Year: 2026
Type: preprint
Abstract: Trichloroethylene (TCE) is a pervasive environmental pollutant associated with elevated risk of developing Parkinson’s disease (PD). Studies characterizing TCE metabolism in humans indicate that 40–75% of the absorbed dose is metabolized, suggesting that TCE toxicity may be attributable to its metabolites. However, there is limited knowledge of TCE metabolite neurotoxicity. We conducted a TCE inhalation study in mice followed by high-resolution mass spectrometry (HRMS) on brain, liver, and blood to identify which TCE metabolites were present following human-relevant TCE exposure. Mice were exposed to 100 ppm TCE for 4 hours. Plasma, brain, and liver were collected from each animal up to 24 hours after exposure. We developed a method capable of detecting TCE metabolites trichloroacetic acid (TCA), dichloroacetic acid (DCA), monochloroacetic acid (MCA), trichloroethanol (TCEOH), trichloroethanol glucuronide (TCEOH-gluc), S-(1,2-dichlorovinyl)glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), N -acetyl- S -(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), and untargeted metabolites using a single extraction protocol on a liquid chromatography-based mass spectrometry system (LC-MS/MS). Targeted analysis of TCE-exposed biological samples identified DCA, TCA, and TCEOH-gluc. Untargeted analysis of TCE-exposed mouse brain revealed previously established and novel pathway perturbations associated with TCE exposure. Together, these findings indicate that DCA, TCA, and TCEOH-gluc are the most prevalent TCE metabolites in mice. The novel pathways perturbed by TCE exposure warrant further exploration to better understand the mechanisms underlying the toxicity of TCE and its metabolites.
Language: English
Subfield: Toxicology
Domain: Life Sciences
Open Access status: green
Awards: Mega-scale Identification tools for xenobiotic metabolism, UAB Training Program in Neurodegeneration, Vesicular modulation of dopamine neuron toxicity, Advanced training in environmental health and data science: molecules to populations, The role of lysosomal impairment in trichloroethylene induced Parkinsonian neurodegeneration
OpenAlex ID: W7222926978