Current criteria to establish human carcinogens.

Area of Science:

• Toxicology
• Carcinogenesis
• Risk Assessment

Background:

• Global health agencies identify carcinogens to reduce cancer burden.
• Current programs often use mechanistic data to support epidemiological or animal study findings.
• Recent guidelines, like the EPA's, expand on assessing mechanistic data.

Purpose of the Study:

• To propose an alternative paradigm for carcinogen identification.
• To shift the role of mechanistic studies from supporting to central in carcinogen identification.
• To align carcinogen identification with a multi-factorial view of carcinogenesis.

Main Methods:

• Review of existing national and international carcinogen identification programs.
• Analysis of the role of mechanistic data in current evaluation frameworks.
• Proposal of a new paradigm focusing on identifying key human cancer precursor events and testing agents' effects on them.

Main Results:

• Current programs primarily use mechanistic data to support or discount other study findings.
• The proposed paradigm identifies carcinogens by understanding their role in cancer development processes.
• This mechanistic-first approach may allow earlier identification of carcinogens.

Conclusions:

• Mechanistic studies can play a central role in identifying carcinogens.
• An agent's role in cancer development processes, not just tumor induction, defines it as a carcinogen.
• This paradigm offers a potentially faster route to carcinogen identification, independent of long-term bioassays or epidemiological data.