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

© 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...

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Main 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.
Format:	Journal Article
Published:	Oxford University Press 2015
Online Access:	http://hdl.handle.net/20.500.11937/24418

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author	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.
author_facet	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.
author_sort	Goodson, W.
building	Curtin Institutional Repository
collection	Online Access
description	© 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.
first_indexed	2025-11-14T07:52:29Z
format	Journal Article
id	curtin-20.500.11937-24418
institution	Curtin University Malaysia
institution_category	Local University
last_indexed	2025-11-14T07:52:29Z
publishDate	2015
publisher	Oxford University Press
recordtype	eprints
repository_type	Digital Repository
spelling	curtin-20.500.11937-244182017-09-13T15:07:52Z Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead 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. © 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/24418 10.1093/carcin/bgv039 Oxford University Press fulltext
spellingShingle	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. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title	Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title_full	Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title_fullStr	Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title_full_unstemmed	Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title_short	Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
title_sort	assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
url	http://hdl.handle.net/20.500.11937/24418

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

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