FIELDS W, X, and Y 



Columns 68; 69 and 



70; and 71 



Field W makes another basic distinction, in addition to the one just discussed, which Fields X 

 and Y are incapable of making; this one also is related to the dose level administered in the test whose 

 results are being coded, but it concerns positive data (i. e. , tests demonstrating that the chemical CAN 

 produce a given response). The following brief review of response levels and dosages related to those 

 levels will be helpful in understanding the use of Field W symbols, L, M, N, 0, and P. 



Positive response may be in terms of either (1) an intensity of response of the individual organism 

 or (2) an intensity of response expressed as the number of individuals , of a group, responding at a spec- 

 ified response level (e.g. , the number responding by showing a threshold decrease in blood pressure, 

 or 10% increase in growth rate, or cure [ 100% relief], or death ). In either case, a given test compound 

 may cause the maximum intensity of response of which the individual or percentage of individuals of the 

 test organism species is capable of making. On the other hand, regardless of the quantity administered, 

 another test compound may be capable of causing only an intensity of response that is lower than the 

 response the species is capable of making. These aspects of a test compound's action are significant 

 in evaluating its ability to cause the biological response- -the ultimate intensity to which the test 

 compound can induce the response (which may be equal to or much lower than the intensity of response 

 the organism is capable of making) and the minimum size of the dose needed to cause that greatest 

 response intensity. 



Ideally, for each compound tested for each specific action, it might be desirable to have infor- 

 mation, for the individual , about both the maximum response intensity which the test compound is cap- 

 able of inducing and the minimum dose needed for that maximum intensity, as well as information about 

 threshold intensity and dose. In addition, it might be desirable to know, for each compound and action, 

 the maximum percentage of individuals the test compound can effect, when administered to a population , 

 and the minimum dose needed to affect that number of individuals, as well as information about the 

 smallest number (threshold number) responding to any dose. 



All this information is seldom determined or available for any one test compound, because it 

 can ordinarily be determined only by running several tests at different dosage levels, in addition to the 

 specific test being coded; nevertheless, certain types of tests are commonly performed as a series to 

 determine one or more specific levels of response and the minimum doses causing each. 



Between the dose causing the chemical's maximum action and the threshold dose, the intensity 

 of response is generally directly proportional to the size of the dose. This direct relationship between 

 threshold dose and threshold response, between doses and response intensities above threshold, and 

 between maximum response of which the compound is capable and minimum dose causing that maximum 

 response is significant. Whether an evaluation is composited by relating the two factors, dose vs. re- 

 sponse intensity, or whether evaluation is based solely on intensity of response with the dose causing 

 that intensity coded in Fields M, N, and P, the dose coded in Fields M, N, and P should ideally have been 

 determined by the author to be the minimum dose causing whatever intensity of response is being coded. 

 If not, the evaluation should not be based on the dosage used or Field W should be coded to indicate 

 the fact that the dose was not known to be minimum. 



Field W has been furnished with five symbols, L, M, N, 0, and P, which permit distinguishing 

 whether the response coded in Field T is or is not demonstrated to be the maximum response which the 

 test compound is capable of producing and whether the dose causing the response (coded in Field M or 

 N) is or is not demonstrated to be the minimum dose needed to cause that particular intensity on which 

 the evaluation in Field Y is based. This is information either supplied by the author or evidenced by 

 one or more tests prior to the test which is being coded. 



It must be kept in mind that any test compound may, in addition to the response desired, cause 

 other responses. If the desired response is non-toxic (therapeutic or regulatory, e.g. ) and if, in 

 addition, the test compound causes death or non-lethal toxic effects, the therapeutic or regulatory re- 

 sponse can be produced only to the intensity that the dose size causing that intensity also causes death 

 or other toxic response. In other words, toxicity of a compound may place a ceiling on the dose size 

 that can be administered and on the maximum intensity of non-toxic response; this ceiling may be below 

 the theoretical point of maximum intensity of non-toxic response the organism might make barring the 

 toxicity. 



Many chemical-biological test data are concerned with only a single test using only a single 

 dose level. Therefore, much coding in Field W Indicating that the response of Fields T- 1 and T-2 



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