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ASSESSMENT OF STANDARD REFERENCE COMPOUNDS FOR COMPARATIVE STUDIES USING THE SALMONELLA TYPHIMURIUM MUTAGENICITY ASSAY: II. WITH EXOGENOUS ACTIVATION
Citation:
Claxton, L., V. Houk, J. Warner, L. Myers, AND T. Hughes. ASSESSMENT OF STANDARD REFERENCE COMPOUNDS FOR COMPARATIVE STUDIES USING THE SALMONELLA TYPHIMURIUM MUTAGENICITY ASSAY: II. WITH EXOGENOUS ACTIVATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/265 (NTIS PB92113273).
Description:
The purpose of this project was to evaluate the variability in the mutagenic response of potential standard reference chemicals that require exogenous metabolic activation in the standard plate; incorporation Salmonella mutagenicity assay, and to develop ranking criteria for mutagenic activity based on these data. en indirect-acting mutagens were tested in two laboratories using Salmonella typhimurium TA100 and an Aroclor-induced rat liver S9. ach laboratory conducted four definitive testing rounds. ifferent batch of S9 was utilized for every two rounds. f the 10 chemicals tested, only 2-anthramine had a mean slope value greater than 1000. hree chemicals had slope values between 1000 and 100; and five chemicals had slope values between 100 and 10. he remaining compound, 9,10-dimethyl-1,2-benz(a)anthracene could not be placed into a single category because it had slope values on either side of 100 revertants per plate. oefficients of variance were low (i.e., below 25% in most cases). he low variability achieved in this study may be accounted for by two parameters of the study. irst, the amount of S9 was calibrated to a set amount of protein per plate (1.1 mg/plate) (not to a percentage of S9 in the S9 mix). econdly, the 10 test doses were placed in the initial, linear, nontoxic portion of the dose-response curves. he use of ten closely spaced, nontoxic doses allowed for a more accurate estimate of the slope. hese data, along with the data generated previously (Claxton et al., this volume) for 10 direct-acting chemicals, provide a basis for intralaboratory comparison and ranking of Salmonella mutagenicity data. oncurrent testing (same day, same laboratory, same technician, same bacteria, S9 and media) is a more acceptable method to control variance. owever, this is not always possible. he ability to quantify Salmonella mutagenicity data by the use of standard reference materials will ssist in potency comparisons of data generated in different laboratories or within the same laboratory on different days.