Muconic acid as a metabolic product of benzene.

JAFF, [1909] isolated muconic acid from the urine of rabbits and dogs to which benzene had been administered. The amount was approximately 03% of the benzene given, but Jaff6 considered that a larger amount was formed in the tissues, possibly as much as 25-30%, by the opening of the benzene ring, because he found that injected muconic acid was metabolized, only about 1% being recovered in the urine. Fuchs & Soos [1916] found muconic acid in the urine of patients who had been treated for leucaemia with benzene. The yield was also small (0O1%1 %). Higher yields, corresponding to about 3 7% of the benzene administered, have been recorded by Thierfelder & Klenk [1924], but not every investigation has confirmed Jaff6's work. Neumaerker [1923] failed, in spite of using an improved method of extraction, to separate any muconic acid from the urine of a rabbit which had been injected subcutaneously with 3 g. of benzene. The question which needed further study was that of the origin of the muconic acid, because, apart from some uncertainty whether it is always produced, there was the important consideration, based on the work of Boeseken and his colleagues [1929; 1932], that one would expect the cis-cis form of the acid to be formed, whereas the evidence indicated that the acid isolated from urine was the trans-trans form. B6eseken & Slooff [1929] have remarked, "If it should really be true that on addition of benzene to the food, trans-trans acid was separated by the test animals, this is more likely the consequence of a reduction and dehydration, e.g. of galactose, as the grouping of the atoms of this sugar and the closely allied mucic acid renders the formation of trans-trans muconic acid possible." The suspicion that the muconic acid in the urine might arise not directly from the benzene but as a result of disturbances of metabolism caused by it seemed to be strengthened by the discrepancies regarding the fate of the acid after it is injected into animals. Jaff6 [1909] recovered less than 1 %; Neumaerker [1923] as much as 53 %; Mori [1918] the very high yield of 73%. The last-mentioned investigator was inclined to doubt that the acid was formed after giving benzene. EXPERIMENTAL