In an article published on August 12, 2016, in the peer-reviewed journal Environmental Health Perspectives, Mark Miller from the National Institute of Environmental Health Sciences (NIEHS), U.S., and colleagues from the U.S., Canada and United Kingdom summarize the outcomes of the Halifax Project workshop held at the NIEHS in August 2015 (FPF reported). The Halifax Project investigates the contribution of chronic low-dose exposure to mixtures of chemicals not considered human carcinogens to the initiation and progression of cancer (FPF reported), and the proposed Low-Dose Mixture Hypothesis of Carcinogenesis has been discussed in a number of scientific studies and review articles (FPF reported). Here, the scientists report on the main scientific findings and remaining research needs, and discuss novel approaches to research and risk assessment in this area.

The experts concluded that the combined scientific evidence speaks in favor of the novel carcinogenesis hypothesis, warranting further investigation. More understanding needs to be developed of the ways in which the actions of non-carcinogenic mixture constituents combine to affect in vitro and in vivo carcinogenesis processes, which should be characterized both spatially and temporally. Furthermore, the overlap between measurable cancer hallmarks and characteristics of carcinogens should be examined. Future research should integrate the knowledge on epigenetic biomarkers, microbiome, transcriptomics, proteomics, and metabolomics to comprehensively annotate the molecular components of network perturbations, using in silico modeling, high-performance computing and high-resolution imaging approaches.

With regard to risk assessment, it is concluded that the cumulative effects of exposure to chemical mixtures might be underestimated or even missed entirely by the current risk assessment paradigm based on the notion of “single chemical as carcinogen.” Therefore, it is recommended that the regulatory frameworks be restructured to ensure an adequate testing of relevant environmental mixtures. The results of this testing will provide crucial experimental evidence on which future policy decisions should be based.


Miller, M., et al. (2016). “Low-dose mixture hypothesis of carcinogenesis workshop: Scientific underpinnings and research recommendations.Environmental Health Perspectives (published August 12, 2016).