New view of cancer development focuses on subtle, combined effects
Rethinking Carcinogens: Conclusion and Recommendations
It is clear that reducing or eliminating exposures to carcinogenic chemicals in the environment could prevent a large number of cancers. However, the hallmarks of cancer framework suggests that complete carcinogens may only be one piece of the total cancer risk. Development of cancer is a multistep, multi-hit process that occurs through the accumulation of cancer hallmarks in a cell. The understanding of this model of cancer development is applied in the Halifax Project’s new ideas about how combinations of chemicals can cause cancer. It identified 85 chemicals common in the environment that can disrupt one or more cancer-related hallmark process. Combinations of such chemicals could very well have synergistic carcinogenic effects, which we are only beginning to discover. Focusing exclusively on complete carcinogens fails to consider the possibility that combinations of chemicals could work in concert to lay the groundwork for cancer and knock out the body’s defenses against it.
Just as troubling are the Halifax Project’s findings that low doses of a large number of partial carcinogens can affect cancer-related pathways. This calls into question whether current safety standards, which are generally based on high-dose toxicity testing, are sufficiently protective.
When you consider the vast number of possible chemical combinations, many of which act at low doses, the relationship between exposures and cancer gets even more complex. Although this makes the study and regulation of chemical mixtures an extremely daunting task, the findings of the Halifax Project suggest that the hallmarks of cancer framework can provide a blueprint for setting priorities based on the mixtures’ carcinogenic potential. Continuing to identify and regulate only complete carcinogens ignores the serious threat that chemical mixtures can pose to public health.
Recommendations for research and health:
- The hallmarks of cancer should be used to set priorities for screening chemicals and chemical mixtures for carcinogenic effects.
- Further study is necessary to determine the effects of chronic lifetime exposure to chemical mixtures, including the accumulation of chemicals in the body, with particular attention to chemicals that disrupt cancer-related hallmark processes.
- Chemical safety standards should be revisited so as to carefully consider low-dose health effects.
Recommendations for policy, with special consideration for reform of the Toxic Substances Control Act (TSCA):
- Federal and state regulation should extend beyond “complete carcinogens” and take into account the effects of chemical mixtures on specific modes of cancer causation – the hallmarks of cancer.
- Reform of TSCA should not hinder EPA from adopting new risk assessment models based on the Halifax Project’s insight that combinations of hallmark-disrupting chemicals can have synergistic carcinogenic effects, as this information becomes available.
- TSCA should include provisions for EPA to consider cumulative exposures to single chemicals and chemical combinations.
- Chemicals that disrupt hallmark processes should be given special consideration, since these chemicals are unlikely to be regulated under EPA’s current risk assessment and cost/benefit analyses.
- Reform of TSCA should include a special section providing research funding and an evaluation process for the health effects of chemical combinations.