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Iodotrifluoromethane: Toxicity Review
concentration that does not produce an arrhythmia in the dog, will also not cause one in a human. As has been shown in studies with HCFC-142b and CFC-113 (NRC 1996), administration of epinephrine results in a highly sensitive model; this supports the assumption.
Although they were not included in the statement of work for the subcommittee, the Army posed several questions with regard to the cardiac-sensitization potential of CF3I, and the subcommittee strove to address them. What follows is the first question and the subcommittee’s response. The other questions are discussed at the end of Chapter 5.
Is the information from cardiac-sensitization tests in dogs appropriate for developing safe exposure levels in humans? If these studies are valid to serve as a basis for human exposure levels, should the data be extrapolated to humans directly without using uncertainty factors? The subcommittee found that although it is difficult to ascertain absolutely that cardiac-sensitization studies in the dog are appropriate for developing safe exposures for humans, a substantial body of evidence nevertheless indicates that many halocarbons that produce cardiac arrhythmias in the dog also cause them in humans. No uncertainty factors are necessary for extrapolation from dogs to humans, because the doses of exogenous epinephrine achieve plasma concentrations that are 10 times greater than those achieved during physiologic stress. Therefore, the dog cardiac-sensitization test procedures are conservative enough to account for any uncertainty in dog-to-human extrapolations.