FIELDS W, X. and Y 



Columns 68; 69 and 



70; and 71 



In determining the threshold dose for a specific action, a single individual organism can con- 

 ceivably be used, administering successively larger doses, separated by appropriate intervals, till 

 the threshold point is reached. (These sub-threshold doses need not be written on the Code Sheet and 

 they must not be coded; only the threshold dose should be coded in Fields M, N, and P. ) The more 

 common test procedure, however, involves administering each of the different sized test doses to 

 different individuals, in which case the smallest dose producing the response to any degree in that 

 group of individuals is interpreted as the threshold dose. (This does not concern determination of the 

 percentage of individuals responding to that lowest dose. The determination of percentage of individuals 

 whose threshold response is with a given dose is a more infrequent and critical test discussed later in 

 the division. ) 



Since Criterion 20 places a rating on the compound according to only the size of the dose , as 

 explained in the first paragraph of this division, the rating coded in Field Y is determined by reference 

 to the coding of the threshold dose in Field M, N, or P. (Note the following paragraph. ) The size of 

 the dose in the dosage field is indicated by the coding in Column 48 of Field N (or in Column 46 of 

 Field M or Column 51 of Field P). This is merely transferred to Field Y as the rating for comparison 

 with other compounds. A low figure used as a symbol in Field M, N, or P indicates a low dosage; a 

 low figure used as a symbol in Field Y indicates a low response; since a low threshold dose indicates 

 a high potency, it is necessary to use in Field Y the reciprocal of the figure used in Field M, N, or P, 

 as follows: 



Field M, N, or P: Field Y: 



coding in Col. 46, Coding in 



48, or 51 Col. 71 



1 9 



2 8 



3 7 



4 6 



5 5 



6 4 



7 3 



8 2 



9 1 



The threshold dose will usually be in Field N, because it is most frequently determined and 

 expressed as the actual quantity of pure compound, or equivalent, administered in a single dose. For 

 purposes of comparison of compounds' threshold doses, this quantity given as a single dose to produce 

 threshold response (Field N) is the preferable one, though in certain types of therapy which are neces- 

 sarily or typically by a series of administrations, the threshold dose size might be defined best in 

 terms of Field P or Field M. If the threshold dose evaluation is based on "duration of administration" 

 (Field P) or "concentration" (Field M), the coder should always clearly indicate it in the written 

 abstract for Field Y. 



The threshold dose is probably never more than an approximation even under the most exacting 

 conditions, due to differences between test organism individuals and variables in conditions prevailing 

 at different determinations of the dose. Therefore, for therapeutic drugs, an effort might be made to 

 determine the variation in thresholds of a given response in several individuals. (For example, "in 10% 

 of the organisms, the threshold dose was 1 mg; in 20%, it was 1. 5 mg; in 50%, it was 5 mg; and in 20%, 

 it was 10 mg". ) In this event, the CBCC plots the data on the Grid (double coding the dosage field 

 with the extremities of the range of threshold doses corresponding to the range represented by the eval- 

 uation symbol coded in Field Y), as explained in Division 8 (Subdivision B) and Division 24. This is in 

 lieu of selecting only one of the threshold determinations (of the range of thresholds demonstrated in 

 the group of individuals) and giving it a Field Y rating according to that selected threshold dose , or of 

 constructing a separate code line for each. The procedure is possible by regarding one of the three 

 factors involved (individual intensity of response vs. dose size vs. percent of organisms)--the intensity 

 of response of the single individual of the species tested- -to be non- variable at threshold level; the 

 remaining two factors can be plotted as variables to derive an evaluation correlate. Note that when 

 plotting a dose size against a percent of organisms responding, CRITERION 20 CAN NOT BE USED, but 

 only Criterion 51, 52, or 53. 



193 



