Issued April 4, 1912. U.S. DEPARTMENT OF AGRICULTURE, BUREAU OF CHEMISTRY--BULLETIN No. 148. H. W. WILEY, CHIEF OF BUREAU. THE TOXICITY OF CAFFEIN: AN EXPERIMENTAL STUDY ON DIFFERENT SPECIES OF ANIMALS. BY WILLIAM SALANT, _Chief Pharmacological Laboratory, Division of Drugs_, AND J. B. RIEGER, _Assistant Chemist_. [Illustration: UNITED STATES DEPARTMENT OF AGRICULTURE SEAL] WASHINGTON: GOVERNMENT PRINTING OFFICE. 1912. LETTER OF TRANSMITTAL. U. S. DEPARTMENT OF AGRICULTURE, BUREAU OF CHEMISTRY, _Washington, D. C., November 14, 1911_. Sir: I have the honor to submit for your approval a manuscript on the toxicity of caffein, which is the first of a series of reports to be made by Dr. Salant on the pharmacology of this drug; the conclusions here reported are, therefore, in some particulars to be regarded as tentative. The data obtained are primarily of use in the execution of the food and drugs act, but are capable of much broader application. Acknowledgment is made of the assistance rendered by Dr. John R. Mohler, Chief of the Pathological Division, Bureau of Animal Industry, and his assistants, in performing the autopsies recorded in this report. I recommend the publication of the manuscript as Bulletin No. 148 of the Bureau of Chemistry. Respectfully, H. W. WILEY, _Chief_. Hon. JAMES WILSON, _Secretary of Agriculture_. This publication may be procured from the Superintendent of Documents, Government Printing Office Washington, D. C., at 15 cents per copy CONTENTS. Page. Introduction 5 Historical review of the literature on the toxicity of caffein 9 Acute caffein intoxication 18 Experiments on rabbits 18 Subcutaneous injection 18 Administration by mouth 26 Injection into the peritoneal cavity 28 Intramuscular injection 33 Intravenous injection 37 Summary 42 Experiments on guinea pigs 43 Subcutaneous injection 43 Injection into the peritoneal cavity 47 Administration by mouth 49 Summary 52