FIELD X 



Columns 69 and 70 



FIELD Y 

 Column 71 



Field X 



Field Y 



21 Maximum tolerated dose (abbreviation: 

 MTD). 



Most frequently this is understood to be 

 the greatest quantity that can be adminis- 

 tered without causing death (Field T-2, 

 Symbol U, 111, or 1 12) of the test organ- 

 ism; i. e. , the dose just smaller than the 

 minimum lethal dose. (Consult the Key's 

 discussion of Criterion 21. ) 



The maximum tolerated dose (coded in 

 the dosage fields, M, N, and P) can be 

 more specifically defined as: (a) maximum 

 tolerated concentration. Field M, (b) maxi- 

 mum tolerated quantity, Field N, (c) maxi- 

 mum tolerated duration of administration. 

 Field P. 



Note: If, in a group of individuals, test 

 data demonstrate the variation in and dis- 

 tribution of the individuals' maximum toler- 

 ances for the test compound (i. e. , several 

 MTD levels for each of which is determined 

 the percentage of individuals for which it 

 represents the MTD), use Criterion 51, 52, 

 or 53. 



When Criterion 21 is used, only Symbol 

 P or, when "death" is coded in Field T-2 

 (and then only under certain circumstances), 

 Symbol is used in Field W. Consult the 

 Code definitions and instructions for Sym- 

 bols and P of Field W. 



The greater the quantity of test compound 

 tolerated, the greater is the test 

 compound's rating as a safe therapeutic 

 agent. Therefore, code Field Y with the 

 same symbol coding the dose (Column 46 

 of Field M, Column 48 of Field N, or 

 Column 51 of Field P). 



22 Antagonism of the biological action of a 

 secondary compound. In other words, 

 dosage of the test compound needed to 

 prevent the test organism's demonstrated 

 response to the secondary compound alone, 

 when both compounds are administered 

 together. 



Note: Evaluation by Criterion 22 of a 

 test compound's ability as an antagonist 

 of the specific action of a given secondary 

 compound is not modified by the degree of 

 antagonism (i. e. , partial reduction of the 

 response to the secondary compound). 

 Criterion 22 should be used only when an- 

 tagonism of the secondary compound's 

 action has been totally prevented (100% 

 reduction of response to the secondary 

 compound). 



If, in a group of individuals, the data 

 reveal the variation and distribution of 

 antagonism ratio (see the evaluation of 

 antagonism. Field Y), use Criterion 55. 



Ratio: 



Evaluation of antagonism with Cri- 

 terion 22 is on the basis of the amount 

 of secondary compound antagonized 

 per unit of test compound. The greater 

 the amount of secondary compound 

 antagonized per unit quantity of 

 test compound, the greater is the 

 test compound's potency for antag- 

 onizing the action of that secondary 

 compound. 



Amount of secondary compound 



whose effect is antagonized 



100% (i.e., prevented) 



Minimum amount of test compound 



(antagonist) needed to antagonize the 



secondary compound's effect 100% 



The value from the calculation above 

 Is used to derive a code evaluation for 

 Field Y according to the following scale: 



1 <0. 05 thru 0. 05 



3 > 0. 05 thru 0. 5 



5 > 0. 5 thru 5 



7 > 5 thru 50 



9 >50 



187 - 



