Inhalation studies on the biotransformation and elimination of [formula omitted] and [formula omitted] in Beagles

Abstract

The possible biotransformation of trichlorofluoromethane (FC-11) and dichlorodifluoromethane (FC-12) was investigated in 4 male and 2 female adult Beagles after a short (6- to 20-min) inhalation. Dogs were anesthetized with ketamine and succinylcholine, intubated, and ventilated artificially. Trichlorofluoromethane (1000–5000 ppm, v v ) or dichlorodifluoromethane 38000–12,000 ppm, v v ) containing up to 180μ Ci of [ 14 C] fluorocarbon was delivered from 110-liter Teflon bags, and all exhalations were collected via a nonrebreathing valve in similar bags for 1 hr. Venous blood samples were withdrawn at appropriate times and assayed for fluorocarbon-associated radioactivity. Exhalation bags were assayed for [ 14 C] fluorocarbon and 14CO 2. Urine was collected for up to 3 days and assayed for 14 C metabolites as nonvolatile radioactivity. In some experiments animals were sacrificed 24 hr after exposure and tissues were removed for determination of nonvolatile radioactivity. Essentially all of the administered (inhaled) fluorocarbon was recovered in the exhaled air within 1 hr. Only traces of radioactivity were found in urine or exhaled carbon dioxide. All tissues contained measurable concentrations of nonvolatile radioactivity 24 hr after exposure but together represented less than 1% of the administered dose. It is not possible to determine if these trace levels are associated with metabolites of the fluorocarbons or with the unavoidable radiolabeled impurities present in the administered gas mixture. Neither phenobarbital pretreatment (60 mg/day for 3 days) nor prolonged exposure (50–90 min) produced any alteration of these results. Thus, it can be concluded that FC-11 and FC-12 are relatively refractory to biotransformation after a short inhalation exposure and that they are rapidly exhaled in their unaltered chemical form.