Assessment of the contribution of chlorinated dibenzo-p-dioxins and dibenzofurans to hexachlorobenzene-induced toxicity, porphyria, changes in mixed function oxygenases, and histopathological changes

J. A. Goldstein, M. Friesen, T. M. Scotti, P. Hickman, J. R. Hass, H. Bergman

Research output: Contribution to journalArticle

Abstract

Female rats were fed 30, 100, 300, and 1000 ppm of pure and technical grades of hexachlorobenzene (HCB) for 1 week and 30, 100, and 300 ppm of each for 4 months. Technical HCB was contaminated with 200 ppm decachlorobiphenyl and 4 ppm octachlorodibenzofuran but contained no other chlorinated dibenzofurans or dibenzo-p-dioxins (<0.5 ppm). Pure HCB contained 0.5 ppm decachlorobiphenyl but no detectable amount of any chlorodibenzo-p-dioxins. Pure and technical HCB increased aryl hydrocarbon hydroxylase, aminopyrine N-demethylase, cytochrome P-450, glucuronyl transferase, and liver/body weight ratios comparably at each dose level. Neither grade of HCB shifted the peak of the CO-difference spectrum or altered the 455:430 ratios of the ethyl isocyanide difference spectra appreciably. Livers, lungs, adrenals, and hearts were evaluated histologically. Enlargement of liver cells was seen at 100 and 300 ppm HCB. Marked hypertrophy and proliferation of the lining endothelial cells of the smaller pulmonary blood vessels was observed in rats fed 100 and 300 ppm HCB. At 100 ppm, the number of affected vessels was usually greater in rats fed technical HCB than in those fed pure HCB. At 300 ppm, the pulmonary effects of pure and technical HCB were identical. The porphyria, cutaneous lesions, hyperexcitability, changes in liver enzymes, and morphological changes in the liver were identical in rats fed pure and technical HCB at all dose levels, indicating that these changes were produced by HCB, rather than chlorinated dibenzofuran or dibenzodioxin contaminants.

Original languageEnglish (US)
Pages (from-to)633-649
Number of pages17
JournalToxicology and Applied Pharmacology
Volume46
Issue number3
DOIs
StatePublished - Dec 1978

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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