EFFECTS OBSERVED IN THE WHOLE ANIMAL 725 



of the substance to penetrate into cells is modified and consequently the 

 toxic potency is changed. Of course, other factors must also contribute 

 — e. g., the rate of metabolism or inactivation of the arsenicals, the rate 

 of excretion, the binding to metabolically inert material — but these must 

 play a minor role. The fact that substitution of phenylarsenoxide generally 

 reduces the toxicity might be expected on the basis that bulky or charged 

 groups would reduce penetration. Further discussion of structure-activity 

 relationships will be found in the section on the parasiticidal properties 

 of the arsenicals (page 739). 



Effects of Subtoxic Doses 



No account of the actions of the arsenicals would be complete without 

 at least brief mention of the responses attributed to the administration 

 of low doses. Arsenic has been used in veterinary medicine since at least 

 the fifteenth century, not only in the treatment of various diseases, but 

 also to make the animals strong and healthy. During the last century 

 numerous reports appeared claiming that the chronic feeding of small 

 doses of various preparations of arsenic often increases growth, appetite, 

 and activity of animals, corrects anemic conditions, and improves the coat 

 and general appearance, and for these reasons arsenic was classed as a tonic. 

 It is therefore not surprising that it was used by man for cosmetic purposes, 

 especially for making the skin soft, the eyes bright, the hair lustrous, and 

 the bust larger, and occasionally to increase the sexual powers. Indeed, in 

 Austria and Germany preparations containing arsenic, called Busenpillen, 

 were at one time commonly available. One of the most famous was 

 the Pilulae Asiaticae, which contained arsenious acid, yeast extract, black 

 pepper, and glycerol. Each pill contained 1 mg arsenious acid; it was advised 

 that the largest single dose be 5 mg and the largest daily dose 10 mg arsen- 

 ious acid. Groups of arsenic eaters have existed for centuries in certain moun- 

 tainous regions of Austria, and it is used by them to increase strength, to 

 ease respiration at the higher altitudes, and to prevent fatigue while hunt- 

 ing. Arsenical preparations have also been used as pubic depilatories by 

 Mohammedan peoples. It is not known how much toxicity has resulted 

 from such uses as these, nor is it known if there is a real basis for the 

 beliefs in the efficacy of arsenic as a tonic or growth stimulator, since most 

 of the early studies were poorly done and uncontrolled.* Sollmann (1921) 

 gave rats 0.00005-0.005 mg/kg/day for 9-24 weeks and could detect no 

 beneficial effects, only decreased appetite and weight being noted, but 

 Von Tangl (1942) claimed some stimulatory effect of cuprisulfarsenite 



* Arsanilic acid is marketed as a poultry growth stimulant under the name Pro- 

 Gen by Abbott Laboratories and apparently its effectiveness has in this instance 

 been demonstrated. 



