Recent Developments in the IARC Monographs Progamme Kate Z. Guyton for the IARC Monographs Programme
(IMO Group / ESC Section - International Agency for Research on Cancer)
A Two-Step Evaluation Process Cancer in humans
• Sufficient evidence • Limited evidence • Inadequate evidence
Cancer in Experimental animals
• Sufficient evidence • Limited evidence • Inadequate evidence
Mechanistic and Other Relevant Data
• “Weak,” “moderate,” or “strong”?
• Operative in humans?
Step 1: Categorize each line of evidence
using defined terms
Step 2: Integrate findings in overall
evaluations
Overall evaluation
Group 1 Carcinogenic to humans (120) Group 2A Probably carcinogenic to humans (81) Group 2B Possibly carcinogenic to humans (299) Group 3 Not classifiable as to its carcinogenicity to humans (502) Group 4 Probably not carcinogenic to humans (1)
New Developments in Evidence Synthesis and Evaluation in IARC Monographs
Evaluations by Independent Scientists
• Cancer hazard identification is the first step in cancer prevention
• IARC evaluations support public health actions to reduce exposures to carcinogens, for example: o WHO Air Quality Guidelines (Volume 109, Group 1
evaluation of outdoor air pollution) o Stockholm Convention listing of Persistent Organic
Pollutants: PCBs, lindane, pentachlorophenol (Group 1); DDT, aldrin/dieldrin (Group 2A); perfluorooctane sulfonic acid (Group 2B)
From Evaluations to Action
Challenges: • How to search systematically for data on cancer epidemiology, cancer bioassays
and relevant mechanisms, including from high- throughput data streams? • How to bring uniformity in data extraction within and across Working Groups? • How to evaluate the voluminous mechanistic database efficiently? Solutions: • Implement on-line tools to standardize evidence search, extraction, analysis • Pioneer systematic approach to mechanistic evidence evaluation based on key
characteristics of carcinogens (Smith et al., 2016) • Pilot incorporation of high-throughput data relevant to cancer mechanisms
Overview of Evaluation Process From Recommendations to Evaluations
IARC Secretariat
Coordinates all aspects of the
evaluation
Working Group Independent scientists
without conflict of interest
Review science and develop evaluations
Invited Specialists Scientists with relevant
knowledge but a competing interest
Representatives of governments and health
agencies
Observers Scientists with a
competing interest: observe but do not influence outcomes
Attend meetings but do not write cancer reviews or
contribute to evaluations
Group 1
Group 3
Group 3 4 consistently and
strongly supported by a broad range of mechanistic and other relevant data
Group 4
2A belongs to a mechanistic class
2B with supporting evidence from mechanistic and other relevant data
Group 3
2A belongs to a mechanistic class
2B with strong evidence from mechanistic and other relevant data
Group 3
Sufficient Limited Inadequate ESLC EVIDENCE IN EXPERIMENTAL ANIMALS
2A belongs to a mechanistic class where other members are classified in Groups 1 or 2A
Group 2B (exceptionally, Group 2A)
ESLC
Limited
Sufficient
Inadequate
1 strong evidence in exposed humans
Group 2A
1 strong evidence in exposed humans
2A strong evidence … mechanism also operates in humans
Group 2B 3 strong evidence …
mechanism does not operate in humans
EVIDENCE IN HUMANS
Integrating Epidemiology, Animal Bioassay and Mechanistic Evidence
Occupational exposures
Complex Mixtures
Chemicals Lifestyle Factors
Biological and Physical
Agents
Objectively identify relevant evidence with targeted literature searches
Organize results to facilitate evidence review and synthesis
Integrate high-throughput data, organised by key characteristic
Standardise data extraction, analysis
Recent highlights: • Volume 109, outdoor air pollution evaluated in Group 1 • Volume 111, fluoro-edenite evaluated in Group 1 • Volume 112, 113, and 117, new or updated evaluations of
pesticides in Group 1 (pentachlorophenol, lindane), 2A (glyphosate, DDT) or 2B (parathion)
• Volume 118, welding evaluated in Group 1 • Volume 119, various chemicals that cause tumours of the
urinary tract in rodents evaluated in Group 2B • Volume 120, re-evaluation of benzene in Group 1
References •Guha N, Guyton KZ, et al. Prioritizing Chemicals for Risk Assessment Using Chemoinformatics: Examples from the IARC Monographs on Pesticides. Environ Health Perspect. 2016 124(12):1823-1829. •Smith MT, Guyton KZ, et al. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis. Environ Health Perspect. 2016 124(6):713-21 •Straif K, Loomis D, et al. Future priorities for the IARC Monographs. Lancet Oncol. 2014;15:683–684.
ACKNOWLEDGEMENTS Staff of the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans
Lamia Benbrahim-Tallaa
Véronique Bouvard
Sandrine Égraz
Elisabeth Elbers
Fatiha El Ghissassi
Yann Grosse
Neela Guha
Helene Lorenzen-Augros
Kurt Straif
Heidi Mattock
Fiona Gould
Kate Guyton
Financial support for the Monographs was received from: o National Cancer Institute, USA (Cooperative
Agreement U01 CA33193) o US NIEHS/National Toxicology Program
o European Commission (DG for Employment, Social Affairs, and Inclusion; and EaSI (http://ec.europa.eu/social/easi)
Solene Quennehen
monographs. iarc.fr
Marieke Dusenberg
Dana Loomis