COMPARISON OF RESPONSES OF BASE-SPECIFIC SALMONELLA TESTER STRAINS WITH THE TRADITIONAL STRAINS FOR IDENTIFYING MUTAGENS, THE RESULTS OF A VALIDATION-STUDY

The ability of a TA7000 series of Salmonella his(-) mutant tester stra ins to detect mutagens as classified by the traditional tester strains (TA100, TA98, TA1535, TA1537, TA97, TA102 and TA104) was evaluated us ing 30 coded chemicals, 5 of which were duplicates with different code numbers. The TA7000 series of tester strains were TA7001, TA7002, TA7 003, TA7004, TA7005 and TA7006, each of which reverts by a specific ba se substitution. In addition, each chemical was tested in a mixture of the base-specific strains (the Mix), plus the traditional strains, TA 98 and TA1537. A liquid version of the Salmonella mutagenicity assay w as performed in microtiter plates to allow partial automation for incr eased throughput. The results were compared to those in the National T oxicology Program (NTP) database, which were obtained from the traditi onal strains in the preincubation assay. In the two strains common to both protocols, TA98 and TA1537, the agreement was 80% and 85%, respec tively. When compared to the NTP results for TA100, the Mix gave a 72% concordance, while the addition of the frameshift tester strain, TA98 , increased the agreement to 76%. The overall agreement on positive or negative classifications of mutagenicity was 88% for the 25 chemicals tested. There were three notable exceptions to the overall agreement. Benzaldehyde was detected as a mutagen in TA7005 in contrast to its c lassification as a non-mutagen in the NTP database. This does not nece ssarily contradict the NTP results because the base-specific strains m ay respond to different mutagens. Two weak mutagens in the NTP databas e, 1-chloro-2-propanol and isobutyl nitrite, were not detected as muta gens in the base-specific new strains in the liquid protocol. While th ere are a number of major differences in the two assays, it was conclu ded that the results from each procedure are comparable. (C) 1998 Else vier Science B.V.