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HYDROFLUOROCARBON-23 37 riving an EEGL for use aboard submarines (vessels with no female crew members) this study has the most relevant exposure duration (total of 90 hr) of all the available studies, and no maternal or developmental toxicity was observed. Thus, the highest concentration tested of 50,000 ppm was considered to be the NOAEL. Because the available human data on HFC-23 are inadequate to determine the magnitude of difference between rats and humans, the subcommittee divided the NOAEL by an uncertainty factor of 10 to account for interspecies variability to yield a value of 5,000 ppm. The Navy's proposed 24- hr EEGL of 1,000 ppm is five times lower than that value and is therefore an adequate guidance level. To evaluate the Navy's proposed 90-day CEGL, the subcommittee used the 90-day toxicity studies in rats and dogs (Leuschner et al. 1983). For rats, the NOAEL was 10,000 ppm for 6 hr per day for 90 consecutive days, and for dogs, the NOAEL was 5,000 ppm for the same duration. The NOAELs in these studies were the only concentrations tested. The subcommittee believes that they are probably lower than the true NOAEL for HFC-23 because NOAELs reported in 90-day studies of similar HFCs were higher; for example, the NOAEL was 40,000 ppm for HFC-143a (Brock et al. 1996) and 50,000 ppm for HFC-125 (Nakayama et al. 1993 as cited in Kawano et al. 1995) and HFC-134a (Hext 1989; Collins et al. 1995). Furthermore, HFC-23 had no maternal or fetal effects in a developmental toxicity study at a concentration of 50,000 ppm. Given this, an uncertainty factor to adjust for the 6 hr per day exposures was not used. However, an uncertainty factor of 10 was applied to the NOAELs to account for interspecies variability, giving values of 1,000 ppm and 500 ppm, respectively. Because the Navy's proposed 90-day CEGL of 100 ppm is 5-fold lower than 500 ppm, the subcommittee finds the Navy's exposure guidance levels to be adequately protective of health for prolonged exposures. REFERENCES Andrews, P.W. 1996a. Salmonella Typhimuriam Microsome Reverse Mutation Assay. Proj. No. ILS A073-001. Integrated Laboratory Systems, Durham, N.C. Andrews, P.W. 1996b. AS52/GPT Mammalian Mutagenesis Assay. Proj. No. ILS A073-003. Integrated Laboratory Systems, Durham, N.C. Azar, A., H.J. Trochimowicz, J.B. Terrill, and L.S. Mullin. 1973. Blood levels of fluorocarbon related to cardiac sensitization. Am. Ind. Hyg. Assoc. J. 34:102-109. Branch, C.A., D.A. Goldberg, J.R. Ewing, S.C. Fagan, S.S. Butt, and J. Gayner. 1994. Evaluation of the acute cardiac and central nervous system effects of the fluoro
HYDROFLUOROCARBON-23 38 carbon trifluoromethane in baboons. J. Toxicol. Environ. Health 43:25-35. Branch, C.A., J.R. Ewing, S.C. Fagan, D.A. Goldberg, and K.M.A. Welch. 1990. Acute toxicity of a nuclear magnetic resonance cerebral blood flow indicator in cats. Stroke 21:1172-1177. Brock, W.J., H.J. Trochimowicz, C.H. Farr, R.J. Millischer, and G.M. Rusch. 1996. Acute, subchronic, and developmental toxicity and genotoxicity of 1,1,1-trifluoroethane (HFC-143a). Fundam. Appl. Toxicol. 31:200-209. Clayton, J.W., Jr., D.B. Hood, and J.W. Williams. 1960. Acute Testing. Rep. No. 25-60. Haskell Laboratory, Newark, DE. Collins, M.A., G.M. Rusch, F. Sato, P.M. Hext, and R.J. Millischer. 1995. 1,1,1,2- Tetrafluoroethane: repeat exposure inhalation toxicity in the rat, developmental toxicity in the rabbit, and genotoxicity in vitro and in vivo. Fundam Appl. Toxicol. 25:271-280. Detre, J.A., C.J. Eskey, and A.P Koretsky. 1990. Measurement of cerebral blood flow in rat brain by 19F-NMR detection of trifluoromethane washout. Magn. Reson. Med. 15:45-57. Ewing, J.R., C.A. Branch, S.C. Fagan, J.A. Helpern, R.T. Simkins, S.M. Butt, and K.M.A. Welch. 1990. Fluorocarbon-23 measure of cat cerebral blood flow by nuclear magnetic resonance. Stroke 21:100-106. Fagan, S.C., A.A. Rahill, G. Balakrishnan, J.R. Ewing, C.A. Branch, and G.G. Brown. 1995. Neurobehavioral and physiologic effects of trifluoromethane in humans. J. Toxicol. Environ. Health 45:221-229. Fleming, A.J. 1945. Kitchen Tests on âFreonâ Refrigerants. Rep. No. 0023-45. Haskell Laboratory, Newark, DE. Foltz, V.C., and R. Fuerst. 1974. Mutation studies with Drosophila melanogaster exposed to four fluorinated hydrocarbon gases. Environ. Res. 7:275-285. Hardy, C.J., and P.C Kieran. 1993. Halon 13B1, Freon 23, Mixture of Freon 23 and HFC 125, Assessment of Cardiac Sensitisation Potential in Dogs. DPT 273/921009. Huntingdon Research Centre Ltd., Huntingdon, Cambridgeshire, England. Hext, P.M. 1989. HFC-134a: 90-Day Inhalation Toxicity Study in the Rat. ICI Rep. No. CTL/ P/2466. Central Toxicology Laboratory, Imperial Chemical Industries, Alderley Park, Macclesfield, Cheshire, U.K. Hopkins, R.M., and J.C. Krantz. 1968. Relative effects of haloforms and epinephrine on cardiac automaticity. Anesth. Analg. 47:56-67. Kennedy, G.L., and S.D. Nash. 1980. Inhalation Approximate Lethal Concentration. Rep. No. 641-80. Haskell Laboratory, Newark, DE. Lee, W.R., S. Abrahamson, R. Valencia, E.S. von Halle, F.E. Wurgler, and S. Zimmering. 1983. The Sex-linked recessive lethal test for mutagenesis in Drosophila melanogaster, a report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutation Res. 123:183-279. Leuschner, F., B.W. Neumann, and F. Hubscher. 1983. Report on subacute toxicological studies with several fluorocarbons in rats and dogs by inhalation. Arzneim.-Forsch. 33:1475-1476.
HYDROFLUOROCARBON-23 39 Longstaff, E., M. Robinson, C. Bradbrock, J.A. Styles, and I.F.H. Purchase. 1984. Genotoxicity and carcinogenicity of fluorocarbons: assessment by short-term in vitro tests and chronic exposure in rats. Toxicol. Appl. Pharmacol. 72:15-31. Mullin, L.S., C.F. Reinhardt, and R.E. Hemingway. 1979. Cardiac arrhythmias and blood levels associated with inhalation of Halon 1301. Am. Ind. Hyg. Assoc. J. 40:653-658. Munley, S.M. 1997. HFC-23: Inhalation Developmental Toxicity Study in Rats. Rep. No. 995-96. Haskell Laboratory, Newark, DE. Naval Surface Warfare Center. 1997. Subject: Refrigerant decomposition in submarine CO-H2 burners. Letter to Commander, Naval Sea Systems Command, from Commander, Carderock Division, Naval Surface Warfare Center, Philadelphia, PA., dated June 24, 1997. Reinhardt, C.F., A. Azar, M.E. Maxfield, P.E. Smith, Jr., and L.S. Mullin. 1971. Cardiac arrhythmias and aerosol âsniffing.â Arch. Environ. Health 22:265-279. Tice, R.R. 1996a. Repeated Inhalation Exposure of FE-13 in Mice, Mus musculus (Bone Marrow Micronucleus Assay). Proj. No. ILS A073-002. Integrated Laboratory Systems, Durham, N.C. Tice, R.R. 1996b. In Vitro Chromosome Aberrations Study in Chinese Hamster Ovary (CHO) Cells. Proj. No. ILS A073-004. Integrated Laboratory Systems, Durham, N.C. Trochimowicz, H.J., A. Azar, J.B. Terrill, and L.S. Mullin. 1974. Blood levels of fluorocarbon related to cardiac sensitization: Part II. Am. Ind. Hyg. Assoc. J. 35:632-639.
