Time scaling: Not applied. The cardiac sensitization response is a concentration-dependent threshold effect; dogs exposed to similar chemicals for longer durations responded in a similar manner. Therefore, the same concentration was used for all exposure durations.

Data adequacy: Humans exposed to halocarbons may develop cardiac arrhythmias. The cardiac sensitization test with the dog is a good model because the test is highly sensitive (i.e., the exogenous dose of epinephrine is at much greater than physiological levels). The concentration of 3,000 ppm is far below the highest 4–6 h nonlethal concentration of 45,781 ppm in studies with laboratory animals. Adjustment of the 45,781 ppm concentration by interspecies and intraspecies uncertainty factors of 3 each, for a total of 10, results in a higher concentration (4,600 ppm) than that derived from the cardiac sensitization data. Using repeated exposures, 8,000 ppm was a NOAEL and 20,000 ppm was a LOAEL for developmental effects associated with maternal toxicity in rats. Additional studies addressed neurotoxicity and carcinogenicity.



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