Lauren E Koval1,2, Kathie L Dionisio3, Katie Paul Friedman4, Kristin K Isaacs4, Julia E Rager5,6,7. 1. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 2. The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 3. Immediate Office of the Assistant Administrator, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA. 4. Center for Computational Toxicology and Exposure, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC, USA. 5. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jrager@unc.edu. 6. The Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jrager@unc.edu. 7. Curriculum in Toxicology and Environmental Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA. jrager@unc.edu.
Abstract
BACKGROUND: Although evidence linking environmental chemicals to breast cancer is growing, mixtures-based exposure evaluations are lacking. OBJECTIVE: This study aimed to identify environmental chemicals in use inventories that co-occur and share properties with chemicals that have association with breast cancer, highlighting exposure combinations that may alter disease risk. METHODS: The occurrence of chemicals within chemical use categories was characterized using the Chemical and Products Database. Co-exposure patterns were evaluated for chemicals that have an association with breast cancer (BC), no known association (NBC), and understudied chemicals (UC) identified through query of the Silent Spring Institute's Mammary Carcinogens Review Database and the U.S. Environmental Protection Agency's Toxicity Reference Database. UCs were ranked based on structure and physicochemical similarities and co-occurrence patterns with BCs within environmentally relevant exposure sources. RESULTS: A total of 6793 chemicals had data available for exposure source occurrence analyses. 50 top-ranking UCs spanning five clusters of co-occurring chemicals were prioritized, based on shared properties with co-occuring BCs, including chemicals used in food production and consumer/personal care products, as well as potential endocrine system modulators. SIGNIFICANCE: Results highlight important co-exposure conditions that are likely prevalent within our everyday environments that warrant further evaluation for possible breast cancer risk. IMPACT STATEMENT: Most environmental studies on breast cancer have focused on evaluating relationships between individual, well-known chemicals and breast cancer risk. This study set out to expand this research field by identifying understudied chemicals and mixtures that may occur in everyday environments due to their patterns of commercial use. Analyses focused on those that co-occur alongside chemicals associated with breast cancer, based upon in silico chemical database querying and analysis. Particularly in instances when understudied chemicals share physicochemical properties and structural features with carcinogens, these chemical mixtures represent conditions that should be studied in future clinical, epidemiological, and toxicological studies.
BACKGROUND: Although evidence linking environmental chemicals to breast cancer is growing, mixtures-based exposure evaluations are lacking. OBJECTIVE: This study aimed to identify environmental chemicals in use inventories that co-occur and share properties with chemicals that have association with breast cancer, highlighting exposure combinations that may alter disease risk. METHODS: The occurrence of chemicals within chemical use categories was characterized using the Chemical and Products Database. Co-exposure patterns were evaluated for chemicals that have an association with breast cancer (BC), no known association (NBC), and understudied chemicals (UC) identified through query of the Silent Spring Institute's Mammary Carcinogens Review Database and the U.S. Environmental Protection Agency's Toxicity Reference Database. UCs were ranked based on structure and physicochemical similarities and co-occurrence patterns with BCs within environmentally relevant exposure sources. RESULTS: A total of 6793 chemicals had data available for exposure source occurrence analyses. 50 top-ranking UCs spanning five clusters of co-occurring chemicals were prioritized, based on shared properties with co-occuring BCs, including chemicals used in food production and consumer/personal care products, as well as potential endocrine system modulators. SIGNIFICANCE: Results highlight important co-exposure conditions that are likely prevalent within our everyday environments that warrant further evaluation for possible breast cancer risk. IMPACT STATEMENT: Most environmental studies on breast cancer have focused on evaluating relationships between individual, well-known chemicals and breast cancer risk. This study set out to expand this research field by identifying understudied chemicals and mixtures that may occur in everyday environments due to their patterns of commercial use. Analyses focused on those that co-occur alongside chemicals associated with breast cancer, based upon in silico chemical database querying and analysis. Particularly in instances when understudied chemicals share physicochemical properties and structural features with carcinogens, these chemical mixtures represent conditions that should be studied in future clinical, epidemiological, and toxicological studies.
Authors: Kristin K Isaacs; Kathie Dionisio; Katherine Phillips; Charles Bevington; Peter Egeghy; Paul S Price Journal: J Expo Sci Environ Epidemiol Date: 2019-11-11 Impact factor: 5.563
Authors: Antony J Williams; Christopher M Grulke; Jeff Edwards; Andrew D McEachran; Kamel Mansouri; Nancy C Baker; Grace Patlewicz; Imran Shah; John F Wambaugh; Richard S Judson; Ann M Richard Journal: J Cheminform Date: 2017-11-28 Impact factor: 5.514
Authors: Kathie L Dionisio; Katherine Phillips; Paul S Price; Christopher M Grulke; Antony Williams; Derya Biryol; Tao Hong; Kristin K Isaacs Journal: Sci Data Date: 2018-07-10 Impact factor: 6.444
Authors: Kathie L Dionisio; Alicia M Frame; Michael-Rock Goldsmith; John F Wambaugh; Alan Liddell; Tommy Cathey; Doris Smith; James Vail; Alexi S Ernstoff; Peter Fantke; Olivier Jolliet; Richard S Judson Journal: Toxicol Rep Date: 2015-01-02