Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum

Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor α (PPARα). However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear. The aim of the present study was to determine the metabolite profiles in serum and urine upon exposure of mice to TCE, to aid in determining the metabolic response to TCE exposure and the contribution of DCA and TCA to TCE toxicity. C57BL/6 mice were administered TCE, TCA, or DCA, and urine and serum subjected to ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based global metabolomics analysis. The ions were identified through searching metabolomics databases and by comparison with authentic standards, and quantitated using multiple reactions monitoring. Quantitative polymerase chain reaction of mRNA, biochemical analysis, and liver histology were also performed. TCE exposure resulted in a decrease in urine of metabolites involved in fatty acid metabolism, resulting from altered expression of PPARα target genes. TCE treatment also induced altered phospholipid homeostasis in serum, as revealed by increased serum lysophosphatidylcholine 18:0 and 18:1, and phosphatidylcholine metabolites. TCA administration revealed similar metabolite profiles in urine and serum upon TCE exposure, which correlated with a more robust induction of PPARα target gene expression associated with TCA than DCA treatment. These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum.

Transport of volatile chlorinated hydrocarbons in unsaturated aggregated media

Transport of volatile hydrocarbons in soils is largely controlled by interactions of vapours with the liquid and solid phase. Sorption on solids of gaseous or dissolved comPounds may be important. Since the contact time between a chemical and a specific sorption site can be rather short, kinetic or mass-transfer resistance effects may be relevant. An existing mathematical model describing advection and diffusion in the gas phase and diffusional transport from the gaseous phase into an intra-aggregate water phase is modified to include linear kinetic sorption on ps-solid and water-solid interfaces. The model accounts for kinetic mass transfer between all three phases in a soil. The solution of the Laplace-transformed equations is inverted numerically. We performed transient column experiments with 1,1,2-Trichloroethane, Trichloroethylene, and Tetrachloroethylene using air-dry solid and water-saturated porous glass beads. The breakthrough curves were calculated based on independently estimated parameters. The model calculations agree well with experimental data. The different transport behaviour of the three compounds in our system primarily depends on Henry's constants.