RESPONSE AND ITS MEASUREMENT 447 



difference between the concentration which inhibits the most sensitive 

 spore and that required to prevent germination of the most resistant 

 spore. Conversely, a low slope, or flat dosage-response curve, indicates 

 that the difference in dose required for inhibition of the two extremes 

 of resistance is large (446). Slope is most conveniently measured as 

 the reciprocal of the difference between ED 84 and ED 50 . 



Although several factors of the assay influence slope, the compound 

 itself is the most significant (252). From this it has been argued that 

 the slope is an indication of the fundamental mode of action (174, 

 241, 279, 346, 416). That is, compounds with the same mode of action 

 should generate dosage-response curves of the same slope. Rich and 

 Horsfall (346) show that homologues of 2-imidazoline yield curves of 

 similar slope and different position; the ED 50 varied from 0.0037 to 

 3.57 ;u,M per square centimeter, but the slopes were essentially alike — 

 9.37, 11.01, and 9.97. From this and other experience, it is argued that 

 position measures ability of the compound to reach its site of action, 

 and that slope indicates the mode of action once the site has been 

 reached. 



Attractive as this hypothesis is, there are other factors that must give 

 us pause. First, as has been mentioned, non-linear curves are not un- 

 common. Second, there is as yet no measure of mode of action which 

 is truly independent and which could serve as a check on the hy- 

 pothesis. Finally, virtually all the available data are dosage-response 

 curves in which external concentration is the independent variable. 

 The discovery that fungi accumulate very large amounts of toxicant 

 (p. 450) does not by itself defeat the hypothesis, but this fact does 

 necessitate a re-evaluation of the whole problem (246). 



Spores of many fungi increase markedly in size during the first stages 

 of germination (Chapter 12); inhibition of this growth process in 

 Myrothecium verrucaria has been adapted to the bioassay of fungistatic 

 agents (268). 



Fungicidal Action. Fungicidal action, the killing of fungi by a 

 toxicant, requires an assay method in which cells are exposed to a 

 compound for a known period of time and are then removed from 

 contact with the toxic agent and tested for viability. Such assays have 

 been worked out for a variety of theoretical and practical problems (26, 

 69, 120, 128, 151, 246a, 250, 360, 463). 



The plot of probit of per cent germination against logarithm of time 

 is linear for the action of copper, silver, arsenate, and crystal violet 

 (250). The same plot of the data of Muller and Biedermann (302) 

 shows, however, that the strict exponential relation is evident only at 



