Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Creators: name: Wade, Mark
name: Gonzalez, Michael J.
name: Brooks, Samira A.
name: Gonzalez, Laetitia
name: Sabbisetti, Venkata
name: Weisz, Judith
name: Felsher, Dean W.
name: Odero-Marah, Valerie
name: Sone, Hideko
name: Goldberg, Gary S.
name: Ivana Scovassi, A.
name: Hsu, Hsue Yin
name: Wolf, Gregory T.
name: Kim Lyerly, H.
name: Eltom, Sakina
name: Hamid, Roslida Abd
name: Prudhomme, Kalan R.
name: Chiaradonna, Ferdinando
name: Calaf, Gloria M.
name: Al-Temaimi, Rabeah
name: Miousse, Isabelle R.
name: Krishnan, Harini
name: Kravchenko, Julia
name: Engström, Wilhelm
name: Ogunkua, Olugbemiga
name: Van Larebeke, Nik
name: Rojas, Emilio
name: Collins, Andrew R.
name: Ryan, Elizabeth P.
name: Bay, Sarah N.
name: Martinez-Leal, Juan Fernando
name: Darroudi, Firouz
name: Vento, Renza
name: Nangia-Makker, Pratima
name: Charles, Amelia K.
name: Lowe, Leroy
name: Van Schooten, Frederik J.
name: Goodson, William H.
name: Eriksson, Staffan
name: Woodrick, Jordan
name: Sun, Jun
name: Ghosh, Paramita M.
name: Carlin, Danielle J.
name: Ochieng, Josiah
name: Hamid, Hasiah Ab
name: Rojanasakul, Yon
name: Manjili, Masoud H.
name: Vadgama, Pankaj
name: Lee, Tae Jin
name: Carnero, Amancio
name: Martin, Francis L.
name: Castellino, Robert C.
name: Carpenter, David O.
name: Valverde, Mahara
name: Christopher, Joseph A.
name: Kimryn Rathmell, W.
name: Ryeom, Sandra
name: Cruickshanks, Nichola
name: Koch, Daniel C.
name: Ponce-Cusi, Richard
name: Heneberg, Petr
name: Brown, Dustin G.
name: Dormoy, Valérian
name: Gilbertson, Michael
name: Langie, Sabine A.S.
name: Koturbash, Igor
name: Otsuki, Takemi
name: Naus, Christian C.
name: Mehta, Rekha
name: Chen, Zhenbang
name: Ostrosky-Wegman, Patricia
name: Massfelder, Thierry
name: Zhou, Binhua P.
name: McCawley, Lisa J.
name: Harris, Shelley A.
name: Casey, Stephanie C.
name: Xia, Menghang
name: Romano, Maria Fiammetta
name: Whitfield, Jonathan R.
name: Laird, Dale W.
name: Li, Lin
name: Dong, Chenfang
name: Brooks Robey, R.
name: Pavanello, Sofia
name: Ratovitski, Edward
name: Roman, Jesse
name: Lleonart, Matilde
name: Vondráček, Jan
name: Narayanan, Kannan Badri
name: Marignani, Paola A.
name: Brunborg, Gunnar
name: Laconi, Ezio
name: Wise, John Pierce
name: Nangami, Gladys
name: Marongiu, Fabio
name: Vaccari, Monica
name: Berg, Arthur
name: Jian, Le
name: Curran, Colleen S.
name: Moon, Eun Yi
name: Wise, Sandra S.
name: de Cerain Salsamendi, Adela Lopez
name: Yasaei, Hemad
name: Forte, Stefano
name: Krishnakumar, P. K.
name: Thompson, Patricia
name: Zhang, Luoping
name: Raju, Jayadev
name: Lasfar, Ahmed
name: Palorini, Roberta
name: Mondello, Chiara
name: Romano, Simona
name: Memeo, Lorenzo
name: Andrade-Vieira, Rafaela
name: Salem, Hosni K.
name: Karamouzis, Michalis V.
name: Dent, Paul
name: Blanco-Aparicio, Carmen
name: Baglole, Carolyn J.
name: Kondoh, Hiroshi
name: Wagemaker, Gerard
name: Decker, William K.
name: Cheng, Qiang Shawn
name: Di Fiore, Riccardo
name: Hultman, Tove
name: Ali, Abdul Manaf
name: Kleinstreuer, Nicole
name: Luanpitpong, Sudjit
name: Gulliver, Linda
name: Salzberg, Anna C.
name: D'Abronzo, Leandro S.
name: Chapellier, Marion
name: Yedjou, Clement
name: Kirsch-Volders, Micheline
name: Guarnieri, Tiziana
name: Nahta, Rita
name: Ward, Andrew
name: Leyns, Luc
name: Cohen-Solal, Karine A.
name: Hsu, Chia Wen
name: Lin, Liang Tzung
name: Chen, Tao
name: Corsini, Emanuela
name: Maguer-Satta, Veronique
name: Papagerakis, Silvana
name: Williams, Marc A.
name: Roy, Rabindra
name: Williams, Graeme
name: Sinha, Ranjeet K.
name: Roy, Debasish
name: Klaunig, James E.
name: Singh, Neetu
name: Kuemmerle, Nancy B.
name: Park, Hyun Ho
name: Barclay, Barry J.
name: Bisson, William H.
name: Vermeulen, Louis
name: Soucek, Laura
name: Khatami, Mahin
name: Sanderson, Thomas
name: Koppen, Gudrun
name: Darbre, Philippa
name: Ahmed, Nuzhat
name: Amedei, Amedeo
name: Dornetshuber-Fleiss, Rita
name: Al-Mulla, Fahd
name: Olsen, Ann Karin
name: Luqmani, Yunus
name: Hu, Zhiwei
name: Azqueta, Amaya
name: Leung, Po Sing
name: Moorwood, Kim
name: Colacci, Annamaria
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: 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.