Academic journal article Environmental Health Perspectives

Research Recommendations for Selected IARC-Classified Agents

Academic journal article Environmental Health Perspectives

Research Recommendations for Selected IARC-Classified Agents

Article excerpt

OBJECTIVES: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans.

DATA SOURCES: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent.

DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches.

DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation.

CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

KEY WORDS: animal, carcinogen, carcinogenesis, epidemiology, human, IARC, mechanisms of carcinogenicity, occupational. Environ Health Perspect 118:1355--1362 (2010). doi:10.1289/ehp.0901828 [Online 18 June 2010]

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Forty-five years after the World Health Organization recognized cancer as a world health problem by creating the International Agency for Research on Cancer (IARC), carcinogenic exposures in the workplace remain a concern. Many known and suspected carcinogens are found in today's workplaces, and uncertainties about the health effects of exposure to these hazards have delayed regulatory action and the search for safer alternatives. In this review we focus primarily on chemicals, metals, dusts, and physical agents for which there is widespread human exposure, predominantly in occupational settings, and we address unresolved questions regarding carcinogenicity. Most of these agents are in IARC Groups 2A and 2B--agents for which there is sufficient evidence of carcinogenicity in animals but limited evidence for carcinogenicity in humans.

A project to systematically identify data gaps was initiated by the National Occupational Research Agenda team of the U.S. National Institute for Occupational Safety and Health (NIOSH) to enhance occupational cancer research and involved joint planning with IARC, the American Cancer Society, the U.S. National Institute of Environmental Health Sciences, and the U.S. National Cancer Institute. In this review we present the results of this effort and identify opportunities for further research that would resolve classification uncertainties for selected high-priority agents. The process included a meeting to identify high-priority agents; expert reviews of each agent to update the literature since the last Monograph evaluation and to identify research priorities; and a workshop to discuss the identified data gaps and approaches. Expert reviewers were selected by the planning committee based on expertise in epidemiology and toxicology and on knowledge of the agents. For many agents, we recognized that opportunities for cohort studies would be limited, and reviewers were encouraged to consider possible experimental studies to elucidate carcinogenic mechanisms and molecular epidemiologic studies to develop intermediate biomarker data that could be used in classification. …

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