FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



On the other hand, when compounds are being tested for their ability to kill (i. e. , not tested 

 for therapeutically safe levels), the CBCC always codes the dose revealing best the compound's 

 killing potency . This is always Dose Level 2 of Diagram B. 



When a biology code line is made to record a chemical's threshold or minimal effective dose, 

 there is no question about the specific response of Field T having been produced nor about the dose 

 being the minimum necessary to cause that particular intensity of response. Therefore, when Criterion 

 20 is used in Field X, Field W is always coded with Symbol P or (never with Symbol M, since this 

 symbol is used to indicate that the minimum dose needed has not been demonstrated, nor with Symbols 

 L or N which are used only when the minimum response intensity has not been determined, nor with 

 Symbols J, K, or Q which indicate that the response was not produced or was produced only 

 questionably). 



15. Criteri on 21; maximum tolerated dose; largest dose not producing the response in Field T 



In the case of Criterion 21, the fixed level of intensity of response in the individual organism 

 is negative- -i. e. , non-response: the organism's unresponsiveness which immediately precedes the 

 organism's response as the dose size is increased. With this fixed definition of the response level, 

 the size of the dose becomes the only variable and it is this dose size (coded in Field M, N, or P) on 

 which is based the Field Y rating when Criterion 21 is used. 



This criterion is almost restricted in use to the experimental determinations of maximum safe 

 levels of chemicals to be used therapeutically. This is discussed in the two paragraphs before the 

 last, in Division 14. (See the dose level tagged as 1 of Diagram B, Division 14. ) 



However, Criterion 21 might also be used, as indicated in Diagram A (dose level tagged as 1) 

 of Division 14, when a maximum dose has been determined which does not cause some response other 

 than death (ordinarily some non-lethal toxic response). 



When the maximum dose not producing the response (death or otherwise) is determined in 

 individual organisms, Field Y is coded with the dosage rating coded in Column 48 of Field N (or 

 Column 46 of Field M or Column 51 of Field P). The code value of Column 46, 48, or 51 is trans- 

 ferred directly to Field Y as the Field Y rating (rather than inversing it as in the case of Criterion 20). 

 The reason for this is explained as follows. 



When Criterion 21 is used, Field T is always coded with the action that is produced (e. g. , 

 "death") when a dose is administered that is larger than the dose coded in Field M, N, or P; this 

 Field T coding is desirable in view of the fact that the compound's specific action (e. g. , its toxic or 

 lethal quality) had to be demonstrated in order to determine the maximum dose that did not produce the 

 action (e. g. , a maximum tolerated dose). At the same time, note that, according to the CBCC coding 

 pattern, when a dose that did not produce the action. in Field T is coded in Fields M, N, and P, the 

 failure to produce the response with that dose is always indicated in Field Y by Symbol 1, with Criterion 

 01, 02, or 62. These coding conventions represent a problem for Criterion 21, since (1) it is desirable 

 to have coded in Field T the action (usually "death") which has actually been demonstrated in the 

 process of determining the maximum dose that did not produce it, yet (2) it is the intention of the 

 criterion to give a rating to the compound according to that largest dose that did not cause the action 

 which means that Fields M, N, and P should be coded with that non-active dose level. The solution 

 lies with the definition of the criterion; contrary to every other criterion of Field X, the definition for 

 Criterion 21 implies that the action coded in Field T was produced but only when a dosage higher than 

 the dose coded in Field M, N, or P is administered. Thus, having Criterion 21 in Field X carries the 

 implication that the response in Field T did not occur at the coded dose level. The criterion then pro- 

 ceeds to rate the test compound, not on its ability to produce the response, but on its ability not to 

 produce the response, a rating as unique in Field Y as the dose is unique in Fields M, N, and P, 

 relative to the action coded in Field T. Consider, to illustrate the Field Y coding, the response, death 

 (Field T), for which has been determined the largest dose not producing it (i. e. , the maximum tolerated 

 dose): the smaller the maximum tolerated dose, the greater is the compound's toxic potency; the 

 greater the toxic potency, the less is the compound's ability not to kill (i. e. , the less is it safe). 

 Therefore, it can be seen that the smaller the maximum tolerated dose, the smaller is the ability not 

 to kill- -a direct rather than an inverse relation. Thus, when Criterion 21 is used, the coding in 

 Field M, N, or P is used directly to rate the compound's ability not to produce the action in Field T. 



195 - 



