International Workshop (July 2013)

Historically, the World Health Organization (WHO)/International Programme on Chemical Safety (IPCS) has been tasked with the development of the scientific basis for the sound management of chemicals to strengthen national capabilities and capacities for chemical safety. This group has done a considerable amount of work on aggregate/cumulative risk assessment (i.e., combined exposures to multiple chemicals) and they have emphasized that chemicals that act by the same “mode of action” often act in a potency-corrected “dose additive” manner (noting that the term “mode of action” has been defined as “a biologically plausible sequence of key events leading to an observed effect supported by robust experimental observations and mechanistic data”).

This basic principle is recognized at the national level in some countries. For example, in the United States, the EPA's guidance document on cumulative risk (2002) notes that a “common mechanism of toxicity” pertains to “two or more pesticide chemicals or other substances that cause a common toxic effect(s) by the same, or essentially the same, sequence of major biochemical events (i.e., interpreted as mode of action)”. And the US EPA's guidance on Carcinogenic Risk Assessment (2005) defines mode of action as “a sequence of key events and processes, starting with interaction of an agent with a cell, proceeding through operational and anatomical changes, and resulting in cancer formation” (where a “key event” is defined as an empirically observable precursor step that is itself a necessary element of the mode of action or is a biologically based marker for such an element), noting that examples of modes of (carcinogenic) action are such things as mutagenicity, mitogenesis, inhibition of cell death, cytotoxicity with reparative cell proliferation, and immune suppression.

However, the existence of this policy has not yet translated into cumulative risk assessment practices that routinely make use these of common modes of (carcinogenic) action. Moreover, the science of cancer is advancing rapidly and the most complete, most frequently cited framework for cancer is the “hallmarks of cancer” framework. This is framework encompasses all of these modes of (carcinogenic) action and should serve well as a model for risk assessment purposes but its utility has not yet been recognized or fully exploited. Therefore “Getting to Know Cancer” will instigate an international workshop on this topic that is tentatively scheduled to take place in July of 2013.

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International Workshop (July 2013)

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