FIELDS W, X, and Y 

 Columns 68; 69 and 

 70; and 71 



Lacking a means of correlating the two factors, dose size and degree of synergism, the most 

 reasonable basis for evaluation has seemed to be the maximum degree of synergism of which the test 

 compound is capable. (Although it is probably not always true that the testing procedure guarantees to 

 have demonstrated this maximum capability of the test compound, it is apt to be most often the 

 maximum. ) Thus, the Field Y evaluation of synergism is not based on dose size nor is it a correlate of 

 dose size and degree of synergism (in contrast to the evaluation of antagonism which i_s based on dose 

 size). 



The CBCC has rather arbitrarily designated two synergism intensity categories, one consisting 

 of test compounds which can synergize the secondary compound action only to 100% or less than 100% 

 and a second consisting of compounds that synergize actions to a greater degree than 100%. These 

 are coded by two separate criteria in the Code, Criterion 62 for 100% and less than 100% response 

 and Criterion 61 for more than 100% response. The second factor, dosage size of the test compound, 

 is also important, and in interpreting the comparative ability of a test compound for synergizing a 

 specific secondary compound's action, reference must be made to the relative quantities of test 

 compound (synergist) and secondary compound (compound whose action is synergized), as compared to 

 the ability of other test compounds for synergizing the same secondary compound's action. In other 

 words, the interpreter of the code line must relate the evaluation of Field Y to the dose coded in Field 

 M or N (test compound) and to the quantity of secondary compound which should be written in Field D 

 by the coder. 



It should be mentioned that prior to this edition of the Code, synergism was given a code 

 evaluation according to special criteria (designated as Criteria 56 and 60). Criterion 56 involved a 

 dosage ratio similar to that of Criterion 55 (the quantity of synergist divided by the quantity of compound 

 synergized) which provided a relative dosage value which in turn was correlated on the Grid with the 

 intensity of synergism (percentage increase in the response to the secondary compound). Criterion 60 

 was used for evaluation of synergistic response intensities of more than 100% and based evaluation 

 merely on the intensity, attempting no correlation with dose size. In the present edition, Criterion 60 

 has been omitted, since it provided nothing more than does Criterion 61 (if Field T-l is coded properly 

 with Symbol 8). Criterion 56 has been omitted because its use of the Grid for correlating relative 

 dose size and degree of synergism has not seemed to be an accurate procedure and because it would 

 seem that if synergism of greater intensity than 100% is to be evaluated according to its intensity 

 only, it may as well be coded consistently by that procedure, even when less than 100%. 



If the synergistic activity has been demonstrated to be the maximum intensity of which the test 

 compound is capable, Field W should properly be coded with Symbol N or 0, according to whether the 

 dose coded in Field M or N is known to be the minimum needed. If the dose is known to be either less 

 than the minimum needed to cause maximum intensity of response or the minimum needed to cause 

 maximum response, but it is not known which, code Field W with Symbol P. If the test compound is 

 administered at only one dose level which is therefore not known to be the dose causing maximum 

 synergism of which the compound is capable, nor the minimum dose needed to cause the synergism 

 produced, Field W would be coded with Symbol L or M, according to whether the dose administered is 

 known to be the maximum tolerated. If the test compound proved incapable of causing synergism, 

 Criterion 62 must be used (or Criterion 01) with Symbol 1 in Field Y and with Field W coded with 

 Symbol J or K, according to whether the dose was administered at the maximum tolerated level. This 

 is discussed in the last part of the section on General Use. 



23. Criteria 61 and 62; evaluation based solely on intensity of response regardless of the 

 quantity of te,st compound 



These criteria are used for specific responses (including synergism and antagonism) which may 

 occur at various degrees of intensity in the individual organism. (See Subdivision A of Division 8. ) 

 Criteria 61 and 62 make no correlation between the intensity of response (percentage response in the 

 individual organism) and the minimum quantity needed for that response (coded in the dosage fields) to 

 derive a Field Y evaluation expression. Therefore, the evaluation afforded by Criterion 61 or 62 is not 

 an expression of the test compound's potency as it is defined in Division 8. Criteria 61 and 62 repre- 

 sent two categories of response intensity, 62 being for no response and for responses of 100% or less 

 and 61 being for responses of more than 100%. 



Criterion 61 or 62 must be used whenever the biological response is of the type that occurs at 

 various intensities beyond the threshold response intensity in the individual organism and the author 



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