Metabolism of 1,1-dichloro-2,2,2-trifluoroethane in rats

Abstract

1. Chlorofluorohydrocarbons are presently being developed as alternatives for ozone-depleting chlorofluorocarbons. 1,1-Dichloro-2,2,2-trifluoro-[2-¹⁴C]-ethane (HCFC-123) is a chlorofluorohydrocarbon with potential widespread use and associated human exposure. As a part of the toxicological evaluation of HCFC-123, its metabolism was studied in rodents in a closed recirculating exposure system.

2. Two male rats were individually exposed for 6 h. Excretion of radioactivity was monitored for 48 h after the start of the exposure. Of the radioactivity introduced into the chamber, 14% was recovered in urine within the period of observation. Excretion of metabolites in the urine was very slow.

3. Trifluoroacetic acid was the major metabolite of HCFC-123 and N-trifluoroacetyl-2-aminoethanol and N-acetyl-S-(2,2-dichloro-1,1-difluoroethyl)-L-cysteine were identified as minor urinary metabolites of HCFC-123.

4. Forty-eight hours after the start of the exposure, covalent binding of radioactive metabolites to protein was highest in liver followed by kidney and lung. Covalent binding above background levels was not observed in pancreas and testis, the target organs of HCFC-123 tumourigenicity.

5. These results suggest that the biotransformation of HCFC-123 in rodents follows a pathway identical to those of the extensively studied structural analogue halothane.