Rabbit Responses to Human Threshold Doses of A Bacterial Pyrogen

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Abstract
Summary: The scarcity and conflicting nature of the existing evidence on the relationship between effective doses of bacterial pyrogens in man and rabbit is pointed out. The dose/quantal response curve for man to a pyrogen prepared from P. vulgaris has been determined and the intravenous ED50 for this preparation is estimated to lie between 0·084 and 0·101 μg./kg. (P = 0·95). The dose/temperature response curves for the rabbit to the same pyrogen preparation, in a variety of different experimental circumstances, have been determined. The relative sensitivities of man and rabbit to this pyrogen have been calculated on a weight-for-weight basis. Taking as the criteria of pyrogenic response (a) a rise of 0·6° C. in the temperature of the rabbit and (b) shivering in man, it is found that the rabbit is one-third to 7 times as sensitive as man, depending on the experimental conditions. 5 The expected efficiencies of the B.P. and U.S.P. tests, in detecting a human ED5 of Pyrogen Test Preparation No. 1 in differing volumes of solution, have been calculated. 6 Some evidence that pyrogens may interact with other substances has been discussed.

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