Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
MetadataShow full item record
This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by-nc/4.0/
© The Author 2015. 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.
Showing items related by title, author, creator and subject.
Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: Systematic review and network meta-analysisVeettil, S.; Jinatongthai, P.; Nathisuwan, S.; Teerawattanapong, N.; Ching, S.; Lim, K.; Saokaew, S.; Phisalprapa, P.; Reid, Christopher; Chaiyakunapruk, N. (2018)Background: Various interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) ...
Beatty, Shelley Ellen (2003)The long-term regular use of tobacco and hazardous alcohol use are responsible for significant mortality and morbidity as well as social and economic harm in Australia each year. There is necessary the more cost-efficient ...
Si, Si; Boyle, T.; Heyworth, J.; Glass, D.; Saunders, C.; Fritschi, Lin (2015)© 2015 Springer Science+Business Media New York To investigate the association between different types of physical activity (PA) and breast cancer. A case–control study of breast cancer was conducted in Western Australia ...