FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



The explanation for the assumption of 100% antagonism for Criterion 22 (and Criterion 55) lies 

 with the procedure for deriving the Field Y evaluation. If it is assumed that the antagonism of the 

 secondary compound's action can be accomplished by test compounds at varying degrees less than 

 100%, the quantity of test compound needed for a lower degree of antagonism (40% or 75% antagonism, 

 e.g. ) should presumably be less than the quantity needed for complete antagonism. If the degree of 

 antagonism is ignored and the quantity administered causes less than complete antagonism, the dosage 

 ratio and Field Y code evaluation will be too low. The CBCC has established no criterion for the specific 

 case of antagonism known to be less than 100%. If the test compound proves incapable of antagonizing 

 completely the secondary compound's action, regardless of the quantity of test compound administered, 

 or if the highest dose of test compound administered causes less than complete antagonism (without 

 demonstrating that this is the maximum intensity of antagonism of which the test compound is capable), 

 only Criterion 62 (percent response) is available for recording the degree of antagonism regardless of 

 the quantity of test compound needed to produce that degree. This is discussed further in the second 

 paragraph of Division 21. 



It may not be immediately clear the reason for establishing evaluation on the basis of a corre- 

 lation of the dose of test compound with the dose of secondary compound; consideration of all the factors 

 involved tends to be confusing. It should be observed that (1) the specific response of the test organ- 

 ism to the secondary compound may characteristically vary in intensity , according to the size of dose 

 of secondary compound administered and (2) the dose of secondary compound administered in the test 

 need not always be assumed to be the minimum dose needed to cause the maximum intensity of response. 

 In many cases of antagonism, the size of the dose of test compound needed to antagonize the secondary 

 compound's biological effect depends upon what total quantity of secondary compound the test compound 

 must act upon, since the antagonism is regarded as purely an interaction between the two compounds. 

 Thus, (1) if the intensity of biological response to the secondary compound can vary or (2) if the dose of 

 secondary compound were higher than needed to produce the organism's response intensity (this response 

 intensity's reduction being the only clue to antagonistic activity of the test compound), it will be seen 

 that the dose of secondary compound might be a variable and consequently the dose of test compound 

 needed to antagonize it would be a variable . In other words, considering possibilities (1) and (2) above, 

 it is possible that the test could be repeated, employing in the second test a dose of secondary compound 

 larger or smaller than the dose administered in the first test, to induce adequately the same biological 

 response. The response in the second test would subsequently be shown to be antagonized by a dose of 

 test compound higher or lower , respectively, than in the first test. Thus, if evaluation were based on 

 dose size of test compound alone, without knowing whether the secondary compound dose was the mini- 

 mum needed for a given response intensity, the expression would be meaningless as an evaluation of 

 the test compound's ability to antagonize the specific response (Field T) of the test organism (Field E) 

 to the specific secondary compound. The only alternative has been to regard antagonism as a quantita- 

 tive chemical interaction and assume that, when antagonism has been complete (see the preceding para- 

 graph), a calculation indicating what dosage of secondary compound is antagonized by each unit of test 

 compound will represent a reasonable evaluation of the test compound's ability to antagonize the sec- 

 ondary compound relative to the specific response and test organism involved and relative to other test 

 compounds. 



In using the dosage ratio for deriving a code evaluation, an assumption is made which should be 

 recognized, namely that the ratio is assumed to be the same, regardless of the size of the dose of the 

 secondary compound. For example, it assumes that when the biological response to a secondary com- 

 pound, administered at a dose of 5 grams, is completely antagonized by 0. 5 grams of test compound, the 

 greater biological response to 50 grams of that secondary compound will be completely antagonized by 

 5 grams of test compound. This should probably not be assumed and therefore, the code rating derived 

 by Criterion 22 should always be interpreted in terms of the actual size indicated by the coding in Fields 

 M and N rather than mere relative size of the doses of the test compound and secondary compound, as 

 indicated by the ratio (written on the Code Sheet and by the code symbol in Field Y). 



When the antagonism of the response to the secondary compound has been demonstrated to be 

 the maximum antagonism of which the test compound is capable and the test compound dose is the 

 minimum dose producing this degree of antagonism, Field W is always coded with Symbol regardless of 

 whether the maximum antagonism is 100% (Criterion 55) or less than 100% (Criterion 62). As indi- 

 cated earlier, if the test compound dose is not known to be the minimum dose, Field W should be coded 

 with Symbol M or N. If the antagonism is less than 100% (Criterion 62) and the test compound has 

 not been proved incompetent for causing greater antagonism with larger doses, use Symbol P in Field W. 

 If only one dose is given and less than 100% antagonism results (Criterion 62), code Field W with 



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