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