Toxicity assessments of selected trichloroethylene and perchloroethylene metabolites in three in vitro human placental models

• Published in: Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2022-04, Vol.109, p.109-120
• Main Authors: Elkin, Elana R., Su, Anthony L., Kilburn, Brian A., Bakulski, Kelly M., Armant, D. Randall, Loch-Caruso, Rita
• Format: Article
• Language: English
• Subjects: Cysteine - metabolism; Dichloroacetate (DCA); Female; HTR-8/SVneo; Humans; Perchloroethylene (PERC); Placenta - metabolism; Pregnancy; S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC); S-(1,2-dichlorovinyl)-L-cysteine (DCVC); Solvents; Tetrachloroethylene; Tetrachloroethylene - metabolism; Tetrachloroethylene - toxicity; Trichloroacetate (TCA); Trichloroethylene (TCE); Trichloroethylene - toxicity
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2022.03.003

Residential and occupational exposures to the industrial solvents perchloroethylene (PERC) and trichloroethylene (TCE) present public health concerns. In humans, maternal PERC and TCE exposures can be associated with adverse birth outcomes. Because PERC and TCE are biotransformed to toxic metabolites and placental dysfunction can contribute to adverse birth outcomes, the present study compared the toxicity of key PERC and TCE metabolites in three in vitro human placenta models. We measured cell viability and caspase 3 + 7 activity in the HTR-8/SVneo and BeWo cell lines, and caspase 3 + 7 activity in first trimester villous explant cultures. Cultures were exposed for 24 h to 5–100 µM S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), or 5–200 µM trichloroacetate (TCA) and dichloroacetate (DCA). DCVC significantly reduced cell viability and increased caspase 3 + 7 activity in HTR-8/SVneo cells at a lower concentration (20 µM) compared with concentrations toxic to BeWo cells and villous explants. Similarly, TCVC reduced cell viability and increased caspase 3 + 7 activity in HTR-8/SVneo cells but not in BeWo cells. TCA and DCA had only negligible effects on HTR-8/SVneo or BeWo cells. This study advances understanding of potential risks of PERC and TCE exposure during pregnancy by identifying metabolites toxic in placental cells and tissues. [Display omitted] •DCVC (20 µM) reduced viability and elevated caspase 3 + 7 activity in HTR-8/SVneo cells.•DCVC (50 µM) reduced viability and elevated caspase 3 + 7 activity in BeWo cells.•DCVC (50 µM) elevated caspase 3 + 7 activity in placental villous explants.•TCVC (50 µM) reduced viability and elevated caspase 3 + 7 activity in HTR-8/SVneo cells.•TCA and DCA had only negligible effects on HTR-8/SVneo and BeWo cells.