THE RELATION OF DOSAGE TO EFFECT. II

¹ From the United States Fisheries Biological Station, Beaufort, North Carolina, and the Physiological Laboratory, University of Utah

1. In the present study the test organisms have consisted of adults of the marine isopod, Limnoria, toad larvae from a few days to three weeks of age, and adult females of the brine shrimp, Artemia, from Great Salt Lake. Above 8000 handpicked individuals have been used.

2. The drugs which were studied consisted of ethyl alcohol, phenol, cocaine hydrochloride, hydrochloric and phosphoric acids.

3. In the majority of experiments dosage was changed by changing the time of exposure to the toxic solution, which was present in large excess. In certain experiments the concentration of the toxic solution was changed, the periods of exposure to the several concentrations remaining constant.

4. In all experiments effect was measured in terms of the percentage of deaths occurring within eighteen hours after return to a normal environment, following stated periods of immersion in a given drug solution.

5. The relation between dosage and effect is represented graphically by an S curve. It has been pointed out that the latter is a cumulative frequency curve of individual sensitivities of the organisms in a given population. It is proposed, therefore, to speak of this curve as the dose-effect (or toxicity) ogive.

6. The dose-effect ogive is independent of (a) the criterion of dosage, (b) the type of drug used, (c) the type of test organism, and (d) the rate at which the drug is absorbed.

7. The regularity with which a well-defined ogive has been obtained is ascribed, first, to the systematic use of test organisms which were relatively highly organized and in which, presumably, complicating changes in physiological state did not succeed each other as rapidly as in microorganisms; second, to the studied effort to obtain large populations of a maximal degree of homogeneity.

8. A consequence of the ogival relation between dosage and effect is that no mathematical function, the graph of which exhibits a steep slope in the region of minimal dosage can be used to describe this relationship. In other words, neither the ordinary monomolecular reaction formula, nor the simple logarithmic relationship embodied in the Weber-Fechner law, nor the formula for a parabola can be fitted to the present data.

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