The Fate of Arsenic in the Body Following Treatment of Rabbits With Certain Organic Arsenicals

Abstract

VOEGTLIN and THOMPSON [1922] have suggested that the toxicity of an arsenical is governed to a large extent by its rate of excretion. Phenylarsenoxide has a high toxicity compared with those of arsenicals used in therapeutics. In an effort to determine to what extent this can be attributed to the degree to which the arsenic-containing molecule is retained in the body, and, in particular, in vital organs, rather than to any specific properties not shared by similar arsenicals, organs and exereta of rabbits were analysed following injection with phenylarsenoxide, mapharsen (m-amino-p;-hydroxyphenylarsenoxide) and with the arsonic acid corresponding to each arsenoxide. This work had to be abandoned without completing the full programme originally planned, but it is thought that the results obtained should be put on record. While further information on certain points would be desirable, the main objective has been attained.A great deal of work has been published on the fate of mapharsen in the body following intravenous injection. The distribution and excretion of arsenic following treatment of dogs with massive doses was studied by Magnuson and Raulston [1941]. Figures for the excretion of mapharsen by dogs have also been given by Gruhzit, Dixon et al. [1936]. In rats, the distribution has been described by Wright et al. [1937] and the excretion by Voegtlin and Thompson [1922]. Excretion figures for mapharsen in man have been reported by Foerster and his co-workers [1935] and by Henning and Kampmeier [1943]. All figures for the excretion of mapharsen are in agreement in suggesting that this is a fairly rapid process, at least half of the arsenic administered being cleared in a week. In man and the dog, in contrast to the rat, more arsenic was found in the freces than in the urine.In a paper received after we had ceased work on this problem, Hogan and Eagle [1944] give an account of a detailed and extensive study of the basis for the varying toxicity of arsenicals. Results are 137

Changes undergone by phenylarsenious acid and phenylarsonic acid in the animal body

“…Solutions of phenylarseJtous acid and phenylarsonic acid as their sodium salts were prepared and tested as described in an earlier paper (Chance, Crawford & Levvy, 1945). Male rabbits only were used.…”

“…If reduction of arsonic acids occurs in the body, it is reasonable to assume that oxidation of arsenious acids will also take place prior to their excretion in the urine, since arsonic acids are more rapidly excreted (Voegtlin & Thompson, 1923). From results obtained in a study of the fate of arsenic in the body following injection of rabbits with phenylarsenious acid, mapharsen (m-amino-p-hydroxyphenylarsenoxide), and the arsonic acid corresponding to each, it was postulated that the rates of excretion of the trivalent compounds were largely determined by the rates at which they were oxidized in the body to the arsonic acids (Chance, Crawford & Levvy, 1945). Since there is some evidence to suggest that the arsenobenzenes owe their therapeutic action to oxidation in the body to arsenious acids (Voegtlin & Smith, 1920b, c;Eagle, 1939;Rosenthal, 1932), information as to the fate of the latter is of interest also in connexion with the former class of compounds.…”

A Study of Arsine Poisoning

“…The contribution by arsenites freed from haemolysed erythrocytes to the general state of arsenical poisoning, which can never be regarded as insignificant, must become predominant with low concentrations of arsine. Its effectiveness will then be conditioned by the balance between the rate of absorption of the gas on the one hand and oxidation and excretion on the other [see Chance et at., 1945].…”

“…As a mnatter of interest, the total amounts of arsine in the bodies of the rabbits exposed to the gas were calculated according to the method described in a previous paper [Chance, Crawford and Levvy, 1945].…”

The quantitative separation on the micro-scale of phenylarsenious acid, phenylarsonic acid, arsenious acid and arsenic acid in simple solution and in urine

“…All evidence for this is, however, of an indirect nature (Voegtlin & Smith, 1920;Yorke & Murgatroyd, 1930; Murgatroyd, Russell & Yorke, 1934;Thuret, 1938). It has also been suggested that arsenoxides are oxidized before excretion in the urine (Chance, Crawford & Levvy, 1945). Evidence as to whether or not inorganic arsenic derivatives are formed from organic arsenicals in the body is scanty and inconclusive.…”