Genotoxicity Assessment of Chlorotrifluoroethylene Trimer Acid Using a Battery of In Vitro and In Vivo/In Vitro Assays

Abstract : Chlorotrifluoroethylene (CTFE) trimer acid, the perhalogenated fatty acid metabolite of the six-carbon oligomer of polychlorotrifluoroethylene (PCTFE), was evaluated in in vitro bioassays to assess its potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal mutagenicity assay, the Chinese hamster ovary (CHO) gene mutation assay, the CHO/sister chromatid exchange (SCE) and chromosome aberrations assays, the BALB/c-3T3 cell transformation assay and in vivo/in vitro unscheduled DNA (UDS) and S-phase synthesis assays. CTFE trimer acid did not demonstrate genotoxic potential in any of the in vitro assays and was also negative in the UDS assay. However, in the S-phase synthesis assay an increase in replicating cells was observed 16 hours after administration of CTFE trimer acid to the study animals by oral gavage. Interestingly, no increase in S-phase synthesis was observed at the standard assay time of 48 hours following dosing. This increase in S-phase synthesis indicated a rapid response to hepatotoxicity caused by CTFE trimer acid but the results of the test battery would predict no genetic risk from exposure.