Mutation Research, 38 (1.976) 1--2 © Elsevier Scientific Publishing Company, Amsterdam - - Printed in The Netherlands
THE UTILITY OF SHORT-TERM TESTS F O R MUTAGENICITY FREDERICK J. DE SERRES Chief, Environmental Mutagenesis Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 (U.S.A.) (Received October 2nd, 1975) (Accepted October 2rid, 1975)
The Committee 17 Report on Environmental Mutagenic Hazards (February 14, 1975, pp. 503--514) discusses the need to screen environmental chemicals for mutagenic activity. During the past decade, exploratory experiments have indeed shown that mutagenic chemicals can be found in all major categories including food additives, drugs, pesticides and cosmetics, as well as household and industrial chemicals. However, only a limited number of chemicals have been tested from each category and the initial selection was most certainly biased. Thus, even though we know that there are mutagenically active compounds in each class, we have no data on their frequency. Obviously, more extensive testing will have to be done especially on agents with widespread environmental distribution. This need to test large numbers of environmental chemicals dictates some approach other than tests on whole animals because of their limitations in sensitivity and time as well as the extensive resources required. Short-term tests using microbial assay systems offer a practical solution to the problem of testing hundreds of chemicals rapidly and inexpensively. One of the primary objections against the utilization of microbes in the past has been concern over their ability to perform the same type of metabolic activation found in vivo in mammals. However, the recent development of in vitro techniques using preparations of liver microsomes [1] from various mammals (including man) has provided a new and effective approach for resolving this difficult problem. The high sensitivity of microbial assay systems coupled with in vitro techniques for metabolic activation provides an exciting new approach for toxicological evaluation. The field of environmental mutagenesis is rapidly evolving and our data base of c o m p o u n d s which have been thoroughly evaluated is extremely limited. It is important to keep in mind that much more work is needed to validate this approach and to determine the reliability of these newly developed assays. We still do n o t k n o w to what e x t e n t any of the short-term tests will produce false positives. In the Salmonella test [2] developed by Bruce Ames (University of California, Berkeley), for example, we still do n o t know to what extent reverse-
THE UTILITY OF SHORT-TERM TESTS F O R MUTAGENICITY FREDERICK J. DE SERRES Chief, Environmental Mutagenesis Branch, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 (U.S.A.) (Received October 2nd, 1975) (Accepted October 2rid, 1975)
The Committee 17 Report on Environmental Mutagenic Hazards (February 14, 1975, pp. 503--514) discusses the need to screen environmental chemicals for mutagenic activity. During the past decade, exploratory experiments have indeed shown that mutagenic chemicals can be found in all major categories including food additives, drugs, pesticides and cosmetics, as well as household and industrial chemicals. However, only a limited number of chemicals have been tested from each category and the initial selection was most certainly biased. Thus, even though we know that there are mutagenically active compounds in each class, we have no data on their frequency. Obviously, more extensive testing will have to be done especially on agents with widespread environmental distribution. This need to test large numbers of environmental chemicals dictates some approach other than tests on whole animals because of their limitations in sensitivity and time as well as the extensive resources required. Short-term tests using microbial assay systems offer a practical solution to the problem of testing hundreds of chemicals rapidly and inexpensively. One of the primary objections against the utilization of microbes in the past has been concern over their ability to perform the same type of metabolic activation found in vivo in mammals. However, the recent development of in vitro techniques using preparations of liver microsomes [1] from various mammals (including man) has provided a new and effective approach for resolving this difficult problem. The high sensitivity of microbial assay systems coupled with in vitro techniques for metabolic activation provides an exciting new approach for toxicological evaluation. The field of environmental mutagenesis is rapidly evolving and our data base of c o m p o u n d s which have been thoroughly evaluated is extremely limited. It is important to keep in mind that much more work is needed to validate this approach and to determine the reliability of these newly developed assays. We still do n o t k n o w to what e x t e n t any of the short-term tests will produce false positives. In the Salmonella test [2] developed by Bruce Ames (University of California, Berkeley), for example, we still do n o t know to what extent reverse-
