FIELDS M and N 

 Columns 45 and 46; 

 47 and 48 



and N is the highest final dose to which the test organism was shown to be tolerant). In addition, 

 tolerance increase might conceivably be evaluated by Criteria 10, 11, 12, 13, etc. , when appropriate 

 time values are determined and are the author's basis for the test evaluation: duration of administration 

 needed to bring the organism's tolerance to the level indicated in Fields M and N or duration of the 

 increased tolerance level. 



If, however, the author were to have demonstrated a minimal dose which would initiate 

 or induce tolerance of the organism to the test compound, Field X is always coded with Criterion 20 

 (Threshold Dose), and Fields M and N are coded with that minimal dose. 



B. Sensitivity increase: 



The development of sensitivity of an organism to a test compound is understood to be essen- 

 tially the reverse of development of tolerance in that the organism becomes less tolerant to (i. e. , 

 becomes more sensitive to) the test compound by an initial exposure or exposures to the test compound. 

 This increased sensitivity is induced by an initial administration of the test compound. It is revealed 

 by a second or more doses in which a biological response appears which either did not occur with the 

 initial dose or which appeared to a greater degree than with the initial dose. As in the case of coding 

 increase-of-tolerance data, coding increase-of-sensitivity data depends on the test technique and the 

 way the evidence for a sensitivity increase or for production of a sensitive reaction is expressed. 



If the author merely states that the organism has developed an increased sensitivity or a 

 specific sensitive response to the test compound during a program of administration, code in Fields M 

 and N the lowest dose demonstrated to cause the sensitive reaction, code "causes increased sensi- 

 tivity" in the action fields ( T- I 2, T-2 51), and Criterion 01 in Field X. If there is determined a 

 measure of sensitivity production or sensitivity increase (i. e. , a new, lower maximum tolerated dose 

 after sensitization), it may be expressed as (l) an increase in response with each successive admin- 

 istration of the same dose (assuming that doses are spaced so that the response is evidence of 

 increased sensitivity) or (2) the appearance of a response after a second or more administrations of 

 the same dose . In this instance, Fields M and N are coded with the dose demonstrated to elicit the 

 sensitivity; Field X is coded with Criterion 01, if the exposure results in the initial appearance of a 

 sensitivity response or if the per cent increase in sensitivity response is unknown, or with Criterion 

 61 or 62, if the per cent increase in sensitivity response is known. The sensitivity production or 

 increase might also conceivably be expressed as a decrease in dosage necessary to maintain a 

 response of a given degree or decrease in dosage necessary to prevent a given response (i. e. , a 

 decrease in the threshold and maximum tolerated doses). In this case, Fields M and N are coded 

 with the lowest level to which this threshold dose or maximum tolerated dose has declined and Field X 

 is coded with Criterion 01, or, if the original and final dose levels are known, Criterion 19 may be 

 used. 



If the author should have demonstrated a minimum dose which will induce an increase of 

 sensitivity, that dose may be coded in Fields M and N with Criterion 20 in Field Y. Only in this 

 case should Criterion 20 be used with sensitivity data. 



Sensitization : The term "sensitization" is most often used in reference to a specific 

 immunological phenomenon as defined in the Code by Symbol 58. When the test organism is sensitized 

 to the test compound and Symbol 58 is used in Field T-2, Fields M and N are coded with the sensitizing 

 dose. The typical responses (allergy, anaphylactic shock, etc. ) to the test compound on subsequent 

 exposure are coded as such in Field T-2 and the dose coded in Fields M and N is the dose needed to 

 elicit these responses after sensitization. 



12. Dosage to be coded when the test compound is part of a formulation or when a mixture of 

 test compounds is administered 



The CBCC has avoided treating formulations as specific test compounds, for a number of 

 reasons. Therefore, when biology data are coded from tests using formulations, the single active 

 component of the formulation must be known. That single component is coded as the test compound, 

 Field B is coded with Symbol 6 (signifying that the compound is administered as part of a formulation, 

 but that the dose coded in Fields M and N and the evaluation are based on the test compound itself), 

 and Fields M and N are coded with the calculated amount of the test compound, not the amount of the 



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