332 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



to rabbits, Porteous and Williams '^^ observed that the ratio of phenol .-total 

 polyphenols (catechol, quinol, and hydroxyquinol) was approximately 

 one;'^^ on the other hand, when phenol was administered, the above ratio 

 changed to 5 or 6. The explanation offered by Garton and Williams -'' 

 for this phenomenon is that, when phenol is administered, it is rapidly 

 conjugated with sulfate or glucuronic acid, and such conjugated compounds 

 are excreted unchanged. This would leave a relatively small proportion 

 of phenol in the free state to undergo further oxidation to the polyphenols. '^^ 



The oxidation of benzene to phenol has been shown to take place largely 

 in the liver, ^^^ both in the case of warm-blooded animals such as the cat and 

 the rabbit, and in the classical example of cold-blooded animals, namely 

 the frog. It is believed ^^* that both classes of animals Hkewise possess ex- 

 trahepatic sites where this oxidation may occur. Both free and con- 

 jugated phenols have been isolated from the livers of benzene-poisoned 

 warm-blooded animals. '^^ 



d'. Conjugation of Phenols: Phenol and the dihydroxy- and tri- 

 hydroxyphenols are toxic substances. If more than small amounts of the 

 free phenols accumulate, the animals will exhibit severe symptoms. It 

 has long been known that the animal possesses the capacity to conjugate 

 the phenols with products which render them non-toxic, and which may 

 readily be excreted via the kidney without causing any deleterious symp- 

 toms. It has repeatedly been demonstrated that almost all of the phenols 

 originating after the administration of benzene or after the feeding of free 

 phenol itself are excreted in conjugated form, and that practically no free 

 phenol is present. Although normal human urine contains practically no 

 free phenols (5 to 10 mg. conjugated phenols per liter), normal rabbit 

 urine is made up of 2 to 6 mg. of free phenols and 10 to 13 mg. of total 

 phenols per liter. ^^^ After feeding benzene, Porteous and Williams'** 

 recovered 9.2% as phenol and 11.5% as other phenols from the urine of 

 rabbits (total 20.7%) ; 9.5% of the products of benzene was excreted in 

 the form of ethereal sulfates, and 11.2% as glucuronides (total 20.7%). 

 It is evident that phenol itself and the other phenols are conjugated both 

 with sulfuric acid and with glucuronic acid. 



The proportion of the total phenol combined depends upon the nature 

 of the diet; it is highest on acid diets and lowest on basic regimens.'**'^"" 

 The amount excreted is decreased following repeated injections. '''''•2''° 

 Diuresis influences the ratio of the conjugated phenols. '™'^°'' 



"8 A. M. Tschernikow, I. D. Gadaskin, and 1. 1. Gurewitsch, Arch, exptl. Pathol. Phar- 

 niakol, 154, 222-227 (1930). 



198 A. E. Braunstein and A. N. Parschin, Biochem. Z., 2S5, 334-343 (1931). 

 200 A. E. Braunstein and A. N. Parschin, Biochem. Z., 235, 344-352 (1931). 



