Characterization of the Human Exposome and Risk of Reproductive Hormone Disruption by Integrating GC-HRMS Nontarget...

Area of Science:

• Environmental Chemistry
• Toxicology
• Mass Spectrometry

Background:

• The human exposome, encompassing environmental exposures, is incompletely characterized, particularly for nonpolar substances.
• Gas chromatography-high-resolution mass spectrometry (GC-HRMS) is a powerful tool for identifying diverse chemical compounds.
• Nonpolar contaminants and their health impacts, especially endocrine disruption, require further investigation.

Purpose of the Study:

• To screen for and identify nonpolar exogenous contaminants in human blood using non-targeted GC-HRMS analysis.
• To annotate identified molecular features and assess their potential for hormone disruption.
• To investigate the association between chemical exposures and reproductive risk in different residential settings.

Main Methods:

• Non-targeted analysis of whole blood samples (n=155) from healthy Chinese adults using GC-HRMS.
• Molecular networking for annotation of detected molecular features.
• Transfer learning models to predict cumulative hormone-disrupting potential of identified chemicals and perfluoroalkyl substances (PFAS).

Main Results:

• 194 molecular features were annotated, including 93 novel noncyclic alkanes/alkane derivatives, 58 aromatics, 21 halogenated compounds, 16 heterocyclics, and 6 cycloalkanes.
• Perfluoroalkyl substances (PFAS) were associated with follicle-stimulating hormone disruption.
• Aromatic compounds significantly contributed to luteinizing hormone and estradiol disruption, while alkane derivatives showed a 1.7-fold higher reproductive risk in urban/suburban residents compared to rural residents.

Conclusions:

• GC-HRMS is crucial for chemical exposomics, revealing understudied alkane and aromatic derivatives as potential risk factors.
• Alkane derivatives may pose a greater reproductive risk in urban/suburban environments.
• Further research is needed to confirm these findings and elucidate the mechanisms of action.