A Method for Titrating Endotoxic Activity in the Skin of Rabbits

The primary inflammatory response of rabbits to intradermal injection of bacterial products has been used as the basis of a sensitive assay for endotoxins. Injection of materials into the skin of the lateral surfaces, rather than the ventral surface of the abdomen, was essential. The method was evaluated by comparison with the mouse toxicity test. Statistical examination revealed an excellent correlation between the mean threshold dose for producing skin lesions in rabbits (SLD(50)) and the median lethal dose for mice (LD(50)). For potent endotoxins (LD(50) = 0.2-0.3 mg.) the skin test dose was about one-thousandth of the lethal dose for mice. Thereafter the LD(50) increased in the proportion of about 0.3 mg. per 1 microg. increase in SLD(50). The method of testing was devised for endotoxins prepared in various ways from Salmonella enteritidis and S. typhosa but was directly applicable to endotoxins from several other species of enteric Gram-negative bacteria.