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Editor's Highlight: Comparative Dose-Response Analysis of Liver and Kidney Transcriptomic Effects of Trichloroethylene and Tetrachloroethylene in B6C3F1 Mouse. | LitMetric

AI Article Synopsis

  • TCE and PCE are common environmental pollutants that pose risks to health, yet there's inadequate comparative data on their effects, prompting this study to investigate their impacts on liver and kidney in mice.
  • The study administered varying doses of TCE and PCE to male mice and assessed the resulting liver and kidney effects, finding that PCE had more significant effects and higher levels of a key metabolite, trichloroacetic acid (TCA).
  • The research highlights the importance of transcriptomic data for understanding toxicity mechanisms in humans and suggests that these effects occur at doses comparable to established health risk levels for these chemicals.

Article Abstract

Trichloroethylene (TCE) and tetrachloroethylene (PCE) are ubiquitous environmental contaminants and occupational health hazards. Recent health assessments of these agents identified several critical data gaps, including lack of comparative analysis of their effects. This study examined liver and kidney effects of TCE and PCE in a dose-response study design. Equimolar doses of TCE (24, 80, 240, and 800 mg/kg) or PCE (30, 100, 300, and 1000 mg/kg) were administered by gavage in aqueous vehicle to male B6C3F1/J mice. Tissues were collected 24 h after exposure. Trichloroacetic acid (TCA), a major oxidative metabolite of both compounds, was measured and RNA sequencing was performed. PCE had a stronger effect on liver and kidney transcriptomes, as well as greater concentrations of TCA. Most dose-responsive pathways were common among chemicals/tissues, with the strongest effect on peroxisomal β-oxidation. Effects on liver and kidney mitochondria-related pathways were notably unique to PCE. We performed dose-response modeling of the transcriptomic data and compared the resulting points of departure (PODs) to those for apical endpoints derived from long-term studies with these chemicals in rats, mice, and humans, converting to human equivalent doses using tissue-specific dosimetry models. Tissue-specific acute transcriptional effects of TCE and PCE occurred at human equivalent doses comparable to those for apical effects. These data are relevant for human health assessments of TCE and PCE as they provide data for dose-response analysis of the toxicity mechanisms. Additionally, they provide further evidence that transcriptomic data can be useful surrogates for in vivo PODs, especially when toxicokinetic differences are taken into account.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837274PMC
http://dx.doi.org/10.1093/toxsci/kfx165DOI Listing

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