Abstract
The drug metabolising enzyme endowment of the higher vertebrates has a blind spot. There is no general capacity for dehalogenating polybrominated or polychlorinated aromatic compounds. Exposure to such compounds where metabolic transformation is blocked by the particular isomeric disposition of Cl- or Br-substituents, leads to their persistence and accumulation in the tissues.
The attendant health hazards of such accumulation in the tissues for various vertebrate species are now recognised, especially since the localised accidental overexposure of cattle to polybrominated biphenyls in the U.S.A., and of humans to polychlorinated biphenyls and dioxin in Japan and Italy, respectively, changed the outlook even of those not directly affected.
These sentinel events served as warnings of the long-term dangers of ambient chemicals that are inadvertently bioconcentrated as the world's ecosystem becomes increasingly contaminated with such synthetic polyhalogenated residues, which unlike the naturally occurring polyiodinated aromatic compounds related to the thyroid hormones, are resistant to biodegradation.
The females of the higher vertebrates can more readily reduce their body burdens of the unmetabolisable lipophilic polyhalogenated compounds at the expense of the next generation, by sharing the burden with their progeny via the milk or their clutch of eggs.
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Allen, J.R., 1975. Federation Proc., 34: 1675–1679.
Ando, M., 1978. Arch. Toxicol., 41: 179–186.
Barr, M., Keller, C.A., Rogan, W.J., and Kline, J.R., 1979. Ann. N.Y. Acad. Sci., 320: 458–472.
Bickel, M.H., 1978. In: J.R. Fouts and I. Gut (Editors), Industrial and Environmental Xenobiotics. Excerpta Medica, Amsterdam, p. 156–160.
Bickel, M.H. and Muehlebach, S., 1980. Drug. Metab. Revs., 11: 149–190.
Bowes, G.W., Mulvihill, M.J., Simoneit, B.R.T., Burlingame, A.L. and Risebrough, W.J., 1975. Nature, 256: 305–307.
Brandt, I., Högman, P.-G., Larsson, Y. and Olsson, S., 1978. Acta Vet. Scand., 19: 368–376.
Brilliant, L.B., Van Amburg, G., Isbister, J., Humphrey, H., Wilcox, K., Eyster, J., Bloomer, A.W. and Price, H., 1978. Lancet, 2: 643–646.
Brodie, B.B. and Maickel, R.P., 1962. In: B.B. Brodie and E.G. Erdös (Editors), Proceedings of the First International Pharmacology Meeting, Vol. 6, Pergamon Press, London, p. 299–324.
Brodie, B.B., Maickel, R.P. and Jondorf, W.R., 1958. Federation Proc., 17: 1163–1174.
Carter, L.J., 1976. Science, 192: 240–243.
Chopra, I.J., Solomon, D.H., Chopra, U., Wu, S.Y., Fisher, D.A. and Nakamura, Y., 1978. Recent Progr. Hormone Res., 34: 521–556.
DeMatteis, F., Prior, B.E. and Rimington, C., 1961. Nature, 191: 363–366.
Dunckel, A.E., 1975. J. Amer. Vet. Med. Assoc., 167: 838–841.
Environmental Protection Agency, National Conference on Polychlorinated Biohenyls, Conference Proceedings EPA-560/6-75-004, Washington D.C., 1976.
Fishbein, L., 1974. Annu. Rev. Pharmacol., 14: 139–156.
Goldstein, J.A., Hass, J.R., Linko, P., and Harvan, D.J., 1978. Drug Metab. Disp., 6: 258–264.
Hay, A., 1976. Nature, 262: 636–638.
Henschler, D., 1977. In: W. Forth, D. Henschler and W. Rummel (Editors), Allgemeine und Spezielle Pharmakologie und Toxikologie, 2nd edition, Bibliographisches Institut Wissenschaftsverlag, Mannheim, p. 572–642.
Hoerschelmann, H., Polzhofer, K., Figge, K. and Ballschmiter, K., 1979. Environ. Pollut., 13: 247–269.
Hutzinger, O., Nash, D.M., Safe, S., DeFreitas, A.S.W., Norstrom, R.J., Wildish, D.J. and Zitko, V., 1972. Science, 178: 312–314.
Jackson, T.F. and Halbert, F.L., 1974. J. Amer. Vet. Med. Assoc., 165: 437–439.
Jondorf, W.R., 1979a. In: J.W. Gorrod (Editor), Drug Toxicity. Taylor and Francis, London, p. 25–50.
Jondorf, W.R., 1979b. Trends in Biochem. Sci., 4: 141–142.
Jondorf, W.R., 1981a. In: P. Jenner and B. Testa (Editors), Concepts in Drug Metabolism Part B. Marcel Dekker, New York, p. 307–376.
Jondorf, W.R., 1981b. Drug Metab. Revs., 12: 379–430.
Jondorf, W.R., Parke, D.V. and Williams, R.T., 1955. Biochem. J., 61: 512–521.
Jondorf, W.R., Parke, D.V. and Williams, R.T., 1958. Biochem. J., 69: 181–189.
Jondorf, W.R., Wyss, P.A., Mühlebach, S. and Bickel, M.H., 1982. Brit. J. Pharmacol., 75: 64P.
Koeman, J.H., Ten Noever de Brauw, M.C. and De, Vos, R.H.S., 1969. Nature, 221: 1126–1128.
Kuratsune, M., 1976. In:K. Higuchi (Editor), PCB Poisoning and Pollution.Kodansha, Tokyo, p. 9–24.
Lancet, 1977. Editorial Lancet, 2: 19–21.
Matthews, H.B. and Anderson, M.W., 1975. Drug Metab. Dispos., 3: 371–380.
Matthews, H.B., Domanski, J.J. and Guthrie, F.E., 1976. Xenobiotica, 6: 425–429.
Metcalf, R.L., 1980. Ann. Rev. Entomol., 25: 219–256.
Neal, R.A., Beatty, P.W. and Gasiewicz, T.A., 1979. Ann. N.Y. Acad. Sci., 320: 204–213.
Newton, I. and Bogan, J., 1974. Nature, 249: 582–583.
Orrenius, S., 1976. In: N.T. Kärki (Editor), Proceedings of the Sixth International Congress of Pharmacology, Vol. 6. Pergamon Press, Oxford,p. 39–52.
Pan, H.P. and Fouts, J.R. 1978. Drug Metab. Revs., 7: 1–253.
Paine, A.J., 1978. Biochem. Pharmacol., 27: 1805–1813.
Parke, D.V. and Williams, R.T., 1960. Biochem. J. 74: 5–9.
Pazderova-Vejlupkova, J., Nemcova, M., Pickova, J., Jirasek, L. and Lukas, E., 1981. Arch. Env. Health, 36: 5–11.
Peakall, D.B., 1967. Nature, 216: 505–506.
Perry, A.S. and Agosin, M., 1974. In: M. Rockstein (Editor), The Physiology of Insecta, Vol. 6, 2nd edition. Academic Press, New York, p. 3–121.
Pocchiari, F., Silano, V. and Zampieri, A., 1979. Ann. N.Y. Acad. Sci., 320: 311–320.
Poland, A., Greenlee, W.F. and Kende, A.S., 1979. Ann. N.Y. Acad. Sci., 320: 214–230.
Rappe, C., Buser, H.R. and Bosshardt, H.-P., 1979. Ann. N.Y. Acad. Sci., 320: 1–18.
Risebrough, R.W., Rieche, P., Peakall, D.B., Herman, S.G., and Kirven, M.N., 1968. Nature, 220: 1098–1102.
Roberts, D.W., 1982. J. Amer. Med. Assoc., 247: 2142.
Sleight, S.D., Mangkoewidjojo, S., Akoso, B.T. and Sanger, V.L., 1978. Environ. Health Persp., 23: 341–346.
Sweeney, G.D. and Jones, K.G., 1978. In: J.R. Fouts and I. Gut (Editors), Industrial and Environmental Xenobiotics. Excerpta Medica, Amsterdam, p. 229–231.
Taurog, A., 1974. In: M.A. Greer, and D.H. Solomon (Editors), Handbook of Physiology, Section 7, Vol. 3. Amer. Physiol. Soc., Washington, D.C., p. 101–133.
Ullrich, V., 1978. In: J.R. Fouts and I. Gut (Editors), Industrial and Environmental Xenobiotics. Excerpta Medica, Amsterdam, p. 3–8.
Urabe, H., Koda, H. and Asahi, M., 1979. Ann. N.Y. Acad. Sci., 320: 273–276.
Vodicnik, M.J. and Lech, J.J., 1980. Toxicol. Appl. Pharmacol., 54: 293–300.
Wassermann, M., Wassermann, D., Cucos, S. and Miller, H.J., 1979. Ann. N.Y. Acad. Sci., 320: 69–124.
Woff, M.S., Anderson, H.A., and Selikoff, A.J., 1982. J. Amer. Med. Assoc., 247: 2112–2116.
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Jondorf, W.R. Unmetabolisable polyhalogenated compounds: Implications for mammalian and other vertebrate species. Vet Res Commun 7, 277–283 (1983). https://doi.org/10.1007/BF02228635
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DOI: https://doi.org/10.1007/BF02228635