Metabolism of trichloroethylene following inhalation exposure in mice
This study found that DCA, TCA, and TCEOH-gluc are the most prevalent metabolites of TCE in mice, highlighting the need for further investigation into their neurotoxic effects.
Where it sits
this study against the rest of the glutathione (gsh) corpusSummary and findings
This study measured the metabolism of trichloroethylene (TCE) in mice following inhalation exposure. Mice were exposed to 100 ppm TCE for 4 hours, and various metabolites were identified in plasma, brain, and liver samples. The findings indicate that DCA, TCA, and TCEOH-gluc are the most prevalent TCE metabolites in this model.
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
Background
This paper addresses the metabolism of trichloroethylene (TCE), an environmental pollutant linked to increased risk of Parkinson's disease (PD). Previous studies have shown that 40 - 75% of absorbed TCE is metabolized, but knowledge of the neurotoxicity of its metabolites is limited. Understanding TCE metabolism in animal models can provide insights into potential human health risks.
Methods
The study involved an inhalation exposure design with mice exposed to 100 ppm TCE for 4 hours. Biological samples, including plasma, brain, and liver, were collected up to 24 hours post-exposure. The primary outcome measure was the identification of TCE metabolites using high-resolution mass spectrometry.
Results
The primary endpoint identified DCA, TCA, and TCEOH-gluc as the most prevalent metabolites in TCE-exposed mice. Specific numeric findings regarding metabolite concentrations were not reported in the abstract. The study utilized both targeted and untargeted mass spectrometry to analyze samples.
Interpretation
The findings indicate that DCA, TCA, and TCEOH-gluc are significant metabolites of TCE in mice, which may have implications for understanding TCE toxicity. However, the clinical significance of these findings is uncertain due to the study's reliance on animal models. The absence of human data and the potential for species-specific metabolic differences limit the applicability of these results to human health.
Key findings
- Mice were exposed to 100 ppm TCE for 4 hours.
- DCA, TCA, and TCEOH-gluc were identified as the most prevalent TCE metabolites.
- Plasma, brain, and liver samples were collected up to 24 hours after exposure.
- High-resolution mass spectrometry (HRMS) was used to identify metabolites.
Limitations
- Limited to mouse models, no human data.
- Short exposure duration of 4 hours.
- No specific numeric findings reported for metabolite concentrations.
- Potential species-specific metabolic differences.