FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



an action of the compound (e.g. , "the test compound, by its presence, causes the test organism to 

 alter so that it can tolerate greater doses of the test compound"). If Criterion 18 is used in Field X, 

 Field T-2 would necessarily be coded with a symbol of the 51-- series (Symbol 512) rather than with 

 a symbol for any toxic response. However, a description, by the author, of the test compound's 

 specific toxic action would be expected with data describing tolerance increase and this should be 

 coded by constructing another biology code line, with Field T-2 coded with the symbol for the toxic 

 response and an appropriate Criterion other than Criterion 18 coded in Field X. 



Criterion 18 is intended for use when the author states the two tolerated dose levels which 

 are separated by a time interval. The ratio of the two doses provides a value to be fitted on a fixed 

 scale of the Code, from which scale is derived a code symbol. It expresses the comparative ability 

 of the test compound for becoming tolerated by the test organism (as compared to other toxic compounds) 

 or, in terms of the test organism, it expresses the comparative ability of the test organism to adjust to 

 the test compound (as compared to other test organisms' abilities to adjust similarly to the compound). 



In the individual test organism, this specific action is measured solely by the difference 

 between before-and-after dosage levels. This is the intensity to which the "action" occurs and the 

 dose level producing the tolerance is not considered a part of the expression of "potency" for in- 

 creasing the tolerance. (See Fields M and N, Specific Directions and Explanations, Division HA, 

 for a more complete discussion of coding procedures for tolerance increase. ) 



No criterion is proposed here for evaluating tolerance increase according to the incidence 

 of a given intensity of tolerance increase in a group of individuals. Criterion 62 might be used to 

 express the fact that, of a group of individuals, a given percentage demonstrated tolerance increase 

 of unspecified degree. 



B. Criterion 19: 



This criterion is for evaluation of the test compound's becoming "decreasingly tolerated by 

 the individual organism". I. e. , it evaluates the individual's increased sensitivity to the test compound, 

 when the author has determined the initial threshold dose and, after an interval, the final threshold dose 

 or the initial maximum tolerated dose and the final maximum tolerated dose. When these final doses 

 (final threshold or final maximum tolerated) are significantly lower than the initial doses, the measure- 

 ment is interpreted as evidence of increased sensitivity. 



As with Criterion 18, a code evaluation for Field Y is derived by the ratio of the two doses 

 (initial and final), fitted to a fixed scale. 



Neither Criterion 18 nor Criterion 19 have as yet actually been needed by the CBCC. They are 

 suggested here, however, as a means of evaluation when Field T is coded with "increase of tolerance" 

 (Field T-l, Symbol 1; Field T-2, Symbol 512) or with "increase of sensitivity" (i.e., "decrease of 

 tolerance", Field T-l, Symbol 2; Field T-2, Symbol 512) and when the values needed for the respective 

 ratios have been given by the author. 



14. Criterion 20; threshold dose or minimum effective dose; dose just larger than the maximum dose 

 which does not produce the specific response 



Criterion 2 might conceivably be regarded as a criterion relating intensity of response and size 

 of dose needed to produce that intensity, to provide a coordinate evaluation that would be an expression 

 of the compound's potency . This is suggested by the criterion's definition by which one of the two fac- 

 tors, response intensity, might be regarded as being fixed as a standard intensity, the threshold. This 

 would require making the assumption that any given response in a given test organism is apt to occur 

 at a standard threshold intensity, regardless of the compound inducing the response. However, since 

 it might well be argued that a response may vary widely in initial intensity according to test compounds' 

 characters and it might further be argued that the evaluation of a test compound should include consid- 

 eration of this initial intensity of response as well as the dose size initiating the response, evaluations 

 made by Criterion 20 should probably be regarded as no more an expression of potency (dose-intensity 

 coordinate) than Criterion 10 or 62, for example. In the case of "death" in the individual, any other 

 all-or-none response, or "death" defined to represent 100% kill of a population (see the second para- 

 graph following), when threshold intensity is by definition unvarying, Criterion 20 can legitimately be 

 regarded as giving a Field Y evaluation representing comparative "potency". 



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