RT Journal Article SR Electronic T1 Integrating exposure knowledge and serum suspect screening as a new approach to biomonitoring: An application in firefighters and office workers JF bioRxiv FD Cold Spring Harbor Laboratory SP 630848 DO 10.1101/630848 A1 Grashow, Rachel A1 Bessonneau, Vincent A1 Gerona, Roy R. A1 Wang, Aolin A1 Trowbridge, Jessica A1 Lin, Thomas A1 Buren, Heather A1 Rudel, Ruthann A. A1 Morello-Frosch, Rachel YR 2019 UL http://biorxiv.org/content/early/2019/05/10/630848.abstract AB Background Women firefighters are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so may not detect important, lesser known, exposures.Objectives The Women Firefighters Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap.Methods Using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) we sought to identify candidate chemicals of interest in serum samples from 83 women firefighters (FF) and 79 office workers (OW) in San Francisco. Through the GSS approach we identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 740 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected chemicals for confirmation based on a priori criteria: 1) detection frequency or peak area differences between OW and FF; 2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and 3) not currently measured in large biomonitoring studies.Results We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame retardant metabolites, phenols, pesticides, nitro-and nitroso-compounds, and per- and polyfluoroalkyl substances. The average number of chemicals from the database that were detected in participants was 72 and 70 in FF and OW, respectively. We confirmed 8 of the 20 prioritized suspect chemicals –including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate--by running a matrix spike of the reference standards and using m/z, retention time and the confirmation of at least two fragment ions as criteria for matching.Conclusion GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies.