FIELDS W, X, and Y 



Columns 68, 69 and 



70; and 71 



Individuals responding is not an expression of potency which is defined in Division 8 as a correlation 

 of dose size and intensity of response. 



The CBCC has devised no coding criterion for correlating intensity of the action in terms of 

 time values (duration of action, time to specific action, etc. ) with the intensity of response in terms 

 of percentage of response in the individual organism (e. g. , "Compound A caused 10% increase in 

 blood pressure for 30 minutes", or "Compound B caused 10% increase in blood pressure for 2 hours", 

 or "Compound C caused 50% increase in blood pressure for 30 minutes"). 



Criteria 54, 57, 58, and 59 can be used when the data consist of the incidence (in a group of 

 organisms) of a given time value (a duration of action, a time of specific action, etc. ) at one given 

 dose level--or of the incidence of each of several time values (several durations of action, e.g.) at 

 one given dose level. For example: "In 25% of the individuals administered 50 mg/kg, the response 

 lasted 5-10 minutes; in 40% of the individuals (administered that same quantity of test compound), 

 the response lasted 10-20 minutes; in 20%, the response lasted 20-25 minutes; and in 15%, it lasted 

 more than 25 minutes". To derive a code evaluation from these data, the Grid is used, plotting on it 

 the several coordinates (the several durations of response with the cumulative percentages of organisms 

 responding for each duration). The following outline for the example above will be helpful as a general 

 illustration of the use of the Grid for evaluation by those four criteria. In this particular example, 

 Criterion 54 would be used. Note also that when using Criterion 54, the reciprocal of the symbol 

 coded in Column 66 of Field U is used as the value plotted on the abscissa of the Grid. This is 

 explained in Division 8 of the Specific Directions and Explanations of Field U. 



Duration Symbol for duration Symbol for use Cumulative percentage of individuals 



of of response in on the ordinate showing duration of response. The 



Response Column 66 (Field U) of the Grid response endured for: 



5-10 min. 4 (Scale 4) 6 at least 5-10 minutes in 100% of 



individuals 



10-20 min. 5 (Scale 4) 5 at least 10-20 minutes in 75% of 



individuals 



20-25 min. 6 (Scale 4) 4 at least 20-25 minutes in 3 5% of 



individuals 



>25 min. 6 (Scale 4) 4 more than 25 minutes in 15% of 



individuals 



On the Grid, the position and slope of the distribution curve, shown by a line connecting the 

 four coordinates of this example, indicates the evaluation to be coded in Field Y, according to the 

 area of the Grid in which it falls. Evaluations of all compounds tested for a given action and evaluated 

 by Criterion 54 tend to be comparable by virtue of the fact that those evaluations were made with 

 reference to the same fixed areas of the Grid. If the curve occurs on the right hand side of the Grid, 

 a low intensity of response is indicated (note again that this is not an expression of "potency", since 

 the dose size is not correlated here); the further the curve occurs toward the left edge of the Grid, the 

 higher the intensity of response is indicated to be. However, relative to this evaluation, reference 

 should be made to the fifth and sixth paragraphs of Division 10, pointing out that evaluations of Criterion 

 10, 11, 12, and 13 are largely dependent on the coder's judgment in selecting an appropriate scale in 

 Field U; this factor plays the identical role with Criteria 54, 57, 58, and 59. The positions of the 

 curve on the Grid (right or left) is dependent on the coder's choice of scale in Field U. 



The following sample data illustrate for each of the four criteria the way the cumulative per- 

 centage of organisms responding is plotted on the Grid to derive an evaluation of the intensity of 

 response to the dose administered and coded in Fields M, N, O, and P. 



Criterion 54: 30 minutes after the response began, it had ceased in 80% of the individuals to which 

 the test compound had been administered at the coded dose; 50 minutes after the 

 response began, it had ceased in 100% of the individuals. Here, 80% and 100% 

 (99. 99%) represent the points to be plotted on the ordinate of the Grid. The reciprocal 

 of the value coded in Column 66 of Field U is to be plotted on the abscissa. 



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