Study Title:

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment:

Study Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the
World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers
attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to
mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed
11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical
disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark
effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/
mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas
59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis
suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety
of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic
research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued
before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization
International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses
that are not fully aligned with our current understanding of cancer biology.

Study Information


Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
Carcinogenesis.
2015 January

Full Study

http://carcin.oxfordjournals.org/content/36/Suppl_1/S254.full.pdf+html