Evaluation of perfluorooctanoate for potential genotoxicity.

Perfluorooctanoate (PFOA) is a fully fluorinated eight-carbon fatty acid analog with exceptional stability toward degradation that has been used as an industrial surfactant and has been detected in environmental and biological matrices. Exposures to PFOA in the workplace and in the environment have continuously stimulated investigations into its potential human health hazards. In this article, the results of fifteen unpublished genotoxicity assays conducted with perfluorooctanoate (as either the linear or linear/branched ammonium salt (APFO) or the linear/branched sodium salt) are reported and include: seven mutation assays (three reverse mutation assays with histidine auxotrophic strains of , two reverse mutation assays with the tryptophan auxotrophic WP2uvr strain, one mitotic recombination (gene conversion) assay with D4, and an Chinese hamster ovary (CHO) HGPRT forward mutation assay); seven studies to assess potential for chromosomal damage (three CHO chromosomal aberration studies, an human whole blood lymphocyte chromosomal aberration study, and three mouse micronucleus assays); and an C3H 10T1/2 cell transformation assay. Although PFOA has not been demonstrated to be metabolized, all assays were conducted both in the presence and in the absence of a mammalian hepatic microsomal activation system. These assays were originally described in twelve contract laboratory reports which have been available the United States Environmental Protection Agency public docket (Administrative Record 226) for over a decade; however, the details of these assays have not been published previously in the open scientific literature. With the exception of limited positive findings at high and cytotoxic concentrations in some assay trials which reflected the likely consequence of cytotoxic disruption of normal cellular processes and not a specific genotoxic effect, the results of the studies presented in this paper and other published results clearly demonstrate the absence of direct mutagenic or genotoxic risk associated with PFOA. This finding is consistent with the physical/chemical characteristics of PFOA and is supported by other published genotoxicity studies.