FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



If a test compound characteristically produces the response in a large percentage of individuals 

 when administered in small quantities, its curve will fall on the upper left area of the Grid, whereas 

 if the test compound characteristically produces the response in a small percentage of individuals 

 when administered in large quantities, its curve will fall on the lower right area of the Grid. Therefore, 

 those compounds whose curves occur furthest to the lower right corner of the Grid are rated as the com- 

 pounds lowest in effectiveness (i. e. , the compounds having lowest potency ) and those whose curves 

 occur furthest to the upper left corner are rated as highest in effectiveness (highest potency). 



The total two-dimensional range from the left to right sides of the Grid (i. e. , the total area of 

 the Grid) has been divided into smaller ranges. A range on the lower right has been fixed as representing 

 low activity and a similar range on the upper left has been fixed as representing high activity. Between 

 these, the range fixed to represent intermediate activity has been further divided into three intermediate 

 ranges. To each of these ranges has been assigned a code symbol- -i. e. , a code rating, 9 representing 

 the higher activities, 1 representing the lower activities, and 3, 5, and 7 representing intermediate 

 activities. (Symbol 1 used with criteria employing the Grid is never used to code "no activity" or "no 

 response", as explained in Division 1. ) 



The lines dividing the Grid into five ranges are representative cumulative distribution curves 

 whose slopes, as well as their positions, are fixed as references for comparison. They accomplish 

 the purpose of establishing a standard or fixed reference by which one compound can be compared to 

 any other compound on the basis of their relative potencies for causing the same biological response 

 in the same test organism species. Although the division into ranges has been arbitrary to some degree, 

 the position and slope of the fixed reference lines dividing the Grid into the five areas were determined 

 as being reasonable from a study of a variety of actual test data. 



Beyond the general position on the Grid, it is not to be supposed that all distribution curves 

 for a given response are alike for all compounds. For example, a given test compound might produce 

 the specific response in a relatively high percentage of organisms at only a small dosage, yet by 

 increasing the dosage to many times the original quantity, the percentage of organisms responding 

 increases very little. This would be in contrast to another test compound which produces the specific 

 response in relatively few organisms at small dosages and when the dose is only moderately increased, 

 the percentage of organisms responding increases to a high level. The first compound's test results 

 would make a low, flat dose/percentage-organisms -responding curve; the second would make a steep 

 curve. Indeed, for any given response, no distribution curve for one compound should be considered 

 to be actually identical to the curve for any other compound. Therefore, not only will the position of 

 the curves plotted on the Grid vary from the exact position of the fixed reference lines (fixed curves) 

 of the Grid, but the slope of the plotted curves will almost invariably deviate from the slope of the 

 fixed lines. 



A code designation is made to modify any Grid-derived evaluation coded in Field Y when the 

 slope of the dosage/percentage-organisms-responding curve can be plotted and when, therefore, its 

 deviation one way or the other from the slope of the fixed reference lines (fixed curves) of the Grid is 

 known. This is explained in the following paragraph which, however, discusses first the situation in 

 which only one point or a fragment of the total cumulative distribution curve can be plotted. 



Frequently only a single dosage and the single response level produced by that dose are known. 

 In this case, the slope of the dosage/percentage-organisms-responding curve is unknown . It is known 

 that at that given dose, the specific response occurred in that given percentage of organisms and, 

 plotting these two factors on the Grid, the range in which it falls represents the code rating for that 

 compound at that dose level. This rating is comparable to ratings for all other compounds tested for 

 that specific action. It is only when a series of tests have been made using different doses in each 

 test that the dosage-response curve (transformed by the Grid to approach a straight line) can be plotted 

 and it can be seen how it varies from the fixed reference lines of the Grid. If the curve is more shallow 

 (i. e. , flatter or more nearly horizontal) than the fixed lines of the Grid, this fact is coded by Symbol # 

 (i. e. , the IBM 1 1 zone punch) in Field Y (Column 71 ), with the code rating. If the curve is steeper 

 (i. e. , more nearly vertical) than the fixed lines of the Grid, this fact is coded by Symbol * (i. e. , the 

 IBM 12 zone punch) in Field Y. Only one of the points on this curve which deviates from the slope of 

 the Grid's fixed lines is used to determine a code evaluation rating, the 50% -organisms -responding 

 point. The code designation of the deviation of slope from the slope of the fixed lines indicates 

 whether responses in more than 50% of the individuals (the upper half of the total cumulative distribution 



- 207 - 



