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    Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

    235339_235339.pdf (1.793Mb)
    Access Status
    Open access
    Authors
    Goodson, W.
    Lowe, L.
    Carpenter, D.
    Gilbertson, M.
    Ali, A.
    de Cerain Salsamendi, A.
    Lasfar, A.
    Carnero, A.
    Azqueta, A.
    Amedei, A.
    Charles, A.
    Collins, A.
    Ward, A.
    Salzberg, A.
    Colacci, A.
    Olsen, A.
    Berg, A.
    Barclay, B.
    Zhou, B.
    Blanco-Aparicio, C.
    Baglole, C.
    Dong, C.
    Mondello, C.
    Hsu, C.
    Naus, C.
    Yedjou, C.
    Curran, C.
    Laird, D.
    Koch, D.
    Carlin, D.
    Felsher, D.
    Roy, D.
    Brown, D.
    Ratovitski, E.
    Ryan, E.
    Corsini, E.
    Rojas, E.
    Moon, E.
    Laconi, E.
    Marongiu, F.
    Al-Mulla, F.
    Chiaradonna, F.
    Darroudi, F.
    Martin, F.
    Van Schooten, F.
    Goldberg, G.
    Wagemaker, G.
    Nangami, G.
    Calaf, G.
    Williams, G.
    Wolf, G.
    Koppen, G.
    Brunborg, G.
    Kim Lyerly, H.
    Krishnan, H.
    Hamid, H.
    Yasaei, H.
    Sone, H.
    Kondoh, H.
    Salem, H.
    Hsu, H.
    Park, H.
    Koturbash, I.
    Miousse, I.
    Ivana Scovassi, A.
    Klaunig, J.
    Vondrácek, J.
    Raju, J.
    Roman, J.
    Wise, J.
    Whitfield, J.
    Woodrick, J.
    Christopher, J.
    Ochieng, J.
    Martinez-Leal, J.
    Weisz, J.
    Kravchenko, J.
    Sun, J.
    Prudhomme, K.
    Narayanan, K.
    Cohen-Solal, K.
    Moorwood, K.
    Gonzalez, L.
    Soucek, L.
    Jian, Le
    D'Abronzo, L.
    Lin, L.
    Li, L.
    Gulliver, L.
    McCawley, L.
    Memeo, L.
    Vermeulen, L.
    Leyns, L.
    Zhang, L.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Goodson, W. and Lowe, L. and Carpenter, D. and Gilbertson, M. and Ali, A. and de Cerain Salsamendi, A. and Lasfar, A. et al. 2015. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead. Carcinogenesis. 36 (s1): pp. S254-S296.
    Source Title
    Carcinogenesis
    DOI
    10.1093/carcin/bgv039
    ISSN
    0143-3334
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by-nc/4.0/

    URI
    http://hdl.handle.net/20.500.11937/24418
    Collection
    • Curtin Research Publications
    Abstract

    © The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

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