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      A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and cancer risk in humans

      , , , , ,
      Critical Reviews in Toxicology
      Informa UK Limited

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          Abstract

          Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are ubiquitous synthetic chemicals with no known effect on human cancer development. This article systematically and critically reviews the epidemiologic evidence regarding the association between PFOA and PFOS exposure and cancer risk in humans. Eighteen epidemiologic studies - eight of PFOA, four of PFOS, and six of both PFOA and PFOS - have estimated associations of exposure to these chemicals with cancer incidence or mortality, with studies equally divided between occupational and nonoccupational settings. Although some statistically significant positive associations have been reported, for example, with cancers of the prostate, kidney, testis, and thyroid, the majority of relative risk estimates for both PFOA and PFOS have been between 0.5 and 2.0 (with 95% confidence intervals including 1.0), inconsistently detected across studies, counterbalanced by negative associations, not indicative of a monotonic exposure-response relationship, and not coherent with toxicological evidence in animals, in which the primary target organs are the liver, testis (Leydig cells), and pancreas (acinar cells). Many positive associations with PFOA exposure were detected in community settings without occupational exposure and were not supported by results in exposed workers. Given that occupational exposure to PFOA and PFOS is one to two orders of magnitude higher than environmental exposure, the discrepant positive findings are likely due to chance, confounding, and/or bias. Taken together, the epidemiologic evidence does not support the hypothesis of a causal association between PFOA or PFOS exposure and cancer in humans.

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          Most cited references78

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          Perfluoroalkyl and Polyfluoroalkyl Substances in the Environment: Terminology, Classification, and Origins

          The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and harmonize communication on PFASs by offering terminology for use by the global scientific, regulatory, and industrial communities. A particular emphasis is placed on long-chain perfluoroalkyl acids, substances related to the long-chain perfluoroalkyl acids, and substances intended as alternatives to the use of the long-chain perfluoroalkyl acids or their precursors. First, we define PFASs, classify them into various families, and recommend a pragmatic set of common names and acronyms for both the families and their individual members. Terminology related to fluorinated polymers is an important aspect of our classification. Second, we provide a brief description of the 2 main production processes, electrochemical fluorination and telomerization, used for introducing perfluoroalkyl moieties into organic compounds, and we specify the types of byproducts (isomers and homologues) likely to arise in these processes. Third, we show how the principal families of PFASs are interrelated as industrial, environmental, or metabolic precursors or transformation products of one another. We pay particular attention to those PFASs that have the potential to be converted, by abiotic or biotic environmental processes or by human metabolism, into long-chain perfluoroalkyl carboxylic or sulfonic acids, which are currently the focus of regulatory action. The Supplemental Data lists 42 families and subfamilies of PFASs and 268 selected individual compounds, providing recommended names and acronyms, and structural formulas, as well as Chemical Abstracts Service registry numbers. Integr Environ Assess Manag 2011;7:513–541. © 2011 SETAC
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            Sources, fate and transport of perfluorocarboxylates.

            This review describes the sources, fate, and transport of perfluorocarboxylates (PFCAs) in the environment, with a specific focus on perfluorooctanoate (PFO). The global historical industry-wide emissions of total PFCAs from direct (manufacture, use, consumer products) and indirect (PFCA impurities and/or precursors) sources were estimated to be 3200-7300 tonnes. It was estimated that the majority (approximately 80%) of PFCAs have been released to the environment from fluoropolymer manufacture and use. Although indirect sources were estimated to be much less importantthan direct sources, there were larger uncertainties associated with the calculations for indirect sources. The physical-chemical properties of PFO (negligible vapor pressure, high solubility in water, and moderate sorption to solids) suggested that PFO would accumulate in surface waters. Estimated mass inventories of PFO in various environmental compartments confirmed that surface waters, especially oceans, contain the majority of PFO. The only environmental sinks for PFO were identified to be sediment burial and transport to the deep oceans, implying a long environmental residence time. Transport pathways for PFCAs in the environment were reviewed, and it was concluded that, in addition to atmospheric transport/degradation of precursors, atmospheric and ocean water transport of the PFCAs themselves could significantly contribute to their long-range transport. It was estimated that 2-12 tonnes/ year of PFO are transported to the Artic by oceanic transport, which is greater than the amount estimated to result from atmospheric transport/degradation of precursors.
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              Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction.

              Animal models are commonly used in the preclinical development of new drugs to predict the metabolic behaviour of new compounds in humans. It is, however, important to realise that humans differ from animals with regards to isoform composition, expression and catalytic activities of drug-metabolising enzymes. In this review the authors describe similarities and differences in this respect among the different species, including man. This may be helpful for drug researchers to choose the most relevant animal species in which the metabolism of a compound can be studied for extrapolating the results to humans. The authors focus on CYPs, which are the main enzymes involved in numerous oxidative reactions and often play a critical role in the metabolism and pharmacokinetics of xenobiotics. In addition, induction and inhibition of CYPs are compared among species. The authors conclude that CYP2E1 shows no large differences between species, and extrapolation between species appears to hold quite well. In contrast, the species-specific isoforms of CYP1A, -2C, -2D and -3A show appreciable interspecies differences in terms of catalytic activity and some caution should be applied when extrapolating metabolism data from animal models to humans.
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                Author and article information

                Journal
                Critical Reviews in Toxicology
                Critical Reviews in Toxicology
                Informa UK Limited
                1040-8444
                1547-6898
                May 05 2014
                May 2014
                May 05 2014
                May 2014
                : 44
                : sup1
                : 1-81
                Article
                10.3109/10408444.2014.905767
                24793953
                b9636cac-5a1b-4cb7-bd6c-f2a41af54240
                © 2014
                History

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