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Goodson III, William H. and Lowe, Leroy and Carpenter, David O. and Gilbertson, Michael and Ali, Abdul Manaf and Salsamendi, Adela Lopez de Cerain and Lasfar, Ahmed and Carnero, Amancio and Azqueta, Amaya and Amedei, Amedeo and Charles, Amelia K. and Collins, Andrew R. and Ward, Andrew and Salzberg, Anna C. and Colacci, Anna Maria and Olsen, Ann Karin and Berg, Arthur and Barclay, Barry J. and Zhou, Binhua P. and Aparicio, Carmen Blanco and Baglole, Carolyn J. and Dong, Chenfang and Mondello, Chiara and Chia, Wen Hsu and Naus, Christian C. and Yedjou, Clement and Curran, Colleen S. and Laird, Dale W. and Koch, Daniel C. and Carlin, Danielle J. and Felsher, Dean W. and Roy, Debasish and Brown, Dustin G. and Ratovitski, Edward and Ryan, Elizabeth P. and Corsini, Emanuela and Rojas, Emilio and Eun, Yi Moon and Laconi, Ezio and Marongiu, Fabio and Al-Mulla, Fahd and Chiaradonna, Ferdinando and Darroudi, Firouz and Martin, Francis L. and Schooten, Frederik J. Van and Goldberg, Gary S. and Wagemaker, Gerard and Nangami, Gladys N. and Calaf, Gloria M. and Williams, Graeme P. and Wolf, Gregory T. and Koppen, Gudrun and Brunborg, Gunnar and Lyerly, H. Kim and Krishnan, Harini and Ab. Hamid, Hasiah and Yasaei, Hemad and Sone, Hideko and Kondoh, Hiroshi and Salem, Hosni K. and Hsue, Yin Hsu and Hyun, Ho Park and Koturbash, Igor and Miousse, Isabelle R. and Scovassi, A. Ivana and Klaunig, James E. and Vondrá ček, Jan and Raju, Jayadev and Roman, Jesse and Wise Sr., John Pierce and Whitfield, Jonathan R. and Woodrick, Jordan and Christopher, Joseph A. and Ochieng, Josiah and Martinez-Leal, Juan Fernando and Weisz, Judith and Kravchenko, Julia and Sun, Jun and Prudhomme, Kalan R. and Narayanan, Kannan Badri and Cohen-Solal, Karine A. and Moorwood, Kim and Gonzalez, Laetitia and Soucek, Laura and Jian, Le and D’Abronzo, Leandro S. and Liang, Tzung Lin and Li, Lin and Gulliver, Linda and McCawley, Lisa J. and Memeo, Lorenzo and Vermeulen, Louis and Leyns, Luc and Zhang, Luoping and Valverde, Mahara and Khatami, Mahin and Romano, Maria Fiammetta and Chapellier, Marion and Williams, Marc A. and Wade, Mark and Manjili, Masoud H. and Lleonart, Matilde E. and Xia, Menghang and Gonzalez Guzma, Michael J. and Karamouzis, Michalis V. and Kirsch Volders, Micheline and Vaccari, Monica and Kuemmerle, Nancy B. and Singh, Neetu and Cruickshanks, Nichola and Kleinstreuer, Nicole and Larebeke, Nik van and Ahmed, Nuzhat and Ogunkua, Olugbemiga and Krishnakumar, P. K. and Vadgama, Pankaj and Marignani, Paola A. and Ghosh, Paramita M. and Ostrosky Wegman, Patricia and Thompson, Patricia A. and Dent, Paul and Darbre, Philippa and Heneberg, Petr and Po, Sing Leung and Nangia Makker, Pratima and Cheng, Qiang and Robey, R. Brooks and Al-Temaimi, Rabeah and Roy, Rabindra and Andrade Vieira, Rafaela and Sinha, Ranjeet K. and Mehta, Rekha and Vento, Renza and Di Fiore, Riccardo and Ponce Cusi, Richard and Dornetshuber Fleiss, Rita and Nahta, Rita and Castellino, Robert C. and Palorini, Roberta and Abd Hamid @ Abdul Razak, Roslida and Langie, Sabine A. S. and Eltom, Sakina E. and Brooks, Samira A. and Ryeom, Sandra and Wise, Sandra S. and Bay, Sarah N. and Harris, Shelley A. and Papagerakis, Silvana and Romano, Simona and Pavanello, Sofia and Eriksson, Staffan and Forte, Stefano and Casey, Stephanie C. and Luanpitpong, Sudjit and Tae, Jin Lee and Otsuki, Takemi and Chen, Tao and Massfelder, Thierry and Sanderson, Thomas and Guarnieri, Tiziana and Hultman, Tove and Dormoy, Valérian and Odero Mara, Valerie and Sabbisetti, Venkata and Maguer Satta, Veronique and Rathmell, W. Kimryn and Engström, Wilhelm and Decker, William K. and Bisson, William H. and Rojanasakul, Yon and Luqmani, Yunus and Chen, Zhenbang and Hu, Zhiwei
(2015)
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Carcinogenesis, 36 (supp.1).
S254-S296.
ISSN 0143-3334; ESSN: 1460-2180
Abstract
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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