QUANTITATIVE PATHOLOGICAL STUDIES WITH ARSENIC COMPOUNDS I. THE INFLUENCE OF FASTING AND VARIOUS DIETS ON ARSPHENAMINE POISONING AND THE COMPARATIVE TOXICITY OF ARSPHENAMINE, NEOARSPHENAMINE AND PARA-OXY-META-AMINO-PHENYL-ARSENOXIDE

¹ From the Division of Pharmacology, Hygienic Laboratory, United States Public Health Service

The pathology of experimental arsphenamine, neoarsphenamine and p-oxy-m-amino-phenyl-arsenoxide poisoning is described on a quantitative basis.

Starved animals and those fed sugar alone in the days preceding the intravenous administration of sodium arsphenamine are very susceptible to arsphenamine poisoning. A maximal kidney injury is to be expected.

A diet of white bread, rolled oats and whole milk greatly increases the resistance and exerts a marked protective action against the kidney injury.

A method is proposed for the standardization of the rat for the biological testing of drugs. Accurate diet control in the days preceding the administration of the drug is very important. Animals unfit for the test may be detected by following the weight curves.

Neoarsphenamine is much more toxic to the rat and dog kidney than sodium arsphenamine. The kidney injury produced by arsphenamine is transient while that caused by neoarsphenamine may be permanent.

Para-oxy-meta-amino-phenyl-arsenoxide has been found to be five times more toxic to the rat kidney than neoarsphenamine when compared on an arsenic equivalent basis and seven and one-half times more toxic than sodium arsphenamine.

Administration of mercury in doses corresponding to therapeutic doses in man apparently does not materially increase the severity of the renal injury produced by arsphenamine.

Lethal doses of sodium arsphenamine administered intravenously to dogs on a diet of medium fat beef may be followed by jaundice and liver necrosis in some instances comparable with acute yellow atrophy.

Arsphenamine and neoarsphenamine react differently in the animal organism and should not be considered as one and the same compound.

Good preparations of arsphenamine and neoarsphenamine when administered in doses corresponding to those ordinarily used clinically are harmless to the normal animal organism.

The detailed report will appear in the near future as a Hygienic Laboratory Bulletin.