Abstract A05: Cumulative risk, key characteristics of carcinogens, and hallmarks of cancer analysis for carcinogenic drinking water contaminants

Classic toxicologic and carcinogenic evaluations involve exposure to a single agent, an approach that misses the health impacts of co-occurring exposures to carcinogenic chemicals. To understand the molecular processes that underpin cancer development in people and the carcinogenic impact of environmental pollutants, it is critical to assess the potential health impacts of co-occurring contaminants that are found in common media such as air, water, food products, and consumer products. If environmentally relevant mixtures of chemicals are causing or substantially contributing to cancer, the public health consequences would be profound. A cumulative cancer risk assessment can help in the development of approaches to minimize the burden of cancer due to carcinogenic contaminants in the environment. Here we present an analysis for drinking water in which we identify common combinations of co-occurring carcinogenic contaminants in drinking water. We utilize a risk-based cancer metric as well as a mode of action analysis based on the Hallmarks of Cancer and Key Characteristics of Carcinogens frameworks. Applying this method to drinking water contaminant occurrence data between 2010 and 2017 for the United States reveals that 269,957,711 people served by 43,142 community water systems may be exposed to a mixture of carcinogenic contaminants at levels above the de minimis risk. Based on an assessment of 22 carcinogenic water contaminants, we estimated that 98,657 lifetime cancer cases could be due to contaminated tap water. Almost half of the estimated cancer cases are due to arsenic, while the rest of the risk is due to the presence of disinfection byproducts, radiologic contaminants, and hexavalent chromium. The risk is unevenly distributed across community water systems with approximately 1/3 of the expected cancer cases found in systems serving 10,000-100,000 people and another 1/3 of expected cases in systems serving 100,000-1 million people. In contrast, water systems serving communities smaller than 10,000 people, while contributing less than a fifth of attributable cancer cases, often represent highest individual risks in terms of contaminant exposure for residents served by those systems. A temporal analysis of accumulated cancer risk indicates that for some exposure scenarios, reaching and exceeding the one-in-one-million risk level can occur early in life during sensitive windows of development. In conclusion, real-life exposure information can be helpful for probing the pathways leading to environmental carcinogenesis and also for integrating information from multiple risk assessment frameworks. Citation Format: Sydney S. Evans, Alexis Temkin, Chris Campbell, Olga V. Naidenko. Cumulative risk, key characteristics of carcinogens, and hallmarks of cancer analysis for carcinogenic drinking water contaminants [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A05.