FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



definition of Criterion 17. The evaluations made by Criterion 17, nevertheless, are essentially only 

 meaningful when studying coded information on compounds tested by this method. (A CBCC code 

 evaluation based solely on a percentage difference between amounts of treated and untreated food 

 consumed might have been preferable, using Criteria 61 and 62 or a special criterion, leaving interpre- 

 tation of that differential, as to its significance as a repellent, to an entry in the written abstract 

 accompanying the coding or providing a second coding area for evaluation according to the author's 

 concepts. ) 



The person using the coded files for purposes of comparative repellency studies will need to 

 refer to the Biology Code Sheets in the case of those compounds coded with Criterion 17 in Field X 

 with Symbol 1 in Field Y , in order to study the actual comparative consumption of treated food. For 

 this reason, the coder should always include in the written abstract of the code line, in addition to 

 the actual index, the measurements made from the test, if given by the author- -i. e. , the amount of 

 treated food consumed per day, the amount of untreated food consumed per day, the weight of the 

 animal, the amount of the test compound consumed, etc. 



If the rats exhibited no preference (when as much treated food was consumed as untreated food), 

 indicating actual inactivity of the compound as a repellent, Criterion 01 should be used with Symbol 1 

 in Field Y, and Field W should be coded with Symbol K (or with Symbol J if the dose of 2% were stated 

 to be the maximum tolerated). 



When coding repellency data from tests using the standard dose of 2%, Field W should be 

 coded with Symbol L (unless the 2% level should have been demonstrated to be the maximum tolerated 

 dose, when Symbol M should be used, or unless it should have been demonstrated by additional testing 

 to be the minimum dose causing the greatest response, when Symbol should be used), since the 

 single dose level administered by the standard testing procedure does not demonstrate whether smaller 

 doses would cause the same or less repellency. 



13. Criterion 18 (Tolerance Increase) and Criterion 19 (Sensitivity Increase ) 



A. Criterion 18: 



This criterion is for expressing the degree to which an individual organism has adjusted to a 

 test compound over a period of time so that the original sensitivity of the organism to the compound is 

 diminished; i. e. , the organism's tolerance for the test compound has increased. Coding of this increase 

 of tolerance is discussed in Fields M and N (Division 1 1A of the Specific Directions and Explanations 

 of Fields M and N), but the provision made for it is reviewed here briefly. 



For measurement of tolerance increase in the test organism, the intensity of toxic response, 

 in the case of Criterion 18, is fixed by definition at the same point as with Criterion 21. This intensity 

 is defined for Criterion 21 as a negative level: i. e. , the organism's unresponsiveness which immediately 

 precedes the organism's response as the dose size is increased. (See Division 15. ) Therefore, like 

 Criterion 21, the potency of a drug for causing this toxic effect is expressed adequately in terms of the 

 dose size. 



The reduction of sensitivity in the individual is expressed sometimes as "tolerance develop- 

 ment" rather than "tolerance increase", or as a decrease in sensitivity of the organism, or as an "in- 

 crease in resistance to the test compound" or as "increase in, or production of, refractoriness" to the 

 compound. Regardless of the expression used, the phenomenon is demonstrated only by determining the 

 minimum initial dose level that is toxic to the individual organism and, after an appropriate interval, the 

 minimal final dose level that is toxic to the same individual. Increased tolerance is demonstrated when 

 the final tolerated dose level is significantly greater than the initial tolerated dose level. Inasmuch as 

 this phenomenon occurs in the individual organism, the toxic effect is some toxic symptom other than 

 death, because death in the individual precludes determining subsequent tolerated quantities of the test 

 compound. 



As was suggested by the first statement of this discussion of Criterion 18, the evaluation 

 expressed by the criterion may be regarded as an evaluation of the test organism's ability to adjust to 

 the test compound, rather than an evaluation of any specific action of the test compound. Only by 

 stretching the concept of the "specific action" can tolerance to the test compound be considered as 



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