Mutation Research, 168 (1986) 69-240 Elsevier 69 MTR 07208 The Salmonella typhimurium/mammalian microsomal assay A report of the U.S. Environmental Protection Agency Gene-Tox Program * L.E. Kier ‘, D.J. Brusick 2, A.E. Auletta 3, E.S. Von Halle 4, M.M. Brown 4, V.F. Simmon 5, V. Dunkel 6, J. McCann 7, K. Mortelmans *, M. Prival 6, T.K. Rao 9 and V. Ray lo. ’ Monsanto Co., St. Louis, MO; 2 Hazleton Biotechnoiogies Corp., Kensington, MD; ’ U.S. Environmental Protection Agency, Washington DC; ’ Environmental Mutagen Information Center, Oak Ridge National Laboratory **, Oak Ridge, TN; 5 W.R. Grace and Co., Columbia, MD; ’ Food and Drug Administration, Washington, DC; 7 Lawrence Berkeley Laboratory, Berkeley, CA; ‘SRI International, Menlo Park, CA; 9 Integrated Laboratory Systems, Research Triangle Park, NC; ” Pfizer, Inc., Groton, CT. (Received 25 April 1986) (Accepted 15 May 1986) zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI Contents I. Introduction . . . . . . . . . . . . . . . . . . . A. Historical Background . . . . . . . . . . . . . . . . . . B. Salmonella Test Strains - Genetic Basis of the Test . . C. Assay Implementation ..................... . D. Assay Techniques ........................ II. Methods ................................. A. Selection of the Data Base .................. B. Evaluation of the Data Base ................. 1. Criteria for Positive and Negative Test Responses 2. Special Situations ...................... III. Results .................................. A. Table of Results ......................... B. Discussion of Results ..................... IV. Interpretation of the Data Base ................. A. Correlation of Mutagenicity and Carcinogen&city Results 1. Table of Results ........................... 2. Discussion of Results ....................... B. Mutagen Prediction ........................... . . . . . . ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ...... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... ......... 70 70 72 73 73 74 74 75 75 75 182 182 183 217 217 217 225 228 * Work Group Report prepared for the Gene-Tox Program (Office of Toxic Substances, Office of Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC). The authors are members of the Gene- Tox Work Group on Salmonella typhimurium. ** 0 P erated by Martin Marietta Energy Systems, Inc., under contract DE-AC05-84OR21400 with the U.S. Department of Energy. 80-D-X0953 to the Oak Ridge National Laboratory, it has not been subjected to the Agency’s required peer and policy re- view, and therefore, does not necessarily reflect the views of the Agency and no official endorsement should be inferred. The protocols stated, suggested use of the assay in a screening program, and research recommended should not be taken to represent Agency policy on these matters. Although the review described in this article has been funded wholly or in part by the U.S. Environmental Protection Agency through the interagency agreement DOE 40-1123-80, EPA No. By acceptance of this article, the publisher or recipient acknowledges the U.S. Government’s right to retain a nonex- elusive, royalty-free license in and to any copyright covering this article. 0165-1110/86/SO3.50 0 1986 Elsevier Science Publishers B.V. (Biomedical Division)