Breast cancer rates vary across California, with some areas having significantly higher rates than others (Roberts et al., 2013). Many factors can contribute to this variability; differential exposure to environmental contaminants, e.g., via drinking water supplies, is one possible causative factor.

Carcinogens may be added to household water supplies in four main ways. They can be: (i) present in the source water prior to any human inputs, (ii) contributed by regional or local land uses such as transportation, energy production or agriculture, (iii) added (or removed) by water system treatment design and operation choices such as disinfection (which can form byproducts), membrane filtration (which can remove many substances) or leaching from materials used in the community water distribution system, or (iv) contributed by household-level factors like distance from the treatment plant (which impacts concentrations of disinfection byproducts) or household plumbing materials, It is important to the breast cancer community to understand the identities and the sources of any unregulated chemicals present in drinking water that may contribute to differential rates of the disease across California.

Californians are continuously exposed to a wide variety of structurally diverse chemicals from many sources, including environmental and food contaminants, therapeutic agents, chemicals from commercial and consumer products, personal care products and many other sources.

Known mammary gland carcinogens come from a broad array of chemical classes (e.g., dioxins, polychlorinated biphenyls (PCBs), phenols like bisphenol A (BPA), phthalates, polyfluorinated alkyl substances (PFAS), halogenated flame retardants and solvents, pesticides, drinking water disinfectant by-products, pharmaceuticals, hormones, natural products, and dyes); many representatives of these broad chemical classes are not routinely monitored in water supplies. Compounds in many of these chemical classes have also been identified as endocrine disruptors, which can produce a diverse spectrum of adverse health effects including enhancing the development and progression of breast cancer (Beszterda and Franski, 2018; Davis et al., 1993; McLachlan, 2016; Rutkowska et al., 2016; Trevino 2015).

Since most breast cancers are estrogen-dependent, increased growth and proliferation of breast cancer can be stimulated by chemicals that can directly activate and/or enhance the activity of estrogen receptors (ERs) (Lecomte et al., 2017; Rutkowska et al., 2016; Trevino et al., 2015). Many estrogenic endocrine disrupting chemicals (EDCs) have been identified in recent years, and it has been suggested that the increased incidence of breast cancer in industrialized countries is linked to such chemicals (Bergman et al., 2013; Davis et al., 1993; Gao et al., 2015; Lecomte 2017; McLachlan, 2016; Rutkowska et al., 2016; Safe, 1998; Trevino 2016). Given the well- documented and widespread presence of estrogenic chemicals in surface waters and their potential to end up in drinking water (Beszterda and Franski, 2018; Kuch and Ballschmitter, 2001; Rahman et al., 2009), the detection, identification and characterization of estrogenic chemicals is of major importance.

Advances in the accuracy and resolution of mass spectrometry have spurred rapid developments in “nontarget analysis” in which a much broader array of potentially estrogenic chemicals can be monitored compared with traditional, targeted approaches. These developments have allowed the detection of previously unsuspected industrial chemicals (Ruff et al., 2015) and chemical transformation products (Kern et al., 2009) in the Rhine River, novel PFAS in the Tennessee River (Newton et al., 2017), and environmental transformation products in the San Francisco Bay Delta (Moschet et al., 2017). Application of these techniques to drinking water has led to discovery of novel disinfection byproducts (Richardson et al., 2008) and other potentially toxic organic compounds (Sultan and Gabryelski, 2006). Systematic application of these novel techniques to California drinking water supplies has the potential to fill important knowledge gaps regarding environmental contributors to breast cancer development.

Conducting such a systematic assessment of the presence of compounds that might contribute to breast cancer in California’s drinking water supplies is complicated by the complex array and mixture of water sources used across the state, combined with the diversity in type and stringency of the treatment processes employed. Superimposed on this patchwork of sources and treatment processes are variations in land uses that may degrade the quality of groundwater and surface water including: agriculture, transportation, fire-fighting, energy extraction, wastewater discharge, and industry; inputs to water supplies from these activities can vary both seasonally and regionally.

The research proposed here will select households following a stratified sampling scheme to maximize statewide representativeness of water sources, will analyze wintertime and summertime tap water samples from each household using four nontarget chemical analysis methods accompanied by measurement of estrogenic activity of the extracts and identified chemicals, and will assess whether the detected compounds are known mammary gland carcinogens and/or will seek to identify any compounds associated with elevated endocrine disrupting activity.

Our study design allows us to determine whether household level, treatment system level, watershed level, or source type (groundwater or surface water) factors play the largest role in contributing known mammary gland carcinogens, nontarget chemicals, and estrogenic activity to household water supplies, informing subsequent management and research activities. Collectively, the research will answer the questions:

  1. Which water sources are associated with the highest levels of endocrine disrupting compounds or known mammary gland carcinogens? Are these water sources in communities with historically elevated breast cancer rates compared with areas with lower rates? Are particular nontarget compounds associated with particular source water types? How do these compounds vary with space and time within a particular water system?
  2. How do water treatment processes, particularly disinfection processes and advanced treatment operations influence the levels and identities of estrogen active or carcinogenic compounds?