethylene in the rat. Biochem Pharmacol 12: 795–802
Gehring P (1968) Hepatotoxic potency of various chlorinated hydrocarbons relative to their narcotic and lethal potencies in mice. Toxicol Appl Pharmacol 13: 287–298
Gether J, Lunde G (1975) Determination of tetrachloroethylene residues in defatted meals. Lebensm Wiss u Technol 8: 183–184
Giger W, Molnar-Kubica E (1978) Tetrachloroethylene in contaminated ground and drinking waters. Bull Environ Contam Toxicol 19: 475–480
Gray E (1976) Assessment of hepatotoxic potential. Environ Health Perspect 15: 47–54
Green T, Prout MS (1985) Species differences in response to trichloroethylene. II. Biotransformation in rats and mice. Toxicol Appl Pharmacol 79: 401–411
Hartmetz G, Borneff J, Borneff M (1985) Vorkommen leichtflüchtiger Chlorkohlenwasserstoffe in Trinkwässern von Rheinland-Pfalz. Forum Städte-Hygiene 36: 316–319
Henschler D, Bonse G (1977) Metabolic activation of chlorinated ethylenes: Dependence of mutagenic effect on electrophilic reactivity of the metabolically formed epoxides. Arch Toxicol 39: 7–12
IARC (1979) Monographs on the evaluation of the carcinogenic risk of chemical to humans. IARC Lyon 20: 491–514
Ikeda M, Ohtsuji H, Imamura T, Komoike Y (1972) Urinary excretion of total trichloro-compounds, trichloroethanol, and trichloroacetic acid as a measure of exposure to trichloroethylene and tetrachloroethylene. Br J Ind Med 29: 328–333
Klein G, Gromadies B, Bürger A, Scheunert E, Rittner G (1981) Langzeitwirkungen von Schwefelkohlenwasserstoff und Halogen-kohlenwasserstoffen, besonders Perchlorethylen, auf den Lipidstoffwechsel. 7 Ges Hyg 27: 48–51
Kostner GM (1983) Apolipoproteins and lipoproteins of human plasma: Significance for health and diseases. Adv Lipid Res 20: 1–44
Lowry OH, Rosebrough NJ, Farr L, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Marth E, Stünzner D, Binder H, Möse JR (1985a) Tetrachlorethylen — Eine Studie über die Wirkung niedriger Konzentrationen von 1,1,2,2-Tetrachlorethylen (Perchlorethylen) am Organismus der Maus. I. Laborchemische Untersuchungen. Zbl Bakt Hyg, I. Abt Orig B 181: 525–540
Marth E, Stünzner D, Binder H, Möse JR (1985b) Tetrachlorethylen — Eine Studie über die Wirkung niedriger Konzentrationen von 1,1,2,2-Tetrachlorethylen (Perchlorethylen) am Organismus der Maus. II. Rückstandsuntersuchungen von Tetrachlorethylen in verschiedenen Organen und Nachweis von histologischen Veränderungen der untersuchten Organe. Zbl Bak Hyg, I. Abt Orig B 181: 541–547
Marth E, Stünzner D, Binder H, Möse JR (1986) Perchlorethylen und der Lipoproteinstoffwechsel der Maus. Hyg Med 11: 244–246
Möse JR, Wilfinger G, Zeichen R (1985) Trinkwasserverunreinigung durch Perchlorethylen. Zbl Bakt Hyg, I. Abt Orig B 181: 111–120
Munro IC (1977) Consideration in chronic toxicity testing: The chemical, the dose, the design. J Environ Pathol Toxicol 1: 183–197
National Cancer Institute (1977) Bioassay of tetrachloroethylene for possible carcinogenesis. DHEW Publ No (NIH) 77-813
Pegg DG, Zempel A, Braun WH, Watanabe PG (1979) Disposition of tetrachloro (14C)ethylene following oral and inhalation exposure in rats. Toxicol Appl Pharmacol 51: 465–474
Prout MS, Provan WM, Green T (1985) Species differences in response to trichloroethylene. I. Pharmacokinetics in rats and mice. Toxicol Appl Pharmacol 79: 389–400
Ratnoff WD, Gress RE (1980) The familial occurence of polycythemia vera: Report of a father and son, with consideration of the possible etiologic role of exposure to organic solvents, including tetrachloroethylene. Blood 56: 233–236
Reddy JK, Azarnoff DL, Hignite CE (1980) Hypolipidemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature (London) 283: 397–398
Reichert D (1983) Biological actions and interactions of tetrachloroethylene. Mutat Res 123: 411–429
Sokal R, Rohlf J (1969) Biometrics. Freeman, San Francisco, pp 235–246
Steward RD, Dodd HC (1964) Absorption of carbon tetrachloride, trichloroethylene, tetrachlorethylene, methylene chloride and 1,1,1 trichloroethane through the human skin. Am Ind Hyg Assoc J 25: 439
Zimmerli B, Zimmermann H, Müller F (1982) Perchlorethylen in Lebensmitteln. Mitt Gebiete Lebensm Hyg 73: 71–81
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marth, E. Metabolic changes following oral exposure to tetrachloroethylene in subtoxic concentrations. Arch Toxicol 60, 293–299 (1987). https://doi.org/10.1007/BF01234668
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01234668