Advanced Characterization of Environmental Pollutant Metabolism in Human Skin

Area of Science:

• Environmental Health
• Toxicology
• Analytical Chemistry

Background:

• Ultrafine particles (UFPs) containing polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are environmental pollutants linked to health concerns.
• The skin is a primary target for environmental contaminants, necessitating research into pollutant metabolism.
• Existing in vitro models often lack metabolic activity, and animal testing faces ethical limitations.

Purpose of the Study:

• To investigate the metabolic fate of benzo[a]pyrene (BaP) in a human skin model.
• To develop and validate a novel analytical approach for characterizing BaP metabolism.
• To identify BaP metabolites formed in the skin.

Main Methods:

• Utilized a 3D reconstructed human epidermis (RHE) model for physiological relevance.
• Employed stable isotope labeling (SIL) with deuterium-labeled BaP (BaP-d12) for precise quantification.
• Applied liquid chromatography-high-resolution mass spectrometry (LC-HRMS) coupled with stable isotope filtering for metabolite identification.

Main Results:

• Identified five distinct BaP phase I metabolites within the RHE model.
• Detected mono-hydroxylated, dihydroxylated, and quinone derivatives of BaP.
• Demonstrated the efficacy of SIL-LC-HRMS for comprehensive metabolic profiling.

Conclusions:

• Coupling stable isotope labeling with LC-HRMS provides a powerful tool for characterizing BaP metabolic pathways in human skin.
• The identified metabolites enhance understanding of BaP detoxification and potential adverse effects.
• This analytical strategy is promising for studying the metabolism of other environmental pollutants in skin.