HYDROCARBONS 341 



jugatcd with sulfuric acid or glucuronic acid, followed by their excretion in 

 the urine. Phenol or catechol can be oxidized before conjugation to 

 trans-trans-muconic acid. Presumably, the latter compound is mainly 

 oxidized to carbon dioxide and water; acetone bodies are possible inter- 

 mediates. Some benzene is combined directly with mercapturic acid to 

 form the detoxieation product, phenylmercapturic acid. The metabolic 

 fate of a single oral dose of C '"'-labeled benzene was reported by Parke 

 and Williams '^^ as indicated in Table 2. 



(b) Toluene and Other Methyl-Substituted Benzenes. When one intro- 

 duces a methyl group on the benzene nucleus, the compound is readily 

 oxidized on the aliphatic side-chain. As early as 1867, Schultzen and 

 Xaun}^!'^^ reported that the methyl substituent was oxidized to a car- 

 boxyl group in the animal body. The benzoic acid so formed is then ex- 

 creted as hippuric acid. Toluene, CeHs • CH3, behaves in the following way: 



CeHsCHs > CeHoCOOH > CeHjCONH-CHoCOOH 



Toluene Benzoic acid Hippuric acid 



The Detoxieation of Toluene in the Animal Body 



According to Epstein and Braunstein,-^^ up to 70% of the administered 

 toluene was found to be converted to benzoic acid. Ivnoop and Gehrke^^^ 

 were able to isolate 12 g. of hippuric acid from the urine after 7 g. of 

 toluene had been administered to a dog; this figure constitutes an 80 to 

 90% conversion of toluene. The fate of the balance of the toluene is not 

 certain. Presumably it is not converted to phenols, as no increased ex- 

 cretion of ethereal sulfate occurs. Possibly it is changed to benzoic acid 

 and is excreted in conjugation with glucuronic acid. 



In the case of benzene derivatives having more than one methyl group 

 attached to the ring, only one of the methyl groups is oxidized; in some 

 cases, a hydroxyl group is also introduced into the ring. Some of the reac- 

 tions proved experimentally are the followmg: 



CONHCH2COOH 



IxiJCHs \^CH3 ^CH3 



wi-Xylene »t-Toluic acid m-Toluric acid 



The Metabolism of ?«-Xylene in the Dog and Rabbit'^*--^ 



"8 I. S. Epstein and A. E. Braunstein, Biochem. Z., 235, 328-3.33 (1931 ). 

 "9 F. Knoop and M. Gehrke, Z. physiol. Chew., I46, 63-71 (1925). 

 230 E. Fihppi, Arch.farmacol. sper., 18, 178-192, 193-211 (1914). 



