FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



If the author merely expresses the maximum tolerated dose as a range (e.g. , "20 to 30 mg is 

 the maximum dose tolerated by the individual" or "20 to 30 mg is the maximum dose tolerated by 75% 

 of the individuals tested"), the CBCC codes the dose in Fields M, N, and P as an average of the limits 

 of this range and the Field Y rating is derived directly from the dosage field or through the Grid. 



When tests have demonstrated the maximum tolerated dose (or the largest dose not causing a 

 non-toxic response) and code evaluation is by Criterion 21, Field W is coded with Symbol or P. (See the 

 diagrams of Division 14. ) This follows the pattern of coding maximum tolerated dose determinations, 

 by which Field T is coded with the response which the dose coded in Fields M and N does not cause. 

 In other words, Field W is coded to indicate that the response coded in Field T has been produced and 

 the lowest dose that will cause the response to any degree has been determined (it does not indicate 

 that the dose coded in Field M or N is not that threshold dose, however); Symbol 21 in Field X provides 

 the coding clue to the fact that the dose in Field M or N is actually a concentration or quantity below 

 the threshold dose and that the evaluation in Field Y is not an evaluation of the compound's killing 

 ability but an expression of its degree of safety. 



16. Criterion 22; antagonism; the potency of the test compound for antagonizing COMPLETELY a 

 biological response to a secondary compound 



As its definition indicates, Criterion 22 is specifically for rating test compounds by a particular 

 chemical action, inhibition of another chemical's action on a biological system . 



It might be argued that the action of one compound on another is not a biological action under 

 any circumstances (even when the compound affected is a compound acting on a biological organism 

 and the action of this affected compound is the aspect affected by the test compound). Nevertheless, 

 a test compound's effect on the biological action of another compound is of such significance that it 

 is justifiable devising a way of recording and coding it. 



The special criteria that have been included in Field X for coding an effect of a test compound 

 on the biological action of another compound (hereinafter referred to as the "secondary compound" to 

 distinguish it from the test compound) are Criteria 22 and 55, which are used, under special conditions 

 described in this division, to rate antagonistic effects. Synergism, which is another effect a test 

 compound may have on the biological action of a secondary compound, is evaluated by Criteria 61 and 

 62, which, however, are not exclusively for evaluation of synergism. 



In connection with Criterion 22 (as well as with Criterion 55), it is worth noting here that 

 Field T-l has been equipped with the term "antagonizes" (Symbol 9 of Field T-l) as an action of the 

 test compound and since the test compound's net effect is the antagonism of the specific biological 

 response to the secondary compound, this biological response to the secondary compound is coded in 

 Field T-2. Unfortunately, it is not possible to code the secondary compound's specific action in 

 Field T-l, inasmuch as Field T-l has been used for indicating the test compound's inhibitory action; 

 therefore, it is always necessary to consult the written abstract on the Biology Code Sheet to learn 

 the secondary compound's action inhibited by the test compound. (See also Field T-l, Item 3 of 

 Division 12. ) 



Criterion 22 (as well as Criterion 55) can be regarded as placing a rating on the potency of the 

 test compound for performing the specific activity; in other words, it is rated according to the amount 

 of the test compound necessary to perform a definite level of activity in individual organisms. In the 

 case of both Criteria 22 and 55, the intensity of response in individual organisms is assumed to be the 

 complete antagonism (100%) of whatever response the secondary compound produced in the test 

 organism when administered alone. (I. e. , the criteria are not intended for incomplete antagonism, 

 such as "X units of test compound, when administered with Y units of secondary compound, antagonized 

 50% of the action of the secondary compound administered alone. ") This is explained in the second 

 paragraph below. With the intensity of response in individual organisms fixed by definition at 100%, 

 the test compound's potency is then dependent solely on the quantity needed to bring about this 

 complete antagonism of the secondary compound's biological action. This potency is not expressed 

 merely as the dosage coded in Field M, N, or P (as is the case with Criterion 20, or with Criterion 21), 

 but is expressed by comparing the quantity of the test compound needed to antagonize completely the 

 secondary compound's biological action to the quantity of the secondary compound that was antagonized. 

 The resulting value is then coded by reference to a special Field Y scale accompanying Criterion 22, 

 from which a Field Y code rating is derived. 



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