The assay of endotoxin by intravenous injection of lead acetate-treated mice

Abstract

A new intravenous endotoxin assay method (i.v. method) for the determination of very small amounts of endotoxin was studied in mice pre-treated intraperitoneally with lead acetate and was compared with an earlier intraperitoneal (i.p.) method in which both endotoxin and lead acetate were administered by the i.p. route. Linear dose-response relationships were obtained for both the i.v. and i.p. methods between logarithmic doses of endotoxin and the responses measured as body weight ratios on the first day. The range of the linearity was longer in the i.v. method than that in the i.p. method. In the i.v. method, linearity extended to much smaller doses of endotoxin than in the i.p. method. The slope of the dose-response line obtained by the i.v. method was flatter than that obtained by the i.p. method. The minimum detectable dose defined as the smallest dose of endotoxin producing a mean response statistically distinguishable from that of the control was in the nanogram order and smaller than that obtained by the i.p. method. Therefore the i.v. method may be more suitable than the i.p. method for detection of very small amounts of endotoxin. The non-parallelism of the dose-response lines obtained in lead acetate-treated and untreated mice was demonstrated in the i.v. method as well as in the i.p. method.