FIELD T-2 

 Columns 58, 59, 60, and 61 



In the situation in which the test compound is administered with a second compound whose 

 carcinogenic ability when administered alone has been demonstrated, in order to determine the test 

 compound's effect on the carcinogenic ability of the second compound, no tumor exists at the time of 

 administration. The action of the test compound is not on a tumor, therefore, but is on the candidate 

 carcinogenic action of the secondary compound, Field T-l is coded with Symbol 8, 9, or C, and Field 

 T-2 is coded with Symbol 43. 



20. Symbols of the 51-- series; tolerance 



General use of Symbols 51, 511, 512, and 513 vs. Symbols 514 and 5131; 51-- series vs. Symbol 5S 

 Symbols 51, 511, 512, and 513 are used to code the phenomenon whereby the test organism 

 develops a tolerance to the test compound through administration (usually repeated administration) of 

 the test compound. This is discussed in the Key in Fields M and N (Division 1 1 of Specific Directions 

 and Explanations for Fields M and N). The original specific chemical effect (diminishing with any tol- 

 erance development) is coded in Field T-l and T-2 by another code line . (See the Specific Directions 

 and Explanations for Field G, Division 11. ) The basic distinctions between the definitions for Symbols 

 51, 511, 512, and 513 are made in the Code. The test compound's "action" (the development of 

 tolerance) is coded in Field T-l as an increase over the level of tolerance existing at first exposure to 

 the test compound (Symbol 1 of Field T-l). Symbol 2 of Field T-l is used with Symbols 51, 511, 512, 

 and 513 to indicate a decrease of tolerance (i. e. , to code a production of [increase of] sensitivity). 

 With these Field T-2 symbols, Symbol 8, 9, A, or C is used in Field T-l to code the test compound's 

 effect on the increase or decrease of tolerance to a secondary compound due to administration of the 

 secondary compound. To code an increase or decrease of tolerance to a secondary compound due to 

 administration of the test compound, use Symbol 514 or 5131. "Sensitization" is defined as a specific 

 phenomenon distinct from increase of sensitivity and is coded by Symbol 58. 



Symbol 511 : 



Symbol 51 1 is used for coding the production of a tolerant race of the test organism (tolerant 

 to the test compound ) due to exposure to the test compound. (This does not necessarily imply either 

 genetic mutation by the test compound nor the survival of naturally occurring tolerant individuals; it 

 implies only that exposure to the test compound results in tolerant individuals whose tolerance to the 

 test compound is inheritable. ) Only Symbol 1 in Field T-l is used to code the increase in inheritable 

 tolerance. Use Symbol 2 in Field T-l to code the decrease in inheritable tolerance (i. e. , the production 

 of a race with increased sensitivity). Use Symbol 8, 9, A, or C in Field T-l to code the test compound's 

 effect on the increase or decrease of inheritable tolerance to a secondary compound due to exposure to 

 the secondary compound. To code an increase or decrease of an individual's tolerance of a secondary 

 compound due to administration of the test compound, use Symbol 514 or 5131. 



Symbols 513 and 5131 : 



Symbol 513 is used for coding the increase in tolerance to the test compound due to admin- 

 istration (usually repeated) of the test compound at a dosage level considerably below the level produc- 

 ing the effect for which tolerance is developed. Use only Symbol 1 in Field T-l with Symbol 513, since 

 the term tachyphylaxis is used to imply increase in tolerance and never a decrease. Use Symbol 8, 9, 

 A, or C to code the effect of the test compound on the increase of tolerance to a secondary compound 

 due to tachyphylactic administration of the secondary compound. To code the increase in tolerance to 

 a secondary compound due to tachyphylactic administration of the test compound, use Symbol 5131. 



Symbol 514 : 



Use only Symbol 1 of Field T-l to code the increase in tolerance to the secondary compound. 

 (Symbol 514 is limited to use for coding "cross-tolerance" and therefore is not used with Symbol 2 in 

 Field T-l. ) Use Symbol 8, 9, A, or C to code the test compound's effect on the increase in tolerance 

 to a third compound caused by administration of a secondary compound (the third compound can only be 

 written in Field D). 



21. Symbols of the 5C- series; resistance of the host to a pathogen, tumor, or non-infectious pathology 



Reference to symbols of the 51-- series will reveal that they code the development of tolerance 

 for (resistance to) the test compound or a secondary compound , by the organism to which administration 

 was made. 



146 - 



