1932

Abstract

The halogenated solvent trichloroethylene (TCE) has had many uses in medicine, construction, consumer products, and the military. Many of these uses have been discontinued or restricted due to its toxicity, which affects multiple target organs and includes both acute, high-dose toxicity and chronic, low-dose toxicity that also encompass several cancers. US and international agencies have conducted risk and hazard assessments for TCE, with comprehensive publications coming out in the last 10–15 years. Accordingly, the focus of this article is to review recently published data since that time (i.e., 2014) that clarify unsettled questions or provide additional insights into the metabolism and mechanisms of toxicity of TCE in several target organs. Besides metabolism, the review focuses on the kidneys, liver, immune system, nervous system, cardiovascular and pulmonary systems, the search for biomarkers, and recent analyses of human cancer risk and incidence from TCE exposure.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-022724-120525
2025-01-23
2025-06-16
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/65/1/annurev-pharmtox-022724-120525.html?itemId=/content/journals/10.1146/annurev-pharmtox-022724-120525&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    The Merck Index Online. 2024.. Trichloroethylene. London:: R. Soc. Chem. https://merckindex.rsc.org/monographs/m11074
    [Google Scholar]
  2. 2.
    EPA (US Environ. Prot. Agency). 2011.. Toxicological review of trichloroethylene (CAS no. 79-01-6): In support of summary information on the integrated risk information system (IRIS). EPA/635/R-09/011F . Washington, DC:: EPA. https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0199tr/0199tr.pdf
    [Google Scholar]
  3. 3.
    IARC (Int. Agency Res. Cancer). 2014.. Trichloroethylene, Tetrachloroethylene and Some Other Chlorinated Agents. Volume 106 . Lyon, France:: IARC
    [Google Scholar]
  4. 4.
    NTP (Natl. Toxicol. Prog.). 2015.. Report on Carcinogens: Monograph on Trichloroethylene. Research Triangle Park, NC:: US Dep. Health Hum. Serv. https://ntp.niehs.nih.gov/sites/default/files/ntp/roc/monographs/finaltce_508.pdf
    [Google Scholar]
  5. 5.
    ATSDR. 2022.. Substance priority list. . Agency for Toxic Substances and Disease Registry. https://www.atsdr.cdc.gov/spl/index.html
    [Google Scholar]
  6. 6.
    EPA (US Environ. Prot. Agency). 2024.. Superfund Chemical Data Matrix (SCDM). US Environ. . Prot. Agency. https://www.epa.gov/superfund/superfund-chemical-data-matrix-scdm
    [Google Scholar]
  7. 7.
    IARC (Int. Agency Res. Cancer). 1995.. Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals. Volume 63. Lyon, France:: IARC
    [Google Scholar]
  8. 8.
    EPA (US Environ. Prot. Agency). 2020.. Risk Evaluation for Trichloroethylene. Washington, DC:: EPA. https://www.epa.gov/sites/default/files/2020-11/documents/1._risk_evaluation_for_trichloroethylene_tce_casrn_79-01-6.pdf
    [Google Scholar]
  9. 9.
    Chiu WA, Jinot J, Scott CS, Makris SL, Cooper GS, et al. 2013.. Human health effects of trichloroethylene: key findings and scientific issues. . Environ. Health Perspect. 121::30311
    [Crossref] [Google Scholar]
  10. 10.
    Lash LH, Chiu WA, Guyton KZ, Rusyn I. 2014.. Trichloroethylene biotransformation and its role in mutagenicity, carcinogenicity and target organ toxicity. . Mutat. Res. Rev. 762::2236
    [Crossref] [Google Scholar]
  11. 11.
    Rusyn I, Chiu WA, Lash LH, Kromhout H, Hansen J, Guyton KZ. 2014.. Trichloroethylene: mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard. . Pharmacol. Ther. 141::5568
    [Crossref] [Google Scholar]
  12. 12.
    Cichocki JA, Guyton KZ, Guha N, Chiu WA, Rusyn I, Lash LH. 2016.. Target organ metabolism, toxicity, and mechanisms of trichloroethylene and perchloroethylene: key similarities, differences, and data gaps. . J. Pharmacol. Exp. Ther. 359::11023
    [Crossref] [Google Scholar]
  13. 13.
    Lash LH, Fisher JW, Lipscomb JC, Parker JC. 2000.. Metabolism of trichloroethylene. . Environ. Health Perspect. 108: (Suppl. 2):177200
    [Crossref] [Google Scholar]
  14. 14.
    Zhang F, Marty S, Budinsky R, Bartels M, Pottenger LH, et al. 2018.. Analytical methods impact estimates of trichloroethylene's glutathione conjugation and risk assessment. . Toxicol. Lett. 296::8294
    [Crossref] [Google Scholar]
  15. 15.
    Valdiviezo A, Brown GE, Michell A, Trinconi C, Bodke V, et al. 2022.. Re-analysis of trichloroethylene and tetrachloroethylene metabolism to glutathione conjugates using human, rat and mouse liver in vitro models improves precision in risk characterization. . Environ. Health Perspect. 130::117009
    [Crossref] [Google Scholar]
  16. 16.
    Lash LH. 2022.. Improved risk characterization for trichloroethylene and perchloroethylene based on new analyses of glutathione conjugation rates. . Environ. Health Perspect. 130::111307
    [Crossref] [Google Scholar]
  17. 17.
    Lash LH, Parker JC, Scott CS. 2000.. Modes of action of trichloroethylene for kidney tumorigenesis. . Environ. Health Perspect. 108:(Suppl. 2):22540
    [Crossref] [Google Scholar]
  18. 18.
    Chiu WA, Campbell JL Jr., Clewell HJ III, Zhou Y-H, Wright FA, et al. 2014.. Physiologically based pharmacokinetic (PBPK) modeling of interstrain variability in trichloroethylene metabolism in the mouse. . Environ. Health Perspect. 122::45663
    [Crossref] [Google Scholar]
  19. 19.
    Luo Y-S, Furuya S, Soldatov VY, Kosyk O, Yoo HS. 2018.. Metabolism and toxicity of trichloroethylene and tetrachloroethylene in cytochrome P450 2E1 knockout and humanized transgenic mice. . Toxicol. Sci. 164::489500
    [Crossref] [Google Scholar]
  20. 20.
    Luo Y-S, Hsieh N-H, Soldatow VY, Chiu WA, Rusyn I. 2018.. Comparative analysis of metabolism of trichloroethylene and tetrachloroethylene among mouse tissues and strains. . Toxicology 409::3343
    [Crossref] [Google Scholar]
  21. 21.
    Yoo HS, Bradford BU, Kosyk O, Shymonyak S, Uehara T, et al. 2015.. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: liver effects. . J. Toxicol. Environ. Health A 78::1531
    [Crossref] [Google Scholar]
  22. 22.
    Yoo HS, Bradford BU, Kosyk O, Uehara T, Shymonyak S, et al. 2015.. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. . J. Toxicol. Environ. Health A 78::3249
    [Crossref] [Google Scholar]
  23. 23.
    Capinha L, Jennings P, Commandeur JNM. 2021.. Bioactivation of trichloroethylene to three regioisomeric glutathione conjugates by liver fractions and recombinant human glutathione transferases: species differences and implications for human risk assessment. . Toxicol. Lett. 341::94106
    [Crossref] [Google Scholar]
  24. 24.
    Mortuza T, Muralidhara S, White CA, Cummings BS, Hines C, Bruckner JV. 2018.. Effect of dose and exposure protocol on the toxicokinetics and first-pass elimination of trichloroethylene and 1,1,1-trichloroethane. . Toxicol. Appl. Pharmacol. 360::18592
    [Crossref] [Google Scholar]
  25. 25.
    Wang H, Zhang J-X, Ye L-P, Li S-L, Wang F, et al. 2016.. Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice. . J. Immunotoxicol. 13::56779
    [Crossref] [Google Scholar]
  26. 26.
    Yang L, Zhang J, Li N, Xie H, Chen S, et al. 2018.. Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: impact on NF-κB signaling pathway. . J. Immunotoxicol. 15::12636
    [Crossref] [Google Scholar]
  27. 27.
    Wang F, Huang L-P, Yang P, Ye L-P, Wu C, Zhu Q-X. 2019.. Inflammatory kidney injury in trichloroethylene hypersensitivity syndrome mice: possible role of C3a receptor in the accumulation of Th17 phenotype. . Ecotoxicol. Environ. Saf. 186::109772
    [Crossref] [Google Scholar]
  28. 28.
    Liu M, Wang H, Zhang J, Yang X, Li B, et al. 2018.. NF-κB signaling pathway-enhanced complement activation mediates renal injury in trichloroethylene-sensitized mice. . J. Immunotoxicol. 15::6372
    [Crossref] [Google Scholar]
  29. 29.
    Yang X, Xiang W, Huang M, Dai Y, Li B, et al. 2020.. Intracellular complement activation in podocytes aggravates immune kidney injury in trichloroethylene-sensitized mice. . J. Toxicol. Sci. 45::68193
    [Crossref] [Google Scholar]
  30. 30.
    Wang G, Zhang J, Dai Y, Xu Q, Zhu Q. 2020.. Local renal complement activation mediates immune kidney injury by inducing endothelin-1 signalling and inflammation in trichloroethylene-sensitised mice. . Toxicol. Lett. 333::13039
    [Crossref] [Google Scholar]
  31. 31.
    Zhang X, Xie H, Liu Z, Zhang J, Deng L, et al. 2023.. HMGB 1 acetylation mediates trichloroethylene-induced immune kidney injury by facilitating endothelial cell-podocyte communication. . Ecotoxicol. Environ. Saf. 259::115042
    [Crossref] [Google Scholar]
  32. 32.
    Zuo X, Liu Z, Ma J, Ding Y, Cai S, et al. 2022.. Wnt 5a mediated inflammatory injury of renal tubular epithelial cells dependent on calcium signaling pathway in trichloroethylene sensitized mice. . Ecotoxicol. Environ. Saf. 243::114019
    [Crossref] [Google Scholar]
  33. 33.
    Wang F, Dai Y, Huang M, Zhang C, Huang L, et al. 2021.. Glomerular damage in trichloroethylene-sensitized mice: targeting cathepsin L-induced hyperactive mTOR signaling. . Front. Pharmacol. 12::639878
    [Crossref] [Google Scholar]
  34. 34.
    Zhang X, Duan Y, Ma J, Liu Z, Ding Y, et al. 2022.. Trichloroethylene induces immune renal tubular injury through SIRT 1/HSP 70/TLR 4 pathway in BALBc mice. . Int. Immunopharmacol. 112::109203
    [Crossref] [Google Scholar]
  35. 35.
    Li B, Xie H, Wang X, Yang X, Yang L, et al. 2019.. Oxidative stress mediates renal endothelial cell damage in trichloroethylene-sensitized mice. . J. Toxicol. Sci. 44::31726
    [Crossref] [Google Scholar]
  36. 36.
    Xie H, Zhang X, Peng J, Deng L, Wang F, et al. 2022.. Endothelin-1 down-regulated vascular endothelial growth factor A is involved in trichloroethene-induced kidney injury. . Toxicol. Ind. Health 38::28798
    [Crossref] [Google Scholar]
  37. 37.
    Wang Y, Huang M, Du X, Hong Y, Huang L, et al. 2021.. Renal tubular cell necroptosis: a novel mechanism of kidney damage in trichloroethylene hypersensitivity syndrome mice. . J. Immunotoxicol. 18::17382
    [Crossref] [Google Scholar]
  38. 38.
    Xie H, Peng J, Zhang X, Deng L, Ding Y, et al. 2022.. Effects of mitochondrial reactive oxygen species-induced NLRP3 inflammasome activation on trichloroethylene-mediated kidney immune injury. . Ecotoxicol. Environ. Saf. 244::114067
    [Crossref] [Google Scholar]
  39. 39.
    Ma J, Liu Z, Zhou S, Chen M, Gao L. 2022.. Renal tubular in TCE-sensitization-induced immune kidney injury: role of mitochondrial DNA in activating the cGAS-STING signaling pathway. . Int. Immunopharmacol. 113:(Part B):109432
    [Crossref] [Google Scholar]
  40. 40.
    Liu Z, Ma J, Zuo X, Zhang X, Xie H, et al. 2023.. IP3R-dependent mitochondrial dysfunction mediates C5b-9-induced ferroptosis in trichloroethylene-caused immune kidney injury. . Front. Immunol. 14::1106693
    [Crossref] [Google Scholar]
  41. 41.
    Jiang Y, Chen J, Tong J, Chen T. 2014.. Trichloroethylene-induced gene expression and DNA methylation changes in B6C3F1 mouse liver. . PLOS ONE 9:(12):e116179
    [Crossref] [Google Scholar]
  42. 42.
    Jiang Y, Chen J, Tong J, Chen T. 2015.. Transcriptomic profiling of trichloroethylene exposure in male mouse liver. . Genom. Data 3::14042
    [Crossref] [Google Scholar]
  43. 43.
    Jiang Y, Chen J, Yue C, Zhang H, Chen T. 2016.. Trichloroethylene-induced DNA methylation changes in male F344 rat liver. . Chem. Res. Toxicol. 29::177377
    [Crossref] [Google Scholar]
  44. 44.
    Ren F, Wang J, Aniagu S, Li J, Jiang Y, Chen T. 2020.. Effects of trichloroethylene on the expression of long intergenic noncoding RNAs in B6C3F1 mouse liver. . Chem. Res. Toxicol. 33::135663
    [Crossref] [Google Scholar]
  45. 45.
    Venkatratnam A, House JS, Konganti K, McKenney C, Threadgill DW, et al. 2018.. Population-based dose-response analysis of liver transcriptional response to trichloroethylene in mouse. . Mamm. Genome 29::16881
    [Crossref] [Google Scholar]
  46. 46.
    Kopec AK, Sullivan BP, Kassel KM, Joshi N, Luyendyk JP. 2014.. Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in autoimmune-mediated cholangitis in mice. . Toxicol. Sci. 141::51523
    [Crossref] [Google Scholar]
  47. 47.
    Ray JL, Kopec AK, Joshi N, Cline-Fedewa H, Lash LH, et al. 2017.. Trichloroethylene exposure reduces liver injury in a mouse model of primary biliary cholangitis. . Toxicol. Sci. 156::42837
    [Google Scholar]
  48. 48.
    Blossom SJ, Gokulan K, Arnold M, Khare S. 2020.. Sex-dependent effects on liver inflammation and gut microbial dysbiosis after continuous developmental exposure to trichloroethylene in autoimmune-prone mice. . Front. Pharmacol. 11::569008
    [Crossref] [Google Scholar]
  49. 49.
    Zhang J, Li N, Yang L, Zang D, Yang P, et al. 2018.. Role of selective blocking of bradykinin B1 receptor in attenuating immune liver injury in trichloroethylene-sensitized mice. . Cytokine 108::7181
    [Crossref] [Google Scholar]
  50. 50.
    Zhang J, Li N, Yang L, Xie H, Yang Y, et al. 2019.. Bradykinin contributes to immune liver injury via B2R receptor-mediated pathways in trichloroethylene sensitized mice: a role in Kupffer cell activation. . Toxicology 415::3748
    [Crossref] [Google Scholar]
  51. 51.
    Zhang J-X, Yang Y, Huang H, Xie H-B, Huang M, et al. 2022.. TNF-α/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury. . Ecotoxicol. Environ. Saf. 230::113141
    [Crossref] [Google Scholar]
  52. 52.
    Zhang J-X, Xu Q-Y, Yang Y, Li N, Zhang Y, et al. 2020.. Kupffer cell inactivation ameliorates immune liver injury via TNF-α/TNFR1 signal pathway in trichloroethylene sensitized mice. . Immunopharmacol. Immunotoxicol. 42::54555
    [Crossref] [Google Scholar]
  53. 53.
    Zhang J-X, Lia N, Xua Q-Y, Yang Y, Xie H-B, et al. 2020.. Kupffer cell depletion attenuates IL-6/STAT3 mediates hepatocyte apoptosis in immunological liver injury of trichloroethylene sensitized mice. . Int. Immunopharmacol. 88::106897
    [Crossref] [Google Scholar]
  54. 54.
    Zhou S-F, Xu Q-Y, Yang Y, Xie H-B, Zhang J-X, Zhu Q-X. 2023.. The role of Kupffer cell activation in immune liver damage induced by trichloroethylene associated with the IFN-γ/STAT1 signaling pathway. . Toxicol. Ind. Health 39::51527
    [Crossref] [Google Scholar]
  55. 55.
    Ding B, Zhou S, Wang Z, Liu W, Gao L, et al. 2023.. Macrophage autophagy contributes to immune liver injury in trichloroethylene sensitized mice: critical role of TNF-α mediating mTOR pathway. . J. Cell. Physiol. 238::226781
    [Crossref] [Google Scholar]
  56. 56.
    Meadows JR, Parker C, Gilbert KM, Blossom SJ, DeWitt JC. 2017.. A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice. . J. Immunotoxicol. 14::95102
    [Crossref] [Google Scholar]
  57. 57.
    Salama MM, El-Naggar DA, Abdel-Rahman RH, Elhak SAG. 2018.. Toxic effects of trichloroethylene on rat neuroprogenitor cells. . Front. Pharmacol. 9::741
    [Crossref] [Google Scholar]
  58. 58.
    Blossom SJ, Melnyk SB, Li M, Wessinger WD, Cooney CA. 2017.. Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure. . Neurotoxicology 59::16474
    [Crossref] [Google Scholar]
  59. 59.
    Adamson A, Ilieva N, Stone WJ, De Miranda BR. 2023.. Low-dose inhalation exposure to trichloroethylene induces dopaminergic neurodegeneration in rodents. . Toxicol. Sci. 196::21828
    [Crossref] [Google Scholar]
  60. 60.
    Blossom SJ, Melnyk SB, Simmen FA. 2020.. Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice. . Environ. Sci. Process Impacts 22::58394
    [Crossref] [Google Scholar]
  61. 61.
    Yeung JA. 2017.. Unusual case of anxiety: trichloroethylene neurotoxicity. . BMJ Case Rep. 2017::bcr2017223074
    [Crossref] [Google Scholar]
  62. 62.
    De Miranda BR, Greenamyre JT. 2020.. Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson's disease. . Environ. Sci. Process Impacts 22::54354
    [Crossref] [Google Scholar]
  63. 63.
    Nielsen SS, Warden MN, Sallmén M, Sainio M, Uuksulainen S, et al. 2021.. Solvent exposed occupations and risk of Parkinson disease in Finland. . Clin. Parkinsonism Rel. Disorders 4::100092
    [Crossref] [Google Scholar]
  64. 64.
    Dorsey ER, Zafar M, Lettenberger SE, Pawlik ME, Kinel D, et al. 2023.. Trichloroethylene: an invisible cause of Parkinson's disease?. J. Parkinson's Dis. 13::20318
    [Crossref] [Google Scholar]
  65. 65.
    Dorsey ER, Bloem BR. 2024.. Parkinson's disease is predominantly an environmental disease. . J. Parkinson's Dis. 14:(3):45165
    [Crossref] [Google Scholar]
  66. 66.
    Liu M, Shin E-J, Dang D-K, Jin C-H, Lee PH, et al. 2018.. Trichloroethylene and Parkinson's disease: risk assessment. . Mol. Neurobiol. 55::620114
    [Crossref] [Google Scholar]
  67. 67.
    De Miranda BR, Castro SL, Rocha EM, Bodle CR, Johnson KE, Greenamyre JT. 2021.. The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease. . Neurobiol. Dis. 153::105312
    [Crossref] [Google Scholar]
  68. 68.
    Ilieva NM, Wallen ZD, De Miranda BR. 2022.. Oral ingestion of the environmental toxicant trichloroethylene in rats induces alterations in the gut microbiome: relevance to idiopathic Parkinson's disease. . Toxicol. Appl. Pharmacol. 451::116176
    [Crossref] [Google Scholar]
  69. 69.
    Ordaz JD, Damayanti NP, Irudayaraj JMK. 2017.. Toxicological effects of trichloroethylene exposure on immune disorders. . Immunopharmacol. Immunotoxicol. 39::30517
    [Crossref] [Google Scholar]
  70. 70.
    Huang Y-S, Huang H-L, Wu Q-F, Xia L-H, Huang M, et al. 2016.. Follow-up assessment of two cases of trichloroethylene hypersensitivity syndrome: a case report. . Exp. Ther. Med. 12::895900
    [Crossref] [Google Scholar]
  71. 71.
    Nakajima T, Wang H, Ito Y, Naito H, Wang D, et al. 2018.. Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome. . Indus. Health 56::3007
    [Crossref] [Google Scholar]
  72. 72.
    Wang H, Nakajima T, Ito Y, Naito H, Zhao N, et al. 2020.. Increased risk of occupational trichloroethylene hypersensitivity syndrome at exposure levels higher than 15 mg/L of urinary trichloroacetic acid, regardless of whether the patients had the HLA-B*13:01 allele. . Environ. Res. 191::109972
    [Crossref] [Google Scholar]
  73. 73.
    Nakajima T, Wang H, Yuan Y, Ito Y, Naito H. 2022.. Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study. . Arch. Toxicol. 96::278597
    [Crossref] [Google Scholar]
  74. 74.
    Dai Y, Zhou W, Jia Q, Dong H, Niu Y, et al. 2020.. Utility evaluation of HLA-B*13:01 screening in preventing trichloroethylene-induced hypersensitivity syndrome in a prospective cohort study. . Occup. Environ. Med. 77::2016
    [Crossref] [Google Scholar]
  75. 75.
    Jiao B, Liu S, Yi M, Zhang J, Yang HJ, et al. 2022.. Occupational health effect of TCE exposure: experiment evidence of gene-environment interaction in hypersensitivity reaction. . Chem.-Biol. Interact. 368::110220
    [Crossref] [Google Scholar]
  76. 76.
    Blossom SJ, Gilbert KM. 2018.. Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease. . Curr. Opin. Toxicol. 10::2330
    [Crossref] [Google Scholar]
  77. 77.
    Gilbert KM, Blossom SJ, Erickson SW, Reisfeld B, Zurlinden TJ, et al. 2016.. Chronic exposure to water pollutant trichloroethylene increased epigenetic drift in CD4+ T cells. . Epigenomics 8::63349
    [Crossref] [Google Scholar]
  78. 78.
    Gilbert KM, Blossom SJ, Reisfeld B, Erickson SW, Vyas K, et al. 2017.. Trichloroethylene-induced alterations in DNA methylation were enriched in polycomb protein binding sites in effector/memory CD4+ T cells. . Environ. Epigenet. 3::dvx013
    [Crossref] [Google Scholar]
  79. 79.
    Byrum SD, Washam CL, Patterson JD, Vyas KK, Gilbert KM, Blossom SJ. 2019.. Continuous developmental and early life trichloroethylene exposure promoted DNA methylation alterations in polycomb protein binding sites in effector/memory CD4+ T cells. . Front. Immunol. 10::2016
    [Crossref] [Google Scholar]
  80. 80.
    Phillips RV, Rieswijk L, Hubbard AE, Vermeulen R, Zhang J, et al. 2019.. Human exposure to trichloroethylene is associated with increased variability of blood DNA methylation that is enriched in genes and pathways related to autoimmune disease and cancer. . Epigenetics 14::111224
    [Crossref] [Google Scholar]
  81. 81.
    Wang G, Wang J, Luo X, Ansari GAS, Khan MF. 2014.. Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity. . PLOS ONE 9::e98660
    [Crossref] [Google Scholar]
  82. 82.
    Wang H, Wang G, Liang Y, Du X, Boor PJ, et al. 2019.. Redox regulation of hepatic NLRP3 inflammasome activation and immune dysregulation in trichloroethene-mediated autoimmunity. . Free Radic. Biol. Med. 143::22331
    [Crossref] [Google Scholar]
  83. 83.
    Banerjee N, Wang H, Wang G, Khan MF. 2020.. Enhancing the Nrf2 antioxidant signaling provides protection against trichloroethene-mediated inflammation and autoimmune response. . Toxicol. Sci. 175::6474
    [Crossref] [Google Scholar]
  84. 84.
    Wang G, Wang H, Banerjee N, Khan MF. 2020.. Interplay and roles of oxidative stress, toll-like receptor 4 and Nrf2 in trichloroethene-mediated autoimmunity. . Toxicol. Appl. Pharmacol. 408::115258
    [Crossref] [Google Scholar]
  85. 85.
    Pan Y, Wei X, Hao W. 2015.. Trichloroethylene and its oxidative metabolites enhance the activated state and Th1 cytokine gene expression in Jurkat cells. . Int. J. Environ. Res. Public Health 12::1057586
    [Crossref] [Google Scholar]
  86. 86.
    Huang Y, Xia L, Wu Q, Zeng Z, Huang Z, et al. 2015.. Trichloroethylene hypersensitivity syndrome is potentially mediated through its metabolite chloral hydrate. . PLOS ONE 10::e0127101
    [Crossref] [Google Scholar]
  87. 87.
    Wang G, Wakamiya M, Wang J, Ansari GAS, Khan MF. 2019.. Cytochrome P450 2E1-deficient MRL+/+ mice are less susceptible to trichloroethene-mediated autoimmunity: involvement of oxidative stress-responsive signaling pathways. . Free Radic. Biol. Med. 143::32430
    [Crossref] [Google Scholar]
  88. 88.
    Harris SM, Bakulski KM, Dou J, Houskamp E, Scheeres EC, et al. 2022.. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. . Toxicol. In Vitro 84::105429
    [Crossref] [Google Scholar]
  89. 89.
    Banerjee N, Wang H, Wang G, Boor PJ, Khan MF. 2022.. Differential expression of miRNAs in trichloroethene-mediated inflammatory/autoimmune response and its modulation by sulforaphane: delineating the role of miRNA-21 and miRNA-690. . Front. Immunol. 13::868539
    [Crossref] [Google Scholar]
  90. 90.
    Khare S, Gokulan K, Williams K, Bai S, Gilbert KM, Blossom SJ. 2019.. Irreversible effects of trichloroethylene on the gut microbial community and gut associated immune responses in autoimmune-prone mice. . J. Appl. Toxicol. 39::20920
    [Crossref] [Google Scholar]
  91. 91.
    Wang H, Banerjee N, Liang Y, Wang G, Hoffman KL, Khan MF. 2021.. Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity. . Toxicol. Appl. Pharmacol. 424::115597
    [Crossref] [Google Scholar]
  92. 92.
    Makris SL, Scott CS, Fox J, Knudsen TB, Hotchkiss AK, et al. 2016.. A systematic evaluation of the potential effects of trichloroethylene exposure on cardiac development. . Reprod. Toxicol. 65::32158
    [Crossref] [Google Scholar]
  93. 93.
    Urban JD, Wikoff DS, Chappell GA, Harris C, Haws LC. 2020.. Systematic evaluation of mechanistic data in assessing in utero exposures to trichloroethylene and development of congenital heart defects. . Toxicology 436::152427
    [Crossref] [Google Scholar]
  94. 94.
    Jiang Y, Wang D, Zhang G, Wang G, Tong J, Chen T. 2016.. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene. . Environ. Toxicol. 31::137280
    [Crossref] [Google Scholar]
  95. 95.
    Harris AP, Ismail KA, Nunez M, Martopullo I, Lencinas A, et al. 2018.. Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart. . Toxicol. Lett. 285::11320
    [Crossref] [Google Scholar]
  96. 96.
    Chen S, Lencinas A, Nunez M, Selmin OI, Runyan RB. 2020.. HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart. . Environ. Sci. Process Impacts 22::82432
    [Crossref] [Google Scholar]
  97. 97.
    Jin H, Ji C, Ren F, Aniagu S, Tong J, et al. 2020.. AHR-mediated oxidative stress contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish embryos. . J. Hazard. Mater. 385::121521
    [Crossref] [Google Scholar]
  98. 98.
    Huang Y, Jiang B, Xia Y, Wang J, Ji C, et al. 2020.. Downregulation of miR-133a contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish. . Chemosphere 251::126610
    [Crossref] [Google Scholar]
  99. 99.
    Iritas SB, Dip A, Gunduzoz M, Tutkun L, Tu VA, et al. 2021.. Assessment of potential cardiovascular risk in trichloroethylene exposure by serum methylated arginine levels. . Int. J. Environ. Health Res. 31::6374
    [Crossref] [Google Scholar]
  100. 100.
    Dumasa O, Despreaux T, Perros F, Lau E, Andujar P. 2018.. Respiratory effects of trichloroethylene. . Respir. Med. 134::4753
    [Crossref] [Google Scholar]
  101. 101.
    Asif H, Braman SS. 2024.. Combined pulmonary fibrosis and emphysema in a patient with chronic occupational exposure to trichloroethylene. . Mil. Med. 189:(3–4):e90710
    [Crossref] [Google Scholar]
  102. 102.
    Loch-Caruso R, Hassan I, Harris SM, Kumar A, Bjork F, Lash LH. 2019.. Trichloroethylene exposure in mid-pregnancy decreased fetal weight and increased placental markers of oxidative stress in rats. . Reprod. Toxicol. 83::3845
    [Crossref] [Google Scholar]
  103. 103.
    Horzmann KA, Portales AM, Batcho KG, Freeman JL. 2020.. Developmental toxicity of trichloroethylene in zebrafish (Danio rerio). . Environ. Sci. Process Impacts 22::728
    [Crossref] [Google Scholar]
  104. 104.
    Tachachartvanich P, Sangsuwan R, Ruiz HS, Sanchez SS, Durkin KA, et al. 2018.. Assessment of the endocrine-disrupting effects of trichloroethylene and its metabolites using in vitro and in silico approaches. . Environ. Sci. Technol. 52::154250
    [Crossref] [Google Scholar]
  105. 105.
    Harris SM, Boldenow E, Domino SE, Loch-Caruso R. 2020.. Toxicant disruption of immune defenses: potential implications for fetal membranes and pregnancy. . Front. Physiol. 11::565
    [Crossref] [Google Scholar]
  106. 106.
    Elkin ER, Harris SM, Su AL, Lash LH, Loch-Caruso R. 2020.. Placenta as a target of trichloroethylene toxicity. . Environ. Sci. Process Impacts 22::47286
    [Crossref] [Google Scholar]
  107. 107.
    Elkin ER, Su AL, Kilburn BA, Bakulski KM, Armant DR, Loch-Caruso R. 2022.. Toxicity assessments of selected trichloroethylene and perchloroethylene metabolites in three in vitro human placental models. . Reprod. Toxicol. 109::10920
    [Crossref] [Google Scholar]
  108. 108.
    Boldenow E, Hassan I, Chames MC, Xi C, Loch-Caruso R. 2015.. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro. . Reprod. Toxicol. 52::16
    [Crossref] [Google Scholar]
  109. 109.
    Hassan I, Kumar AM, Park H-R, Lash LH, Loch-Caruso R. 2016.. Reactive oxygen stimulation of interleukin-6 release in the human trophoblast cell line HTR-8/SVneo by the trichlorethylene metabolite S-(1,2-dichloro)-L-cysteine. . Biol. Reprod. 95::66
    [Crossref] [Google Scholar]
  110. 110.
    Elkin ER, Bridges D, Loch-Caruso R. 2019.. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine induces progressive mitochondrial dysfunction in HTR-8/SVneo trophoblasts. . Toxicology 427::152283
    [Crossref] [Google Scholar]
  111. 111.
    Su AL, Loch-Caruso R. 2023.. Apoptotic responses stimulated by the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine depend on cell differentiation state in BeWo human trophoblast cells. . Toxicol. In Vitro 86::105514
    [Crossref] [Google Scholar]
  112. 112.
    Su AL, Harris SM, Elkin ER, Karnovsky A, Colacino J, Loch-Caruso RK. 2023.. Trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine stimulates changes in energy metabolites and amino acids in the BeWo human placental trophoblast model during syncytialization. . Chem. Res. Toxicol. 36::88299
    [Crossref] [Google Scholar]
  113. 113.
    Lash LH. 2022.. Cellular biomarkers of renal injury. . Curr. Opin. Toxicol. 31::100348
    [Crossref] [Google Scholar]
  114. 114.
    Lash LH, Stemmer PM. 2021.. Renal mitochondria as sentinels for exposures to environmental toxicants and nephrotoxic drugs. . In Toxicological Risk Assessment and Multi-System Health Impacts from Exposure, ed. A Tsatsakis , pp. 17587. Amsterdam:: Elsevier
    [Google Scholar]
  115. 115.
    Lash LH. 2021.. Diverse roles of mitochondria in renal injury from environmental toxicants and therapeutic drugs. . Int. J. Mol. Sci. 22::4172
    [Crossref] [Google Scholar]
  116. 116.
    Walker DI, Uppal K, Zhang L, Vermeulen R, Smith M, et al. 2016.. High-resolution metabolomics of occupational exposure to trichloroethylene. . Int. J. Epidemiol. 45::151727
    [Crossref] [Google Scholar]
  117. 117.
    Huang P, Ren X, Huang Z, Yang X, Hong W, et al. 2014.. Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene. . Toxicol. Lett. 229::10110
    [Crossref] [Google Scholar]
  118. 118.
    Bassig BA, Zhang L, Vermeulen R, Tang X, Li G, et al. 2016.. Comparison of hematological alterations and markers of B-cell activation in workers exposed to benzene, formaldehyde and trichloroethylene. . Carcinogenesis 37::692700
    [Crossref] [Google Scholar]
  119. 119.
    Hosgood HD, Rahman ML, Blansky D, Hu W, Davitt M, et al. 2022.. Targeted proteomic scan identifies alteration of serum proteins among workers occupationally exposed to low levels of trichloroethylene. . Environ. Mol. Mutagen. 63::42328
    [Crossref] [Google Scholar]
  120. 120.
    Lee K-M, Bassig BA, Zhang L, Vermeulen RC, Hu W, et al. 2019.. Associations between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China. . Int. Arch. Occup. Environ. Health 92::107785
    [Crossref] [Google Scholar]
  121. 121.
    Capinha L, Zhang Y, Holzer A-K, Holzer A-K, Ückert A-K, Zana M. 2023.. Transcriptomic-based evaluation of trichloroethylene glutathione and cysteine conjugates demonstrate phenotype-dependent stress responses in a panel of human in vitro models. . Arch. Toxicol. 97::52345
    [Crossref] [Google Scholar]
  122. 122.
    Kim I, Ha J, Lee J-H, Yoo K-M, Rho J. 2014.. The relationship between the occupational exposure of trichloroethylene and kidney cancer. . Ann. Occup. Environ. Med. 26::12
    [Crossref] [Google Scholar]
  123. 123.
    Buhagen M, Grønskag A, Ragde SF, Hilt B. 2016.. Association between kidney cancer and occupational exposure to trichloroethylene. . J. Occup. Environ. Med. 58::95759
    [Crossref] [Google Scholar]
  124. 124.
    Landskroner EA, Tsai CS-J. 2023.. Occupational exposures and cancer risk in commercial laundry and dry-cleaning industries: a scoping review. . BMC Public Health 23::2561
    [Crossref] [Google Scholar]
  125. 125.
    Alanee S, Clemons J, Zahnd W, Sadowski D, Dynda D. 2015.. Trichloroethylene is associated with kidney cancer mortality: a population-based analysis. . Anticancer Res. 35::400914
    [Google Scholar]
  126. 126.
    Andrew AS, Li M, Shi X, Rees JR, Craver KM, Petali JM. 2022.. Kidney cancer risk associated with historic groundwater trichloroethylene contamination. . Int. J. Environ. Res. Public Health 19::618
    [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-022724-120525
Loading
/content/journals/10.1146/annurev-pharmtox-022724-120525
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error