Evaluation of perfluorooctanoate for potential genotoxicity

Abstract

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 In this article, the results of fifteen unpublished genotoxicity assays conducted with perfluorooctanoate (as either the linear or linear/branched ammonium salt (APFO) or the linear/branched sodium salt) are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 in vitro reverse mutation assays with histidine auxotrophic strains of Salmonella typhimurium, two in vitro reverse mutation assays with the tryptophan auxotrophic Escherichia coli WP2uvr strain, one in vitro mitotic recombination (gene conversion) assay with Saccharomyces cerevisiae D4, and an in vitro Chinese hamster ovary (CHO) HGPRT forward mutation assay); seven studies to assess potential for chromosomal damage (three in vitro CHO chromosomal aberration studies, an in vitro human whole blood lymphocyte chromosomal aberration study, and three in vivo mouse micronucleus assays); and an in vitro C3H 10T1/2 cell transformation assay. Although PFOA has not been demonstrated to be metabolized, all in vitro 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 via 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.

Genotoxicity assessment of perfluoroalkyl substances on human sperm

“…No genotoxicity was reported in HepG2 cells exposed to PFOA, PFOS, perfluorobutane sulfonate, PFNA, and PFHxA, in parallel to our results (Eriksen et al, 2010; Florentin et al, 2011). It was also concluded that PFOA did not show any direct mutagenic or genotoxic effect (Butenhoff et al, 2014). Unlike several studies in which similar negative results were obtained, the genotoxic effect was observed in HepG2 cells exposed to PFOA, PFHxS, PFOS, PFOA, and PFNA (Wielsøe et al, 2015; Yao and Zhong, 2005).…”

NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid, Perfluorooctanoic Acid, Perfluorononanoic Acid, and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

“…In a review of unpublished genetic toxicity test data generated in industry-sponsored studies, PFOA, tested as either an ammonium or sodium salt, was found to be negative in bacterial mutagenicity assays, in the CHO/HGPRT forward mutation assay, in the chromosomal aberration assay when performed using CHO cells or primary human lymphocytes, and in the mouse bone marrow micronucleus assay 99 .…”

Per- and polyfluorinated substances (PFASs): Environmental challenges

“…Little or no information is available for other long-F-chain PFASs. Numerous studies involving multiple assays found no direct mutagenic or genotoxic risk associated with PFOA, PFOS, PFBS and PFHxA [259][260][261].…”