IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards

David M DeMarini; William Gwinn; Emily Watkins; Brad Reisfeld; Weihsueh A Chiu; Lauren Zeise; Dinesh Barupal; Parveen Bhatti; Kevin Cross; Eugenia Dogliotti; Jason M Fritz; Dori Germolec; Maria Helena Guerra Andersen; Kathryn Z Guyton; Jennifer Jinot; David H Phillips; Roger R Reddel; Nathaniel Rothman; Martin van den Berg; Roel C H Vermeulen; Paolo Vineis; Amy Wang; Maurice Whelan; Akram Ghantous; Michael Korenjak; Jiri Zavadil; Zdenko Herceg; Sandra Perdomo; Laure Dossus; Shirisha Chittiboyina; Danila Cuomo; John Kaldor; Elisa Pasqual; Gabrielle Rigutto; Roland Wedekind; Caterina Facchin; Fatiha El Ghissassi; Aline de Conti; Mary K Schubauer-Berigan; Federica Madia

doi:10.1289/ehp15389

IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards

David M DeMarini, William Gwinn, Emily Watkins, Brad Reisfeld, Weihsueh A Chiu, Lauren Zeise, Dinesh Barupal, Parveen Bhatti, Kevin Cross, Eugenia Dogliotti, Jason M Fritz, Dori Germolec, Maria Helena Guerra Andersen, Kathryn Z Guyton, Jennifer Jinot, David H Phillips, Roger R Reddel, Nathaniel Rothman, Martin van den Berg, Roel C H VermeulenPaolo Vineis, Amy Wang, Maurice Whelan, Akram Ghantous, Michael Korenjak, Jiri Zavadil, Zdenko Herceg, Sandra Perdomo, Laure Dossus, Shirisha Chittiboyina, Danila Cuomo, John Kaldor, Elisa Pasqual, Gabrielle Rigutto, Roland Wedekind, Caterina Facchin, Fatiha El Ghissassi, Aline de Conti, Mary K Schubauer-Berigan, Federica Madia

School of Life and Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

BackgroundThe 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The International Agency for Research on Cancer (IARC) Monographs programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.ObjectivesWe sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations.MethodsA group of experts from different disciplines reviewed the IARC Monographs experience with the KCs of carcinogens, discussing three main themes: a) the interpretation of end points forming the evidence base for the KCs, b) the incorporation of data from novel assays on the KCs, and c) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.DiscussionConsensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the IARC Monographs or in other contexts. https://doi.org/10.1289/EHP15389.

Original language	English
Pages (from-to)	25001
Number of pages	1
Journal	Environmental health perspectives
Volume	133
Issue number	2
DOIs	https://doi.org/10.1289/ehp15389
Publication status	Published - 1 Feb 2025

Keywords

Humans
Neoplasms
Carcinogens
Risk Assessment
Environmental Exposure

Access to Document

10.1289/ehp15389

Cite this

DeMarini, D. M., Gwinn, W., Watkins, E., Reisfeld, B., Chiu, W. A., Zeise, L., Barupal, D., Bhatti, P., Cross, K., Dogliotti, E., Fritz, J. M., Germolec, D., Andersen, M. H. G., Guyton, K. Z., Jinot, J., Phillips, D. H., Reddel, R. R., Rothman, N., van den Berg, M., ... Madia, F. (2025). IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards. Environmental health perspectives, 133(2), 25001. https://doi.org/10.1289/ehp15389

@article{0a1a141fb6fb489f809e12f661ba0556,

title = "IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards",

abstract = "BackgroundThe 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The International Agency for Research on Cancer (IARC) Monographs programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.ObjectivesWe sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations.MethodsA group of experts from different disciplines reviewed the IARC Monographs experience with the KCs of carcinogens, discussing three main themes: a) the interpretation of end points forming the evidence base for the KCs, b) the incorporation of data from novel assays on the KCs, and c) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.DiscussionConsensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the IARC Monographs or in other contexts. https://doi.org/10.1289/EHP15389.",

keywords = "Humans, Neoplasms, Carcinogens, Risk Assessment, Environmental Exposure",

author = "DeMarini, {David M} and William Gwinn and Emily Watkins and Brad Reisfeld and Chiu, {Weihsueh A} and Lauren Zeise and Dinesh Barupal and Parveen Bhatti and Kevin Cross and Eugenia Dogliotti and Fritz, {Jason M} and Dori Germolec and Andersen, {Maria Helena Guerra} and Guyton, {Kathryn Z} and Jennifer Jinot and Phillips, {David H} and Reddel, {Roger R} and Nathaniel Rothman and {van den Berg}, Martin and Vermeulen, {Roel C H} and Paolo Vineis and Amy Wang and Maurice Whelan and Akram Ghantous and Michael Korenjak and Jiri Zavadil and Zdenko Herceg and Sandra Perdomo and Laure Dossus and Shirisha Chittiboyina and Danila Cuomo and John Kaldor and Elisa Pasqual and Gabrielle Rigutto and Roland Wedekind and Caterina Facchin and {El Ghissassi}, Fatiha and {de Conti}, Aline and Schubauer-Berigan, {Mary K} and Federica Madia",

year = "2025",

month = feb,

day = "1",

doi = "10.1289/ehp15389",

language = "English",

volume = "133",

pages = "25001",

journal = "Environmental health perspectives",

issn = "0091-6765",

publisher = "National Institute of Environmental Health Sciences (NIEHS)",

number = "2",

}

DeMarini, DM, Gwinn, W, Watkins, E, Reisfeld, B, Chiu, WA, Zeise, L, Barupal, D, Bhatti, P, Cross, K, Dogliotti, E, Fritz, JM, Germolec, D, Andersen, MHG, Guyton, KZ, Jinot, J, Phillips, DH, Reddel, RR, Rothman, N, van den Berg, M, Vermeulen, RCH, Vineis, P, Wang, A, Whelan, M, Ghantous, A, Korenjak, M, Zavadil, J, Herceg, Z, Perdomo, S, Dossus, L, Chittiboyina, S, Cuomo, D, Kaldor, J, Pasqual, E, Rigutto, G, Wedekind, R, Facchin, C, El Ghissassi, F, de Conti, A, Schubauer-Berigan, MK & Madia, F 2025, 'IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards', Environmental health perspectives, vol. 133, no. 2, pp. 25001. https://doi.org/10.1289/ehp15389

TY - JOUR

T1 - IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards

AU - DeMarini, David M

AU - Gwinn, William

AU - Watkins, Emily

AU - Reisfeld, Brad

AU - Chiu, Weihsueh A

AU - Zeise, Lauren

AU - Barupal, Dinesh

AU - Bhatti, Parveen

AU - Cross, Kevin

AU - Dogliotti, Eugenia

AU - Fritz, Jason M

AU - Germolec, Dori

AU - Andersen, Maria Helena Guerra

AU - Guyton, Kathryn Z

AU - Jinot, Jennifer

AU - Phillips, David H

AU - Reddel, Roger R

AU - Rothman, Nathaniel

AU - van den Berg, Martin

AU - Vermeulen, Roel C H

AU - Vineis, Paolo

AU - Wang, Amy

AU - Whelan, Maurice

AU - Ghantous, Akram

AU - Korenjak, Michael

AU - Zavadil, Jiri

AU - Herceg, Zdenko

AU - Perdomo, Sandra

AU - Dossus, Laure

AU - Chittiboyina, Shirisha

AU - Cuomo, Danila

AU - Kaldor, John

AU - Pasqual, Elisa

AU - Rigutto, Gabrielle

AU - Wedekind, Roland

AU - Facchin, Caterina

AU - El Ghissassi, Fatiha

AU - de Conti, Aline

AU - Schubauer-Berigan, Mary K

AU - Madia, Federica

PY - 2025/2/1

Y1 - 2025/2/1

N2 - BackgroundThe 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The International Agency for Research on Cancer (IARC) Monographs programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.ObjectivesWe sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations.MethodsA group of experts from different disciplines reviewed the IARC Monographs experience with the KCs of carcinogens, discussing three main themes: a) the interpretation of end points forming the evidence base for the KCs, b) the incorporation of data from novel assays on the KCs, and c) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.DiscussionConsensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the IARC Monographs or in other contexts. https://doi.org/10.1289/EHP15389.

AB - BackgroundThe 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The International Agency for Research on Cancer (IARC) Monographs programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures. The use of this framework has significantly enhanced the identification and organization of relevant mechanistic data, minimized bias in evaluations, and enriched the knowledge base regarding the mechanisms of known and suspected carcinogens.ObjectivesWe sought to report the main outcomes of an IARC Scientific Workshop convened by the IARC to establish appropriate, transparent, and uniform application of the KCs in future IARC Monographs evaluations.MethodsA group of experts from different disciplines reviewed the IARC Monographs experience with the KCs of carcinogens, discussing three main themes: a) the interpretation of end points forming the evidence base for the KCs, b) the incorporation of data from novel assays on the KCs, and c) the integration of the mechanistic evidence as part of cancer hazard identification. The workshop participants assessed the relevance and the informativeness of multiple KCs-associated end points for the evaluation of mechanistic evidence in studies of exposed humans and experimental systems.DiscussionConsensus was reached on how to enhance the use of in silico, molecular, and cellular high-output and high-throughput data. In addition, approaches to integrate evidence across the KCs and opportunities to improve methodologies of mechanistic evaluation of cancer hazards were explored. The findings described herein and in a forthcoming IARC technical report will support future working groups of experts in reporting and interpreting results under the KCs framework within the IARC Monographs or in other contexts. https://doi.org/10.1289/EHP15389.

KW - Humans

KW - Neoplasms

KW - Carcinogens

KW - Risk Assessment

KW - Environmental Exposure

U2 - 10.1289/ehp15389

DO - 10.1289/ehp15389

M3 - Article

SN - 0091-6765

VL - 133

SP - 25001

JO - Environmental health perspectives

JF - Environmental health perspectives

IS - 2

ER -