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

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.

Building collaborative partnerships for climate change action in Maputo, Mozambique

The authors examine partnerships as a policy strategy for climate change governance in cities in the Global South. Partnerships offer the opportunity to link the actions of diverse actors operating at different scales and, thus, they may be flexible enough to deal with uncertain futures and changing development demands. However, simultaneously, partnerships may lack effectiveness in delivering action at the local level, and may constitute a strategy for some actors to legitimate their objectives in spite of the interests of other partners. Engaging with the specific example of urban governance in Maputo, Mozambique, the authors present an analysis of potential partnerships in this context, in relation to the actors that are willing and able to intervene to deliver climate change action. What, they ask, are the challenges to achieving common objectives in partnerships from the perspective of local residents in informal settlements? The analysis describes a changing context of climate change governance in the city, in which the prospects of access to international finance for climate change adaptation are moving institutional actors towards engaging with participatory processes at the local level. However, the analysis suggests a question about the extent to which local communities are actually perceived as actors with legitimate interests who can intervene in partnerships, and whether their interests are recognised.