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EC number: 228-193-9 | CAS number: 6163-58-2
The objective of this study was to determine the potential of Tri-o-tolylphosphine and/or its metabolites to induce reverse mutations at the histidine locus in several strains of Salmonella typhimurium (S. typhimurium; TA98, TA100, TA1535, and TA1537), and at the tryptophan locus of Escherichia coli (E. coli) strain WP2uvrA in the presence or absence of an exogenous mammalian metabolic activation system (S9). The test was performed in two independent experiments, at first a direct plate assay was performed and secondly a pre-incubation assay. The study procedures described in this report were based on the most recent OECD and EC guidelines. Batch B64002 (Pfizer Lot no. 2000850599) of Tri-o-tolylphosphine was an off-white crystalline powder. The vehicle of the test item was dimethyl sulfoxide. In the dose-range finding study, the test item was initially tested up to concentrations of 5000 µg/plate in the strains TA100 and WP2uvrA in the direct plate assay. The test item was tested up to or beyond a precipitating dose level. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed. In the first mutation experiment, the test item was tested in the strains TA1535, TA1537 and TA98 up to concentrations of 512 and 5000 µg/plate in the absence and presence of S9-mix, respectively. The test item precipitated on the plates at dose levels of 164 and 1600 µg/plate and upwards in the absence and presence of S9-mix, respectively. The bacterial background lawn was not reduced at any of the concentrations tested and no biologically relevant decrease in the number of revertants was observed.
In the second mutation experiment, the test item was tested in the tester strains TA1535, TA1537, TA98, TA100 and WP2uvrA in the pre-incubation assay up to concentrations of 512 and 1600 µg/plate in the absence and presence of S9-mix, respectively. The test item precipitated on the plates at dose levels of 512 µg/plate and upwards. Cytotoxicity, as evidenced by a reduction of the bacterial background lawn, was observed in all Salmonella typhimurium tester strains in the absence of S9-mix. In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. The test item did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment. In conclusion, based on the results of this study it is concluded that Tri-o-tolylphosphine is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
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