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Journal of Pharmacology And Experimental Therapeutics, Vol. 102, Issue 3, 165-178, 1951
Copyright © 1951 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE MECHANISM OF ACUTE BERYLLIUM POISONING

Kenneth W. Cochran 1, Marcella M. Zerwic 1, and Kenneth P. DuBois 1

1 University of Chicago Toxicity Laboratory and the Department of Pharmacology, University of Chicago, Chicago, Illinois

1. The 30-day intraperitoneal LD50 of beryllium as beryllium chloride was 0.56 mgm./kgm. for rats and 6.3 mgm./kgm. for guinea pigs.

2. The average normal alkaline phosphatase activity of rat tissues varied from 0.39 for serum to 48.4 mgm. P/gm. of tissue/hour for duodenum and the values for guinea pig tissues varied from 0.058 for serum to 49.3 mgm. P/gm./hour for adrenal cortex. With the exception of adrenal cortex the alkaline phosphatase activity of normal guinea pig tissues was lower than the activity of corresponding rat tissues.

3. The concentration of beryllium causing 50 per cent inhibition of alkaline phosphatase activity in vitro ranged from 1.8 x 10-6 M for rat serum to 1.2 x 10-3 M for rat adrenal cortex. Guinea pig serum phosphatase was more resistant while guinea pig adrenal cortex phosphatase was more sensitive to inhibition by beryllium. Other tissues from the two species resembled each other more closely with respect to sensitivity to inhibition by beryllium in vitro.

4. Alkaline phosphatase of rat serum was markedly inhibited by beryllium in vivo. The inhibition persisted throughout the survival time after lethal doses but was reversible after sublethal doses. The phosphatase activity of kidney and duodenum was also inhibited in vivo while the activity of other tissues was not appreciably inhibited.

5. The adenosine triphosphatase activity of tissues was inhibited by beryllium in vivo but glucose-6-phosphatase and 5-nucleotidase were not inhibited by beryllium.

6. Beryllium was found to exert a strong inhibitory action on the phosphoglucomutase activity of liver and skeletal muscle both in vitro and in vivo and the inhibitory effect could be counteracted by magnesium in vitro.

7. Analyses of the livers and kidneys of beryllium-poisoned rats revealed a decrease in phosphocreatine and adenosine triphosphate and a marked increase in inorganic phosphorus. The level of glucose-1-phosphate increased while glucose-6-phosphate decreased.

Submitted on March 21, 1951






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Copyright © 1951 by the American Society for Pharmacology and Experimental Therapeutics.