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J. H. ANNEGERS, M.S.; F. E. SNAPP, M.S.; A. C. IVY, Ph.D., M.D.; A. J. ATKINSON, M.D.
Arch Intern Med (Chic). 1944;73(1):1-6. doi:10.1001/archinte.1944.00210130009001.
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Those investigators who have observed damage to the liver after administration of cinchophen to laboratory animals used doses at least ten times the equivalent dose for human beings estimated on the basis of body weight.1 Those who have used the same or smaller doses failed to find any striking evidence of hepatic damage 2 or of depression of hepatic function.3 Stalker, Bollman and Mann 4 gave twice the average human dose to a relatively large number of dogs for periods up to thirty-nine weeks. Though they observed gastrointestinal intolerance, which usually subsided, they did not observe jaundice or microscopic evidence of pathologic changes in the liver and other tissues, other than "peptic ulcer."

It was believed that if cinchophen has a direct toxic effect on the liver it should be manifested by a disturbance of secretion of cholic acid, since the output of that substance is readily affected by an


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