Scientific Proceedings. 



(241) 71 



44 (136). " The toxicity of indol " : A. N. RICHARDS and JOHN 

 HOWLAND. 



Previous observers have shown the comparatively slight tox- 

 icity of indol, large amounts having been given to dogs with no 

 resulting symptoms. 



A series of experiments on rats, guinea pigs and rabbits have 

 shown that if the capacity of the cells of utilizing oxygen is dimin- 

 ished, as by potassium cyanid, or chloroform, the intensity and 

 duration of symptoms following the injection of definite doses of 

 either indol or phenol are increased. 



Experiments on dogs have shown that if potassium cyanid is 

 given together with indol (0.25-0.5 gm.) by subcutaneous injection, 

 a series of symptoms results which ends after a period of days with 

 the death of the animal. The symptoms consist of stupor and delir- 

 ium, loss of power over limbs, exaggerated reflexes with spasticity 

 of hind limbs, hypersensitiveness in the lumbar region, especially 

 the tail, loss of sight, constant nausea, feces diminished in amount 

 and bloody, and emaciation. Autopsy showed marked congestion 

 of the mucosa of the duodenum, ileum, and colon, blood in the 

 intestinal contents, degenerative changes in the liver and intestinal 

 mucosa, excessive cerebrospinal fluid, and softening of the brain- 

 tissue. 



Comparable results have been obtained when prolonged chloro- 

 form anesthesia or prolonged asphyxia has been substituted for the 

 cyanid. 



In one experiment an intestinal fistula of the Thiry-Vella type 

 was established in a dog and complete recovery from the operation 

 allowed. On poisoning with potassium cyanid and indol, the latter 

 could not be detected in the urine but was found in the contents of 

 the isolated intestinal loop. Urinary examinations in the various 

 experiments showed that diminished oxidation lessens the intensity 

 and prolongs the duration of the indican reaction in the urine. I ; ;^ 



The experiments were made as a part of a study of the etiologic 

 factors in recurrent vomiting in children. At the beginning of 

 these seizures there are signs of diminished oxidation (increased 

 elimination of uric acid, neutral sulfur, lactic acid, acetone bodies) 

 and an abnormally intense indican reaction. It is believed that 

 failure to oxidize completely substances of the type of indol, may 



