FIELDS W, X, and Y 

 Columns 68; 69 and 

 70; and 71 



If the author expresses a threshold dose only as a range (e. g. , "the threshold response in the 

 single individual was with 20-30 rag" or "the threshold response in 50% of the organisms tested was 

 with 20-30 mg"), the CBCC codes that threshold dose in the dosage fields as being an average of 

 the extremities of the range and derives a Field Y rating directly from the coding of the dosage field 

 (Criterion 20) or through the Grid (Criterion 51, 52, or 53). 



A problem of definition accompanies Field Y ratings expressed as "minimum effective dose". 

 The problem derives from the ambiguity of the word "effective". Attention is called to Diagram A above, 

 in which are illustrated both the threshold dose (i. e. , the minimum dose producing the initial or lowest 

 level of response, tagged on Diagram A as dose level 2) and the minimum dose producing maximum 

 response (tagged as dose level 3 on Diagram A); each of these could be defined as minimum effective 

 doses, according to whether "effective" were interpreted as applying to "lowest or initial response" 

 (i. e. , threshold response) or to "maximum response". Indeed, beyond these two possibilities, an 

 author may consider any point of response between the actual minimum and maximum responses as the 

 point of adequacy for the specific use for which the compound is intended and define the dose producing 

 that level of response as being "effective". 



When dealing with specific responses that exhibit graduation of degree below the maximum 

 (i. e. , responses illustrated in Diagram A), the CBCC uses the term "minimum effective dose" to be 

 synonymous with "threshold dose" and CBCC coding and interpretation should be based on this defi- 

 nition of "minimum effective dose". 



If the author uses the expression "minimum effective dose" and it is described by the author 

 or otherwise recognized as being actually anything higher than threshold dose (e. g. , if it is the 

 minimum dose producing maximum response when maximum response is greater than threshold response) 

 a criterion other than Criterion 20 must be used. 



When dealing with responses of the type illustrated by Diagram B (i. e. , death or a response 

 of the "all-or-none" type), the expression "minimum effective dose" is not ambiguous when referring 

 to a test involving only a single individual's response; as the chart indicates, there is only one level 

 that the expression "minimum effective dose" could describe under these circumstances, since there 

 is essentially only one response level. However, tests involving such responses as Diagram B 

 illustrates frequently employ more than a single test individual, with the result that the data are 

 expressed as a minimum dose causing death (or an "all-or-none" type of response) in a given percentage 

 of individuals tested . Here, the expression "minimum effective dose" becomes an ambiguity, for the 

 concept of its definition may be according to one author the minimum dose killing one individual of 

 the group, e. g. , or it may be established for another author's data as the minimum dose killing 50% 

 of the individuals, or the minimum dose killing all individuals,' etc. On the assumption that when 

 the author is determining a "minimum effective dose" as a "minimum lethal dose" or as a "minimum 

 dose causing an 'all-or-none' response", the test was most reasonably devised to determine the dose 

 that would ideally (effectively) assure death or the "all-or-none" response in 100% of the group of 

 individuals, the CBCC has followed, for its coding, a definition of "minimum lethal dose" ("minimum 

 toxic dose") as the smallest dose that kills (or that causes the "all-or-none" type of response in) 100% 

 of the organisms tested. Therefore, when the expression "minimum effective dose" or "minimum lethal 

 dose" is used by the author with reference to a group or population and with no further explanation 

 about the actual per cent of organisms affected or killed, it should be interpreted as the smallest dose 

 killing 100%. Furthermore, since this dose causing response in 100% of organisms tested is demon- 

 strated to be the smallest dose capable of producing that degree of response, it can be correlated with 

 percent response on the Grid, using Criterion 51, 52, or 53; i. e. , the dose can be placed on the 

 abscissa of the Grid (at the 99. 99% level) and the Field Y code symbol will be the evaluation area of 

 the Grid in which the dosage falls. 



With reference to toxicity determinations of test compounds to be used therapeutically (refer to 

 Diagram B), note that when the author has determined a maximum dose not causing death (Dose Level 1 

 of the Diagram), he has had necessarily to determine the minimum dose causing death (Dose Level 2). 

 If the coder has available only the minimum dose causing death, he has no choice but to code it and 

 use Criterion 20 in Field X (or Criterion 51, 52, or 53, under circumstances described in the preceding 

 paragraph). When both levels are given in the author's data, however, the CBCC always prefers to 

 code Dose Level 1 and use Criterion 21 in Field X; while it is true that both of these dose levels reveal 

 the maximum safe level, Dose Level 1 is a more direct statement of this safe level than Dose Level 2. 



194 



