Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers

Firefighters (FF) are exposed to recognized and probable carcinogens,
yet there are few studies of chemical exposures and associated health
concerns in women FFs, such as breast cancer. Biomonitoring often
requires a priori selection of compounds to be measured, and so, it
may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring
Collaborative (WFBC) created a biological sample archive and conducted
a general suspect screen (GSS) to address this data gap. Using liquid
chromatography–quadrupole time-of-flight tandem mass spectrometry,
we sought to identify candidate chemicals of interest in serum samples
from 83 women FFs and 79 women office workers (OW) in San Francisco.
We identified chemical peaks by matching accurate mass from serum
samples against a custom chemical database of 722 slightly polar phenolic
and acidic compounds, including many of relevance to firefighting
or breast cancer etiology. We then selected tentatively identified
chemicals for confirmation based on the following 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. 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. Of the 20 suspect chemicals selected for validation, 8
were confirmed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. GSS provides a powerful high-throughput approach to
identify and prioritize novel chemicals for biomonitoring and health
studies.