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Acute Toxicity of Acrylonitrile: Effect of Diet on Tissue Nonprotein Sulfhydryl Content and Distribution of 1–¹⁴C-Acrylonitrile or Its Metabolites

Institute of Environmental Medicine New York University Medical Center 550 First Avenue New York, NY 10016

I. L. Cote

Institute of Environmental Medicine New York University Medical Center 550 First Avenue New York, NY 10016

A. E. Rogers

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA.

E. H. Silver

Department of Environmental Medicine, CMDNJ, Rutgers University Medical School, Piscataway, NJ.

S. Szabo

Department of Pathology, Peter Bent Brigham Hospital and Harvard Medical School, Boston, MA.

The influence of diet on the acute toxicity (lethality) and distribution of glutathione as measured by tissue nonprotein sulfhydryl (NPSH) concentration following acrylonitrile (ACN) treatment was studied. The tissue distribution of radiolabeled (¹⁴C) acrylonitrile or its radioactive metabolites was also determined. The diets tested were a standard laboratory rat chow; a casein-based, complete diet; and 2 diets high in saturated fat content that were either lipotrope deficient or lipotrope supplemented. The latter 2 diets were associated with decreased weight gain in the absence of ACN and increased lethality after orally administratered ACN. The increase in lethality, while most pronounced in the group fed the lipotrope-deficient, high-fat diet, was also seen in rats fed the purified control diet. The high-fat diets were associated with increases in brain and liver NPSH concentrations (mg NPSH/100 g body weight). Following oral administration of 1–¹⁴C-ACN, blood contained the highest specific activity. In terms of fraction of administered dose, liver was found to contain the highest total fraction. In the tissues measured, a majority of radioactivity appeared bound to trichloroacetic acid (TCA) insoluble components. The sequence of tissue activity (nCi ¹⁴C per g or ml) was as follows: blood > stomach > liver, duodenum, lung, kidney > brain > adrenal. While diet affected toxicity, it did not modify this general ranking.

International Journal of Toxicology, Vol. 3, No. 1, 93-102 (1984)
DOI: 10.3109/10915818409009076


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