FIELD T- I 

 Column 57 



Evaluation of antagonism : For this, Criteria 22 and 55 may be used, if the 

 intensity of response has been reduced to zero (in case the test compound did 

 not produce the response when administered alone) or if the intensity of response 

 when the compounds are administered together is not greater than the intensity 

 of response when the test compound was administered alone (if the test compound 

 did produce the response when administered alone). Either of these intensities 

 of antagonism represents 100% antagonism of the secondary compound's action 

 for which Criteria 22 and 55 are defined. If the intensity of response to the two 

 compounds administered together is more than the intensities just described 

 (0 or more, but no greater than the intensity of response to the test compound 

 when administered alone), Criterion 62 must be used. 



II. Intensity of action of the test compound, when administered alone, is NOT KNOWN 



and the action of the test compound is NOT KNOWN to be the same as or to be opposite 

 to the action of the secondary compound. (See Figure 4. ) 



This situation is discussed above under heading A (A, II). If the intensity of 

 response, when the two compounds are administered together, is greater than 

 the intensity when the test compound is administered alone, the CBCC codes the 

 compound's effect as being additive, Symbol C. If the intensity of response is 

 less than the intensity when the secondary compound is administered alone, the 

 CBCC codes the test compound's effect as being antagonism of the secondary 

 compound, even if the action is opposite to that of the secondary compound when 

 administered alone. Evaluation of the additive effect or of the antagonism is 

 according to the explanation made above, following A, II and following B, I, (2). 



The four figures on the following page are included to assist the coder in understanding the 

 foregoing explanations of antagonism, synergism and additive effect. 



The second aspect of coding synergism, antagonism, and additive effect, listed at the beginning 

 of this division, is that of determining which, of two compounds administered together, shall be coded 

 as the acting agent (test compound, synergist, antagonist, or additive agent) and which shall be coded 

 as the affected compound (secondary compound, synergized or antagonized compound, or compound 

 whose effectiveness is merely supplemented, any of which would be coded in Field D) or, particularly 

 in the case of synergism and additive effects, whether each of the two compounds should be considered 

 in turn as the synergist or additive agent. 



In most cases of antagonism (Symbol 9), the choice is not the coder's responsibility and has 

 been stipulated by the author. Ordinarily, a compound candidate for antagonism of another compound 

 is one that, when administered alone, causes no response or causes the response at a considerably 

 lower intensity than do the compounds it is expected to antagonize. In any case, only one of the two 

 compounds is to be regarded as the antagonist and only one line is to be coded. 



When synergism (Symbol 8) has been demonstrated, it is frequently impossible to ascribe the 

 increased intensity of action of the two compounds administered together to one or the other of the two, 

 even if one of the compounds were inactive when administered alone; i. e. , it is frequently impossible 

 to discern which compound was synergized and which acted as a synergist. 



In the case of an additive effect (Symbol C), there is no real discrimination between the two 

 compounds as being either the compound whose action was added or the compound whose action was 

 added to . 



Nevertheless, the CBCC does not prepare a code line (on a second Code Sheet) for the second- 

 ary compound in which that compound would be coded as the test compound synergizing or adding to 

 the action of the compound coded on the first Sheet as the test compound. The CBCC restricts this 

 coding to a single line by selecting only one of the compounds to be coded as synergist (or as a 

 compound showing additive effect). With respect to this selection, if a whole series of chemicals 

 are tested for their synergistic or additive effect with one chemical, the chemicals in the series 

 should be regarded and coded as the test compounds and the single chemical against which they are 

 tested should be regarded and coded as the secondary compound. Therefore, if the CBCC files are 

 searched for (1) all activities of given compounds or for (2) all compounds showing synergism or 



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