A new approach to the classification of carcinogenicity

Abstract

Concern over substances that may cause cancer has led to various classification schemes to recognize carcinogenic threats and provide a basis to manage those threats. The least useful schemes have a binary choice that declares a substance carcinogenic or not. This overly simplistic approach ignores the complexity of cancer causation by considering neither how the substance causes cancer, nor the potency of that mode of action. Consequently, substances are classified simply as “carcinogenic”, compromising the opportunity to properly manage these kinds of substances. It will likely be very difficult, if not impossible, to incorporate New Approach Methodologies (NAMs) into binary schemes. In this paper we propose a new approach cancer classification scheme that segregates substances by both mode of action and potency into three categories and, as a consequence, provides useful guidance in the regulation and management of substances with carcinogenic potential. Examples are given, including aflatoxin (category A), trichlorethylene (category B), and titanium dioxide (category C), which demonstrate the clear differentiation among these substances that generate appropriate levels of concern and management options.

Carcinogenic Chemicals in Occupational Settings: A Tool for Comparison and Translation between Different Classification Systems

“…Concerning the different classification systems, as reported in multiple studies [5,[5][6][7][8][9], debates exist on both the crucial role of the classification systems and the importance of creating a new classification system which considers all the available scientific data.…”

“…The review article of Felter and colleagues [7] summarizes themes and discussions resulting from an expert workshop on the scientific limitations of the current binary carcinogenicity classification scheme and the tiered testing strategies founded on new approach methodologies. This concept is reiterated by the article of Doe and colleagues [8,9], where a new-approach cancer classification scheme has been proposed. As highlighted by this discussion, there is not a unique and homogeneous classification approach to assess and classify the carcinogenicity of chemicals.…”

Genotoxicity assessment: opportunities, challenges and perspectives for quantitative evaluations of dose–response data

“…Over several decades, the presence or absence of molecular effect thresholds for genotoxicity but also for the more complex endpoint of carcinogenicity has been subject to lively debate (Neumann 2009 ). In this context, the integration of detailed information on the genotoxic and/or carcinogenic MoA is increasingly regarded as an opportunity to refine regulatory assessment and classification schemes (Bolt 2008 ; Doe et al 2022 ; ECHA/RAC and SCOEL 2017 ; Felter et al 2021 ; Hartwig et al 2020 ). However, within the rather practical remit of regulatory toxicology and public health protection, the question is not only if there is a mechanistically plausible threshold for a particular genotoxic substance but also whether this threshold can be determined precisely enough to allow reliable conclusions to be drawn about the presence or absence of health concerns.…”

Towards a future regulatory framework for chemicals in the European Union – Chemicals 2.0

“…The proposed classification scheme is similar to a recently proposed approach to the classification of carcinogenicity ( Doe et al, 2022 ). In this respect, the three-level classification system, in which TK and TD considerations are considered independently, partially addresses several critiques of the current binary classification system ( Boobis et al, 2016 ; Cohen et al, 2019 ; Doe et al, 2019 ).…”