RT Journal Article SR Electronic T1 A COMPARISON OF THE ACUTE AND CHRONIC TOXICITY OF CARBON DIOXIDE WITH ESPECIAL REFERENCE TO ITS NARCOTIC ACTION JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 11 OP 21 VO 78 IS 1 A1 J. H. BARBOUR A1 M. H. SEEVERS YR 1943 UL http://jpet.aspetjournals.org/content/78/1/11.abstract AB The acute and chronic toxicities of carbon dioxide have been compared and certain factors concerned in its narcotic action have been investigated. 1. The maximal tolerated concentration of CO2 for the albino rat after sudden exposure is approximately 15%. However, when the final concentration of CO2 is attained gradually over several days, the maximal tolerated concentration is approximately 23%. Likewise, a greater degree of depression is produced by sudden exposure to a given concentration of CO2 than by prolonged exposure to the same concentration, indicating that the rat is capable of a certain degree of acclimatization. 2 Following sudden exposure to 11% CO2, there is a temporary decrease in the total oxygen consumption of the rat. This reaches a level 15 to 25% below normal within two to four hours and slowly returns to the normal range within twenty-four hours of continued exposure. When the rat is placed in atmospheres with gradually increasing concentrations of CO2, the oxygen consumption remains within normal limits until concentrations of CO2 greater than 10% are attained. 3. During exposure to 11% CO2 for thirty days, the plasma pH falls to a level as low as 7.09 in the first half hour and remains below 7.15 during the remainder of the period. The CO2 content of the blood gradually increases to 130 to 148 volumes %. 4. A marked reticulocytosis occurs in the rat during prolonged exposure to 11% CO2, but no corresponding increase in the number of leukocytes or erythrocytes is observed. 5. The sleeping time of normal rats anesthetized with pentobarbital is prolonged in atmospheres containing 10 or 20% CO2. Similar results are obtained with rats previously exposed to 10% CO2 for one week. Evidence is presented which suggests that CO2 delays the detoxication of pentobarbital by diminishing the blood flow through the liver as a result of the splanchnic vasoconstriction.