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Sangyo Eiseigaku Zasshi = Journal of... Jul 2023To provide an overview of the pathogenesis of pneumatosis cystoides intestinalis (PCI) and hypersensitivity syndrome (HS) caused by trichloroethylene (TCE) and the basic... (Review)
Review
OBJECTIVE
To provide an overview of the pathogenesis of pneumatosis cystoides intestinalis (PCI) and hypersensitivity syndrome (HS) caused by trichloroethylene (TCE) and the basic research into their toxicity.
SUBJECTS AND METHODS
We reviewed previously published research articles.
RESULTS
PCI clustered in Japan in the 1980s is a rare disease characterized by cyst-like distention of gas in the intestinal wall, which can be secondary or primary. No TCE users were found in the former group, whereas approximately 71% of the latter group were TCE users, suggesting the involvement of TCE exposure in primary PCI. However, the pathogenesis was unclear. TCE is metabolized by the drug-metabolizing enzyme CYP2E1, and intermediate immunocomplexes with CYP2E1 may be involved in hepatotoxicity. HS clustered in the southern part of China since early 2000 is a systemic skin-liver disorder involving anti-CYP2E1 autoantibodies and HLA-B*13:01 polymorphisms, with elevated cytokines and reactivation of Human Herpesvirus 6.
DISCUSSION AND CONCLUSION
PCI and HS, occupational diseases caused by TCE, were clustered in Japan and southern China, respectively. HS was mediated by immune system disorders and genetic polymorphisms, whereas their relevance to PCI occurrence remained unknown.
Topics: Humans; Trichloroethylene; Occupational Diseases; Drug Hypersensitivity Syndrome; Skin Diseases; Liver
PubMed: 37211415
DOI: 10.1539/sangyoeisei.2023-010-A -
Environmental Health Perspectives Sep 2006Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE) . Qualitatively, it is clear that TCE is metabolized to multiple... (Review)
Review
Much progress has been made in understanding the complex pharmacokinetics of trichloroethylene (TCE) . Qualitatively, it is clear that TCE is metabolized to multiple metabolites either locally or into systemic circulation. Many of these metabolites are thought to have toxicologic importance. In addition, efforts to develop physiologically based pharmacokinetic (PBPK) models have led to a better quantitative assessment of the dosimetry of TCE and several of its metabolites. As part of a mini-monograph on key issues in the health risk assessment of TCE, this article is a review of a number of the current scientific issues in TCE pharmacokinetics and recent PBPK modeling efforts with a focus on literature published since 2000. Particular attention is paid to factors affecting PBPK modeling for application to risk assessment. Recent TCE PBPK modeling efforts, coupled with methodologic advances in characterizing uncertainty and variability, suggest that rigorous application of PBPK modeling to TCE risk assessment appears feasible at least for TCE and its major oxidative metabolites trichloroacetic acid and trichloroethanol. However, a number of basic structural hypotheses such as enterohepatic recirculation, plasma binding, and flow- or diffusion-limited treatment of tissue distribution require additional evaluation and analysis. Moreover, there are a number of metabolites of potential toxicologic interest, such as chloral, dichloroacetic acid, and those derived from glutathione conjugation, for which reliable pharmacokinetic data is sparse because of analytical difficulties or low concentrations in systemic circulation. It will be a challenge to develop reliable dosimetry for such cases.
Topics: Environmental Exposure; Environmental Pollutants; Hazardous Substances; History, 21st Century; Humans; Neoplasms; Risk Assessment; Risk Factors; Time Factors; Trichloroethylene; United States
PubMed: 16966104
DOI: 10.1289/ehp.8691 -
International Journal of Environmental... Jan 2022Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from...
Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases ( = 292) and age-, gender-matched controls ( = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th-75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05-3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.
Topics: Animals; Groundwater; Kidney; Kidney Neoplasms; Solvents; Trichloroethylene
PubMed: 35055441
DOI: 10.3390/ijerph19020618 -
The Science of the Total Environment Apr 2022Chlorinated solvents occur as dense nonaqueous phase liquid (DNAPL) or as solutes when dissolved in water. They are present in many pollution sites in urban and...
Chlorinated solvents occur as dense nonaqueous phase liquid (DNAPL) or as solutes when dissolved in water. They are present in many pollution sites in urban and industrial areas. They are toxic, carcinogenic, and highly recalcitrant in aquifers and aquitards. In the latter case, they migrate by molecular diffusion into the matrix. When aquitards are fractured, chlorinated solvents also penetrate as a free phase through the fractures. The main objective of this study was to analyze the biogeochemical processes occurring inside the matrix surrounding fractures and in the joint-points zones. The broader implications of this objective derive from the fact that, incomplete natural degradation of contaminants in aquitards generates accumulation of daughter products. This causes steep concentration gradients and back-diffusion fluxes between aquitards and high hydraulic conductivity layers. This offers opportunities to develop remediation strategies based, for example, on the coupling of biotic and reactive abiotic processes. The main results showed: 1) Degradation occurred especially in the matrix adjacent to the orthogonal network of fractures and textural heterogeneities, where texture contrasts favored microbial development because these zones constituted ecotones. 2) A dechlorinating bacterium not belonging to the Dehalococcoides genus, namely Propionibacterium acnes, survived under the high concentrations of dissolved perchloroethene (PCE) in contact with the PCE-DNAPL and was able to degrade it to trichloroethene (TCE). Dehalococcoides genus was able to conduct PCE reductive dechlorination at least up to cis-1,2-dichloroethene (cDCE), which shows again the potential of the medium to degrade chloroethenes in aquitards. 3) Degradation of PCE in the matrix resulted from the coupling of reactive abiotic and biotic processes-in the first case, promoted by Fe sorbed to iron oxides, and in the latter case, related to dechlorinating microorganisms. The dechlorination resulting from these coupling processes is slow and limited by the need for an adequate supply of electron donors.
Topics: Biodegradation, Environmental; Chlorine; Groundwater; Trichloroethylene; Vinyl Chloride; Water Pollutants, Chemical
PubMed: 34752872
DOI: 10.1016/j.scitotenv.2021.151532 -
Environmental Health Perspectives May 2000Alternatives for developing chronic exposure limits for noncancer effects of trichloroethylene (TCE) were evaluated. These alternatives were organized within a framework... (Review)
Review
Alternatives for developing chronic exposure limits for noncancer effects of trichloroethylene (TCE) were evaluated. These alternatives were organized within a framework for dose-response assessment--exposure:dosimetry (pharmacokinetics):mode of action (pharmacodynamics): response. This framework provides a consistent structure within which to make scientific judgments about available information, its interpretation, and use. These judgments occur in the selection of critical studies, internal dose metrics, pharmacokinetic models, approaches for interspecies extrapolation of pharmacodynamics, and uncertainty factors. Potentially limiting end points included developmental eye malformations, liver effects, immunotoxicity, and kidney toxicity from oral exposure and neurological, liver, and kidney effects by inhalation. Each end point was evaluated quantitatively using several methods. Default analyses used the traditional no-observed adverse effect level divided by uncertainty factors and the benchmark dose divided by uncertainty factors methods. Subsequently, mode-of-action and pharmacokinetic information were incorporated. Internal dose metrics were estimated using a physiologically based pharmacokinetic (PBPK) model for TCE and its major metabolites. This approach was notably useful with neurological and kidney toxicities. The human PBPK model provided estimates of human exposure doses for the internal dose metrics. Pharmacodynamic data or default assumptions were used for interspecies extrapolation. For liver and neurological effects, humans appear no more sensitive than rodents when internal dose metrics were considered. Therefore, the interspecies uncertainty factor was reduced, illustrating that uncertainty factors are a semiquantitative approach fitting into the organizational framework. Incorporation of pharmacokinetics and pharmacodynamics can result in values that differ significantly from those obtained with the default methods.
Topics: Administration, Inhalation; Administration, Oral; Animals; Dose-Response Relationship, Drug; Eye Abnormalities; Hazardous Substances; Humans; Kidney; Nervous System; Risk Assessment; Trichloroethylene
PubMed: 10807562
DOI: 10.1289/ehp.00108s2323 -
Ecotoxicology and Environmental Safety Jul 2023More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage....
More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage. However, the exact mechanisms of cell-to-cell transmission in TCE-induced immune kidney damage remain poorly understood. The present study aimed to explore the role of high mobility group box-1 (HMGB 1) in glomerular endothelial cell-podocyte transmission. 17 OMDT patients and 34 controls were enrolled in this study. We observed that OMDT patients had renal function injury, endothelial cell activation and podocyte injury, and these indicators were associated with serum HMGB 1. To gain mechanistic insight, a TCE-sensitized BALB/c mouse model was established under the interventions of sirtuin 1 (SIRT 1) activator SRT 1720 (0.1 ml, 5 mg/kg) and receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM 1 (0.1 ml, 1.5 mg/kg). We identified HMGB 1 acetylation and its endothelial cytoplasmic translocation following TCE sensitization, but SRT 1720 abolished the process. RAGE was located on podocytes and co-precipitated with extracellular acetylated HMGB 1, promoting podocyte injury, while SRT 1720 and FPS-ZM 1 both alleviated podocyte injury. The results demonstrate that interventions to upstream and downstream pathways of HMGB 1 may weaken glomerular endothelial cell-podocyte transmission, thereby alleviating TCE-induced immune renal injury.
Topics: Animals; Mice; Acetylation; Endothelial Cells; HMGB Proteins; Kidney; Kidney Diseases; Mice, Inbred BALB C; Podocytes; Trichloroethylene; Cell Communication
PubMed: 37216866
DOI: 10.1016/j.ecoenv.2023.115042 -
Environmental Health Perspectives Aug 1998This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their... (Review)
Review
This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p = 0.0004 Wilcoxon test and p =0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.
Topics: Abnormalities, Drug-Induced; Animals; Dichloroethylenes; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Environmental Exposure; Female; Heart; Heart Defects, Congenital; Pregnancy; Pregnancy Complications; Rats; Trichloroethylene
PubMed: 9703484
DOI: 10.1289/ehp.98106s4995 -
Reproductive Toxicology (Elmsford, N.Y.) Oct 2016The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along... (Review)
Review
The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties.
Topics: Animals; Dose-Response Relationship, Drug; Environmental Exposure; Environmental Pollutants; Epithelial-Mesenchymal Transition; Female; Heart; Humans; Pregnancy; Prenatal Exposure Delayed Effects; Solvents; Trichloroethylene
PubMed: 27575429
DOI: 10.1016/j.reprotox.2016.08.014 -
Environmental Science. Processes &... Mar 2020Trichloroethylene (TCE) is an industrial solvent and a common environmental contaminant detected in thousands of hazardous waste sites. Risk of exposure is a concern for...
Trichloroethylene (TCE) is an industrial solvent and a common environmental contaminant detected in thousands of hazardous waste sites. Risk of exposure is a concern for workers in occupations that use TCE as well as for residents who live near industries that use TCE or who live near TCE-contaminated sites. Although renal, hepatic and carcinogenic effects of TCE have been documented, less is known about TCE impacts on reproductive functions despite epidemiology reports associating maternal TCE exposure with adverse pregnancy outcomes. Toxicological evidence suggests that the placenta mediates at least some of the adverse pregnancy outcomes associated with TCE exposure. Toxicology studies show that the TCE metabolite, S-(1,2-dichlorovinyl)-l-cysteine (DCVC) generates toxic effects such as mitochondrial dysfunction, apoptosis, oxidative stress, and release of prostaglandins and pro-inflammatory cytokines in placental cell lines. Each of these mechanisms of toxicity have significant implications for placental functions and, thus, ultimately the health of mother and developing child. Despite these findings there remain significant gaps in our knowledge about effects of TCE on the placenta, including effects on specific placental cell types and functions as well as sex differences in response to TCE exposure. Due to the critical role that the placenta plays in pregnancy, future research addressing some of these knowledge gaps could lead to significant gains in public health.
Topics: Child; Cysteine; Female; Humans; Male; Oxidative Stress; Placenta; Pregnancy; Solvents; Trichloroethylene
PubMed: 32022077
DOI: 10.1039/c9em00537d -
Water Research Mar 2023The use of surfactants represents a viable strategy to boost the removal yield of Dense Non-Aqueous Phase Liquids (DNAPLs) from groundwater and to shorten the...
The use of surfactants represents a viable strategy to boost the removal yield of Dense Non-Aqueous Phase Liquids (DNAPLs) from groundwater and to shorten the operational timing of the remediation process. Surfactants, in general, help in reducing the interfacial tension at the DNAPL/water interface and enhance the solubility of the pollutant in the water phase through the formation of dispersed systems, such as micelles and emulsions. In this paper, we show that a suitable choice of a surfactant, in this case belonging to the bio-degradable class of ethoxylated alcohols, allows for the formation of hydrodynamic interfacial instabilities that further enhances the dissolution rate of the organic pollutant into the water phase. In a stratified configuration (denser organic phase at the bottom and lighter water phase on top), the instabilities appear as upward-pointing fingers that originate from the inversion of the local density at the interface. This inversion stems from the synergetic coupling of two effects promoted by the ethoxylated surfactant: i) the enhanced co-solubility of the DNAPL into the water (and viceversa), and (ii) the differential diffusion of the DNAPL and the surfactant in the aqueous phase. By dissolving into the DNAPL, the surfactant also reduces locally the surface tension at the liquid-liquid interface, thereby inducing transversal Marangoni flows. In our work, we carefully evaluated the effects of the concentration of different surfactants (two different ethoxylated alcohols, sodium dodecylsulphate, cetyltrimethyl ammonium bromide, N-tetradecyl-N, N-dimethylamine oxide and bis(2-ethylhexyl) sulfosuccinate sodium salt) on the onset of the instabilities in 3 different DNAPLs/water stratifications, namely chloroform, trichloroethylene and tetrachloroethylene, with a special emphasis on the trichloroethylene/water system. By means of a theoretical model and nonlinear simulations, supported by surface tension, density and diffusivity measurements, we could provide a solid explanation to the observed phenomena and we found that the type of the dispersed system, the solubility of the DNAPL into the water phase, the solubility of the surfactant in the organic phase, as well as the relative diffusion and density of the surfactant and the DNAPL in the aqueous phase, are all key parameters for the onset of the instabilities. These results can be exploited in the most common remediation techniques.
Topics: Trichloroethylene; Solubility; Water Pollutants, Chemical; Alcohols; Surface-Active Agents; Sodium
PubMed: 36709564
DOI: 10.1016/j.watres.2023.119608