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Journal of Pharmacology And Experimental Therapeutics, Vol. 116, Issue 4, 394-403, 1956
Copyright © 1956 by American Society for Pharmacology and Experimental Therapeutics

OBSERVATIONS ON THE TOXICITY OF A NEW UROGRAPHIC CONTRAST MEDIUM, SODIUM 3,5-DIACETAMIDO-2,4,6-TRIIODOBENZOATE (HYPAQUESODIUM) AND RELATED COMPOUNDS

James O. Hoppe 1, A. A. Larsen 1, and F. Coulston 1

1 Pharmacology, Organic Chemistry and Experimental Pathology Sections, Sterling-Winthrop Research Institute, Rensselaer, New York

Observations on the acute intravenous toxicity of a series of 3, 5-diacylamino-2,4,6-triiodobenzoic acids in mice were presented. The least toxic compound of this series was found to be sodium 3,5-diacetamido-2,4,6-triiodobenzoate, sodium diatrizoate.

The most striking property of sodium diatrizoate was its uniformly low systemic toxicity in various animal species. Acute intravenous LD50 values from 11.3 to 14 gm./kgm. were obtained in the mouse, rat, rabbit, cat and dog.

Dose-mortality curves were sharply defined in each of the animal species. At lethal dose levels, death occurred in a few minutes to 2 to 3 hours as a result of massive breakdown of the pulmonary circulation and consequent right heart failure.

Local tissue toxicity was found to be low as judged by the absence of intimal injury upon repeated intravenous injection of a 50 per cent solution of sodium diatrizoate into the marginal ear vein of the rabbit.

No obvious evidence of pharmacodynamic activity in the cat and dog was observed at intravenous doses of 0.5 to 2.0 gm./kgm.

Sodium diatrizoate was well tolerated by rats when given intravenously in five consecutive daily dosages of 0.5 and 2.0 gm./kgm. One death was observed at 4 gm./kgm. with renal tubular nephrosis occurring in five of nine rats at this dose level.

Sodium diatrizoate was well tolerated without mortality or effect on body weight in monkeys at three successive dosages of 0.5, 1.0 and 2.0 gm./kgm. No significant histologic changes were observed.

Comparative acute toxicity data on several urographic contrast media in the mouse and rat were presented.

Submitted on November 2, 1955




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Copyright © 1956 by the American Society for Pharmacology and Experimental Therapeutics.