Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and HCFC-123 (1996)

The U.S. Air Force requested that the NRC evaluate the adequacy of the 1-min EEGL for hydrochlorofluorocarbon (HCFC)-123 that was proposed by toxicologists at Wright-Patterson Air Force Base. HCFC-123 is a proposed substitute for Halon 1211, the fire extinguisher currently used by the Air Force. Appendix A of this report contains the documentation prepared by Air Force toxicologists in support of the proposed 1-min EEGL for HCFC-123. This supporting documentation was submitted to the subcommittee for consideration. It contains the background information on HCFC-123, reviews the toxicokinetics, toxicity, and exposure information and provides recommendations for exposure guidance levels.

The documentation presented in Appendix A has been reviewed and revised in response to the subcommittee's comments. For HCFC-123, the end points of pharmacological or adverse effects considered for establishing an EEGL are cardiac sensitization, anesthesia or CNS-related effects, malignant hyperthermia, and hepatotoxicity.

Cardiac sensitization was chosen as the most sensitive end point because of the sensitizing effect of this chemical and similar chemicals in the epinephrine-challenged dog model. The EC₅₀ for HCFC-123 was determined to be 1.9% (19,000 ppm) for a 5-min exposure (Trochimowicz and Mullin, 1973). The Air Force toxicologists recommended that the EC₅₀ of 19,000 ppm be the 1-min EEGL for the HCFC-123. However, the subcommittee believes that 1,900 ppm (19,000 ppm divided by an uncertainty factor of 10 for interspecies variability) should be considered the human NOEL for a 1-min exposure to HCFC-123 in humans on the basis of the dog cardiac-sensitization model. Therefore, the subcommittee recommends that the 1-min EEGL of 19,000 ppm proposed by the Air Force be lowered to 1,900 ppm.

The justification for using the LC₅₀ for developing the 1-min EEGL is as follows: (1) actual duration of exposure for humans would be one-fifth the duration of the dog-test exposure; and (2) tissue concentrations in humans would be much less in a 1-min exposure than those in the 5-min exposure of dogs.

Trochimowicz, H.J., and L.S. Mullin. 1973. Cardiac Sensitization Potential (EC₅₀) of Trifluorodichloroethane. Haskell Laboratory Rep. 132-73. Haskell Laboratory for Toxicology and Industrial Medicine , Wilmington, Del.