Relationship of lethal toxic dose to body weight of the mouse

Abstract

LD50's have been determined for tetrodotoxin, hemicholinium-3, d-tubocurarine, strychnine, α-naphthylthiourea, 48–80 (a histamine liberator), picrotoxin, sodium fluoroacetate, McN-A-343 (a ganglionic stimulant), hexamethonium chloride, pentamethylene tetrazol, sodium pentobarbital, atropine, histamine, and sodium barbital by intraperitoneal injection into small, medium, and large male and female mice. Values have also been determined for histamine and α-naphthylthiourea by intravenous injection. An attempt has been made to describe the relationship of toxicity to body weight for each of these instances. While the most common relationship found is a direct linear one characterized by a slope of unity when the logarithm of dose is plotted against the logarithm of body weight, a significant number of cases show a variety of other relationships to preclude any overall generalization. Only hemicholinium-3 in the female mouse came close to duplicating the published experience with botulinal and tetanal toxins. Experimental evidence is provided to demonstrate that the character of the relationship may vary with drug identity, route of administration, and sex of the test organism. There is no reason to expect that species, strain, and the other factors known to modify the intensity of drug action will not also modify the relationship of effective dose to body weight. The influence of each of these factors is, however, not predictable on the basis of present knowledge.