Multicriteria approach to select polyaromatic river mutagen candidates

Area of Science:

• Environmental Chemistry
• Analytical Chemistry
• Toxicology

Background:

• Identifying specific toxicants in complex environmental mixtures is crucial for understanding observed toxic effects.
• Effect-directed analysis (EDA) is a key approach, but often hindered by the challenge of unknown compound identification.

Purpose of the Study:

• To develop and validate a workflow for the identification of unknown compounds in environmental mixtures using nontarget liquid chromatography-high resolution mass spectrometry (LC-HRMS).
• To link specific chemical structures to toxic effects, particularly mutagenicity, within complex environmental samples.

Main Methods:

• Utilized molecular formulas from previous studies as a starting point for compound identification.
• Performed database searches (ChemSpider) to retrieve candidate compounds for each molecular formula.
• Applied a multi-stage selection process including HRMS/MS fragmentation, ionization efficiency, physical-chemical properties (pKa, logP), predicted retention times, and toxicological data (mutagenicity).
• Employed nontarget LC-HRMS for comprehensive analysis of environmental fractions.

Main Results:

• Successfully reduced the number of potential candidates for unknown compounds significantly.
• Tentatively identified possible mutagens within a mutagenic environmental fraction.
• Positively identified benzyl(diphenyl) phosphine oxide as a nonmutagen in the analyzed fraction.
• Encountered limitations in the positive identification of mutagens due to the unavailability of commercial standards.

Conclusions:

• The developed workflow is an innovative and promising approach for identifying unknown toxicants in environmental mixtures.
• The method effectively narrows down candidate compounds and aids in linking chemical structures to toxicological endpoints.
• Further advancements are possible, particularly in addressing the availability of analytical standards for definitive identification of causative agents.