782 6. ARSENICALS 



Changes in Distribution with Time 



Once bound in the tissues, the arsenicals are released rather slowly 

 as one would expect, and several instances of the arsenical remaining after 

 2-3 weeks, or longer, have been reported (e. g., Magnuson and Eaulston, 

 1941; Lanz et al., 1950). In most of the studies included in Table 6-18, 

 values are also reported for shorter or longer intervals than those given, 

 so that changes in the distribution can be observed. If one plots the tissue 

 concentrations with time, one obtains a variety of curves reaching their 

 maxima at different times and falling at different rates. The initial distri- 

 bution to some extent depends on the blood flow to the tissues, while the 

 final distribution depends more on the relative permeabilities and binding 

 powers of the various tissues. The original papers should be consulted for 

 these complex results and special attention should be given to the compar- 

 ative study of four arsenicals by Chance et al. (1945), where marked differ- 

 ences between the arsenicals may be seen at the 1- and 24-hr determinations. 



Distribution studies are not as simple as many believe and there are un- 

 fortunately complex problems which have not been solved. In much of the 

 work, blood was not thoroughly removed from the tissues before analysis 

 and there is variable contamination from this source, which may be quite 

 high in tissues like the spleen. We often do not know the form of the arsenic 

 in the tissues, since it is determined either chemically or by radioactivity 

 counting. It is not impossible that some of the compounds are metabolized 

 and the arsenic occurs in other combinations, so that in studies of the organic 

 arsenicals particularly, e. g. oxophenarsine, one should not conclude that 

 the findings represent oxophenarsine itself in the tissues. Recent advance 

 in the chemical analysis of the arsenicals may soon enable this problem to 

 be answered. 



Excretion of the Arsenicals 



Arsenicals are excreted at different rates, depending greatly on the valence 

 state; the pentavalent arsenicals are usually excreted rapidly by the kid- 

 ney, since they do not bind readily to the tissues, whereas the trivalent 

 arsenicals become rapidly bound and are excreted only as fast as they are 

 released. A fairly high concentration of arsenical in the bile has often been 

 noted and probably accounts for the relatively high fecal levels and in some 

 instances the large fraction excreted in the feces. For example, when oxo- 

 phenarsine is given intravenously over 4 days to dogs, 26.8% occurs in 

 the urine, 34.5% in the feces, 26.7% in the tissues, and 12.8% is unaccounted 

 for (Magnuson and Raulston, 1941). Monkeys given carbarsone oxide excrete 

 large amounts in the bile and feces (Anderson et al., 1947). Very similar 

 results are seen with dichlorophenarsine in man where, over a 6-day period 

 following a single intravenous injection, urinary excretion is 18.6-20.8% 

 and fecal excretion 21.6-43.4% (Henning and Kampmeier, 1943). In the 



