FIELDS W, X, and Y 



Columns 68; 69 and 

 70; and 71 



In any case, the relative merits of test compounds, for any given biological response, are ex- 

 pressed by this criterion solely on the basis of the relative size of the dose needed to produce this 

 standard response level. The especially desirable quality of the criterion and the rating it gives is 

 due to the fact that the level of response selected as a standard is a significant and experimentally 

 practical one, the first appearance of the given response (implying the lowest level of the response) 

 as the dose size is increased progressively from a level that did not cause the response. This is 

 referred to in most cases as the threshold of response and the dose level producing it is referred to 

 as the threshold dose . 



Some responses are essentially "all-or-none" (i. e. , the response either does not occur or, 

 when it is produced by a dose of sufficient size, it occurs at its maximum intensity); the most absolute 

 and conspicuous example of this is the phenomenon of death. When death is the biological response 

 of an individual organism, the word "threshold" is scarcely an appropriate term, since it carries the 

 implication that the response's initial appearance can be followed by a greater degree of response and 

 this, in the case of death of the individual and any other "all-or-none" type of response, is impossible. 

 Nevertheless, frequently a laboratory test determines the lowest dose which causes death or some other 

 "all-or-none" response. Criterion 20 must be used for rating the compound according to the minimum 

 quantity (or maximum dilution or minimum duration of administration) needed to produce death or any 

 response which is, like death, "all-or-none". This is conveniently referred to as the "minimum effec- 

 tive dose", an expression which at least has the virtue of avoiding the definite implication that the 

 response might occur to a greater degree if a greater quantity of compound were administered. 



Avoiding the implications of the term "threshold", as pointed out above, and the ambiguities of 

 the word "effective" (see the ninth and subsequent paragraphs of this division), Criterion 20 can best 

 be defined as the criterion which bases an evaluation on the dose which is just greater than the highest 

 dose which does not produce the response coded in Field T. The following diagrams illustrate the use 

 of Criterion 20, as well as of Criterion 21, relative to responses as they occur in the individual organ- 

 ism. (I. e. , the diagrams are only intended to illustrate responses of one individual of the species 

 tested, not of a population or group of individuals of the species tested. ) 



Diagram A Is concerned 

 with any specific response 

 that exhibits graduation of 

 degree below maximum. 

 The horizontal dose line 

 does not represent a con- 

 tinuous application, but 

 merely Increasing size of 

 dose; any single point on 

 the dose line represents a 

 single dose of determined 

 size. Neither does the 

 response line represent a 

 single response in an 

 organism, but any single 

 point represents the level 

 to which the response 

 would rise corresponding 

 to the size of any single 

 dose on the dose line. 



Diagram B is concerned 

 with death as the specific 

 response or with a response 

 that exhibits no graduation 

 of degree below maximum 

 (an "all-or-none" type of 

 response). The dose line 

 and the response line are 

 as described above for 

 Diagram A. 



DIAGRAM A 



Beginning of 

 response; mini' 

 mum response 



No response 



(Criterion 01) 



(Field W: Symbol J) 



Gradually in- 

 creasing degree 

 of response 



r° 



* — (Increasing dose size) 



Maximum dose not 

 producing the re- 

 sponse (Criterion 

 21) (Field W: 

 Symbol P) 



Threshold dose 

 (Criterion 20) 

 (Field W: 

 Symbol P) 



Minimum dose producing 

 maximum response. 

 (Criteria 01, 02, 10, 12, 

 52, 62, e.g. ) (Field W: 

 Symbol 0) 



Doses not minimal 

 producing maximum 

 response. (Criteria 

 01, 02, 10, 62, e.g. ) 

 (Field W: Symbol N) 



DIAGRAM B 



Death or the 



beginning of 



an "all-or-none" 



type of response 



No response 



(Criterion 01) 



(Field W: Symbol L) 



Maximum level of 

 'all-or-none" response 



Response 



' — (Increasing dose size) 



UL 



Maximum dose not 

 causing death (the 

 maximum tolerated 

 dose), or not 

 causing a response 

 of the "all-or-none' 

 type. (Criterion 21) 

 (Field W: Symbol 0) 



UL 



Minimum dose causing 

 death (the minimum 

 toxic dose) or the 

 minimum dose causing 

 a response of the 

 'all-or-none" type 

 (minimum effective 

 dose). (Criterion 20) 

 (Field W: Symbol 0) 



3: 



_EL 



Doses causing death 

 or causing the response 

 at the maximum level. 

 (Criterion 01, 02, 11, 

 52, 62. e.g.) (Field W: 

 Symbol M) 



192 - 



