Nontargeted Discovery of Novel Contaminants in the Great Lakes Region: A Comparison of Fish Fillets and Fish Consumers

Abstract

Sport fish fillets and human sera (fish consumers) were collected in the Lake Superior and Lake Michigan basin and screened for novel contaminants using the isotopic profile deconvoluted chromatogram (IPDC) algorithm. The IPDC algorithm was extended beyond traditional Cl/Br filters to detect additional potential bioaccumulative and toxic (PBT) such as perfluoroalkyl substances (PFAS). The IPDC algorithm screened for approximately 13.5 million theoretical molecular formulas. Additional algorithm modules were developed to detect data independent MS/MS fragmentation products and a retention time index calculator using a series of 13 C-labeled perfluoroalkyl carboxylic acids ( 13 C-PFCAs). Ten potential compound classes were isolated including six untargeted PFAS, six homologue groups of polyfluorinated carboxylic acids, polyfluorinated telomer alcohols (PoFTOHs), two hydroxylated polychlorobiphenyls, pesticides, herbicides, antifungals, pharmaceuticals, artificial sweeteners, and personal care products with minimal postprocessing efforts. The algorithm isolated 48 ubiquitous PoFTOHs in both fish fillet and serum of fish consumers suggesting a region wide distribution of this class of compounds. The 3, 4, and 7 fluorine substituted PoFTOH were the most abundant congeners in both biological matrices.

IDSL.UFA assigns high confidence molecular formula annotations for untargeted LC/HRMS datasets in metabolomics and exposomics

“…IDSL.UFA can only confirm isotopic profiles match (Figure S.11); however, a confirmatory fragment ([M-C3F6O] -) was observed for the chemistry of C12 in MS1 which was consistent with the published MS/MS fragmentation (Figure S.12). 40 Levels of Cl-PFTrEAs were similar to the commonly known legacy halogenated compounds 14 for human serum samples (Figure 6).…”

“…To flag the potential peaks related to chemical exposures in the pregnancy study (ST001430), we first assigned a molecular formula using an ECS that may cover diverse halogenated compounds that were not found in the IDSL. 37 Authentic standards for Cl-PFTrEAs are not readily available; therefore a confidence level 3b (isotopic profile match combined with fragmentation-based candidate) is suggested for these annotations according to a recently proposed PFAS identification confidence level by Charbonnet et al 38 Levels of Cl-PFTrEAs were similar to the commonly known legacy halogenated compounds 14 for human serum samples (Figure 4). These findings also show that IDSL.UFA software can potentially detect chemicals of public health concerns in a human biospecimen and can be helpful in expanding the existing database of exposome chemicals.…”

“…Many other successful tools have been developed to detect Br/Cl containing compounds which had a characteristics isotopic profile in the MS1 data. [11][12][13][14][15]19 MFAssignR 20 can assign molecular formula using MS1 data using Kendrick mass defect combined with isotopic signatures of selected elements. But these tools were not designed and tested for large-scale human biospecimens studies which is routinely seen in the exposome research.…”

“…11 Isotopic profiles are distinguishable mass spectral signature that represent atomic masses and their natural abundances in the molecular formulas of a compound. 12 Despite the known limitations of high-resolution mass spectrometry instruments, observed experimental isotopic profiles for an ionized compound may sufficiently match the theoretical counterpart within instrument errors in many instances 11,13 , allowing to annotate LC/HRMS peaks with molecular formula 14 . Peak annotation by isotopic profile matching should be performed using efficient computational strategies to account for instrumental errors, multi-sample studies, biological plausibility and chemical diversity.…”

Widening the Lens on PFASs: Direct Human Exposure to Perfluoroalkyl Acid Precursors (pre-PFAAs)

“…Progress in this area will greatly improve understanding of the importance of human exposure to pre-PFAAs and will contribute to closing the mass balance on organofluorine in human blood. Total organic fluorine measurements indicate the likely presence of unknown PFASs in human blood from the general population, , but only a handful of novel PFASs have been identified in human serum. ,− The presence of unidentified pre-PFAAs, including intermediate transformation products, has been raised as a potential contributor to the unknown PFAS fraction in serum from the general population …”