Toxicity Of Trichloroethylene Research Articles

Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.

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.

Controlling aging processes during bio-syngas methanation: SSITKA experiments over Ni/Al2O3 catalysts

A major barrier in the commercialization of biomass or waste gasification into bio-syngas is the presence of impurities such as NH3, HCl, tars and alkali in the products, being detrimental to downstream processes like the conversion of bio-syngas to substitute natural gas. The exact role and effects of these biomass-derived impurities on methanation catalysts are not clearly documented, especially when poisoning factors can combine with structural aging processes such as metal sintering under operating conditions. In order to unravel these aging phenomena under methanation conditions, the direct observation of Steady-State Isotopic Transient Kinetic Analysis curves semi-log transforms is combined with their modeling in view to evaluate the efficiency and sensitivity of this transient kinetic analysis. Thus, the toxicity of acetonitrile, trichloroethylene and toluene as representative of N-, Cl-, C- based poisons respectively, is shown to be strongly linked to the metal dispersion for the studied case of alumina supported nickel catalysts. A rationale linking such a transient kinetic analysis to methanation mechanisms is proposed in the present paper.

Trichloroethylene-induced Cellular Damage was Associated with Significant changes in the Concentrations of Caspase-3 and Glutathione in human lymphocytes

Trichloroethylene (TCE) is a volatile organic compound that is widely used in industries and potential source of environmental contamination. The aims of this study were focused on the effects of TCE on cellular viability and evaluation of critical markers like caspase-3 and glutathione (GSH) in human lymphocytes. The experiments were studied in thirty volunteers. The TCE concentrations of 0.002, 0.004, 0.008, 0.016 and 0.032 mM/L were treated in human lymphocytes for 48 h. Lymphocytes were cultured and effect of TCE on viability of lymphocytes was studied by MTT assay. The expression of caspase-3 in TCE treated lymphocytes was studied by ELISA and the concentration of glutathione in TCE treated lymphocytes was studied by colorimetric technique. The results showed that, in the experimental groups at various TCE concentrations had lower cellular viability than the control group (p<0.05). The caspase-3 concentration was increased when TCE concentration increased (p<0.05). The glutathione concentration was decreased when TCE concentration increased (p<0.05). It is indicated that TCE effected on cellular viability. The expression of caspase-3 enzyme and glutathione concentrations were changed by TCE toxicity in lymphocytes.

Histopathological Studies On The Liver Of Rats Exposed With Toluene And Trichloroethylene Pre-Treated With Phenobarbital

In rats, the effect of phenobarbital Pre-treatment on the toxicity of a variety of halogenated organic solvent has been investigated. The current findings show that Phenobarbital pre- treatment significantly reduces the toxicity of toluene and trichloroethylene. Our observations Show that toluene is more hepatotoxic than trichloroethylene. It causes peculiar ultra-structural changes i.e. involution of nuclear membrane and irregular arrangement of mitochondrial cristae. However, using single high- dose levels of these solvents, a potentiating impact of Phenobarbital on the toxicity of other organic solvents such as methanol, xylene, and methylene chloridecould not be demonstrated. Because barbiturates are commonly used by industrial workers, it’s crucial to be aware of the possibility of synergistic effect from inhaling of organic solvents, as well as of potentiation associated with others.

The role of epigenetic effect in the trichloroethylene toxicity

Trichloroethylene (TCE) is a commonly used organic solvent in industry and it was classified as a Group I carcinogen by IARC, with immunotoxicity, hepatotoxicity, kidney toxicity and neurotoxicity. Increasing evidence suggests that TCE-induced autoimmune diseases and cancer are involved in epigenetic modifications. This paper summarized the mechanism of DNA methylation, histone modification and microRNA in toxicity of TCE according to the newly published articles, so as to provide new ideas for further revealing the mechanism of TCE exposure affecting health.

Mycoremediation of Soils Polluted with Trichloroethylene: First Evidence of Pleurotus Genus Effectiveness

Trichloroethylene (TCE) is a proven carcinogenic chlorinated organic compound widely used as a solvent in industrial cleaning solutions; it is easily found in the soil, air, and water and is a hazardous environmental pollutant. Most studies have attempted to remove TCE from air and water using different anaerobic bacteria species. In addition, a few have used white-rot fungi, although there are hardly any in soil. The objective of the present work is to assess TCE removal efficiency using two species of the genus Pleurotus that have not been tested before: Pleurotus ostreatus and Pleurotus eryngii, growing on a sandy loam soil. These fungi presented different intra- and extracellular enzymatic systems (chytochrome P450 (CYP450), laccase, Mn peroxidase (MnP)) capable of aerobically degrading TCE to less harmful compounds. The potential toxicity of TCE to P. ostreatus and P. eryngii was firstly tested in a TCE-spiked liquid broth (70 mg L−1 and 140 mg L−1) for 14 days. Then, both fungi were assessed for their ability to degrade the pollutant in sandy loam soil spiked with 140 mg kg−1 of TCE. P. ostreatus and P. eryngii improved the natural dissipation of TCE from soil by 44%. Extracellular enzymes were poorly expressed, but mainly in the presence of the contaminant, in accordance with the hypothesis of the involvement of CYP450.

Protective effects of resveratrol against the cardiac developmental toxicity of trichloroethylene in zebrafish embryos

Trichloroethylene (TCE), a prevalent environmental contaminant, has been shown to induce cardiac malformations. Resveratrol (RSV) is a natural polyphenolic compound exhibiting protective effects on heart development. To investigate if RSV could protect against TCE-induced heart defects, we exposed zebrafish embryos to TCE (10 ppb) in the presence or absence of RSV (1 μg/mL). Our results showed that RSV significantly attenuated TCE-induced heart defects in zebrafish embryos. The TCE-induced ROS (reactive oxygen species) generation, 8-OHdG (8-hydroxy-2`-deoxyguanosine) formation and cell proliferation were significantly counteracted by RSV. Moreover, RSV attenuated the TCE-induced changes in mRNA expression or activity of genes involved in AHR and Nrf2 signal pathways. We further showed that RSV might inhibit TCE-enhanced cell proliferation by rescuing the downregulation of the p53/p21 axis. In conclusion, our data demonstrates that RSV protects against the cardiac developmental toxicity of TCE by inhibiting AHR activity, oxidative stress and cell proliferation.

Study on the community structure and function of anaerobic granular sludge under trichloroethylene stress.

Trichloroethylene (TCE) is one of the most common groundwater pollutants. It is carcinogenic, teratogenic, mutagenic and poses a serious threat to human health and the environment. Therefore, reducing the environmental toxicity of TCE is of great significance. Anaerobic sludge was cultured and acclimated in an upflow anaerobic sludge blanket (UASB) reactor in this study. The Chemical Oxygen Demand (COD) concentration of the influent was approximately 2500 mg L-1, and the TCE concentration of the influent ranged from 1.46 mg L-1 to 73 mg L-1. After biodegradation of the anaerobic microflora, the COD removal rate was approximately 85%, and the TCE removal rate was over 85%. The microbial community of anaerobic sludge was analysed by 16 S rDNA clone libray and 454 high-throughput sequencing. Through analysis of the sequencing results, we found that there were a variety of acid-forming bacteria, anaerobic dechlorinating bacteria, and methanogenic bacteria. Based on the analysis of microflora function, it was speculated that the TCE metabolic pathway took place in UASB reactors. Desulfovibrio and Syntrophobacter provided an anaerobic environment, and acid-forming bacteria metabolise organic compounds into hydrogen. With Dehalobacter and Geobacter, TCE as an electron acceptor is dechlorinated and reduced under the anaerobic environment, in which hydrogen acts as an electron donor. By this, we clarified the metabolic pathway for improving TCE bioremediation.

Downregulation of miR-133a contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish

Trichloroethylene (TCE), a widely used organic solvent, is a common environmental pollutant. Increasing evidence indicates that maternal TCE exposure is associated with congenital cardiac defects, but the underlining mechanisms remain largely unknown. In this study, we revealed that TCE exposure significantly induced heart defects and dysfunctions in zebrafish embryos. Heart tissues were dissected and subjected to high throughput sequencing and qPCR to identify differentially expressed miRNAs and mRNAs. The effects of miRNA were further verified by microinjection of antagomir or agomir. Reactive Oxygen Species (ROS) and cell proliferation were measured by using dichlorodihydrofluorescein diacetate (DCFH-DA) and EdU staining, respectively. Our results showed that 19 miRNAs were downregulated whereas 48 miRNAs were upregulated in the heart of zebrafish embryos. The downregulation of miR-133a and the upregulation of miR-182 were further validated. Moreover, we found that miR-133a agomir significantly alleviated the TCE-induced heart defects while miR-133a antagomir mimicked the toxic effect of TCE on heart development. Furthermore, miR-133a agomir significantly counteracted TCE-induced ROS production and excessive cell proliferation in the heart of zebrafish embryos. In conclusion, our results indicate that miR-133a mediates TCE-induced ROS generation, leading to excessive cell proliferation and heart defects.

The Beneficial Effects of Vitamin D3 Against Trichloroethylene Toxicity in Rat Ovaries

The Beneficial Effects of Vitamin D3 Against Trichloroethylene Toxicity in Rat Ovaries

Placenta as a target of trichloroethylene toxicity

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.

HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart.

In exploration of congenital heart defects produced by TCE, Hepatocyte Nuclear Factor 4 alpha (HNF4a) transcriptional activity was identified as a central component. TCE exposure altered gene transcription in the chick heart in a non-monotonic pattern where only low dose exposure inhibited transcription by HNF4a. As the chick embryo is non-placental, we examine here HNF4a as a target of TCE in developing mouse embryos. Benfluorex and Bi6015, published agonist and antagonist, respectively, of HNF4a were compared to low dose TCE exposure. Pregnant mice were exposed to 10 ppb (76 nM) TCE, 5 μM Benfluorex, 5 μM Bi6015, or a combination of Bi6015 and TCE in drinking water. Litters (E12) were collected during a sensitive window in heart development. Embryonic hearts were collected, pooled for extraction of RNA and marker expression was examined by quantitative PCR. Multiple markers, previously identified as sensitive to TCE exposure in chicks or as published targets of HNF4a transcription were significantly affected by Benfluorex, Bi6015 and TCE. Activity of TCE and both HNF4a-specific reagents on transcription argues that HNF4a is a component of TCE cardiotoxicity and likely a proximal target of low dose exposure during development. The effectiveness of these reagents after delivery in maternal drinking water suggests that neither maternal metabolism, nor placental transport is protective of exposure.

AHR-mediated oxidative stress contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish embryos

Trichloroethylene (TCE), a widely used chlorinated solvent, is a common environmental pollutant. Current evidence shows that TCE could induce heart defects during embryonic development, but the underlining mechanism(s) remain unclear. Since activation of the aryl hydrocarbon receptor (AHR) could induce oxidative stress, we hypothesized that AHR-mediated oxidative stress may play a role in the cardiac developmental toxicity of TCE. In this study, we found that the reactive oxygen species (ROS) scavenger, N-Acetyl-L-cysteine (NAC), and AHR inhibitors, CH223191 (CH) and StemRegenin 1, significantly counteracted the TCE-induced heart malformations in zebrafish embryos. Moreover, both CH and NAC suppressed TCE-induced ROS and 8-OHdG (8-hydroxy-2′ -deoxyguanosine). TCE did not affect ahr2 and cyp1a expression, but increased cyp1b1 expression, which was restored by CH supplementation. CH also attenuated the TCE-induced mRNA expression changes of Nrf2 signalling genes (nrf2b, gstp2, sod2, ho1, nqo1) and cardiac differentiation genes (gata4, hand2, c-fos, sox9b). In addition, the TCE enhanced SOD activity was attenuated by CH. Morpholino knockdown confirmed that AHR mediated the TCE-induced ROS and 8-OHdG generation in the heart of zebrafish embryos. In conclusion, our results suggest that AHR mediates TCE-induced oxidative stress, leading to DNA damage and heart malformations in zebrafish embryos.

Trichloroethylene interferes with heart development of zebrafish via inhibiting Wnt signal pathway

To investigate the molecular mechanism of trichloroethylene (TCE) cardiac developmental toxicity on zebrafish embryos and to try to provide experimental data for related intervention. Zebrafish embryos were purchased from the National Zebrafish Resource Center. The embryos were divided into DMSO(control group), DMSO+CHIR, DMSO+XAV, TCE, TCE+CHIR and TCE+XAV groups(TCE at the concentration of 1, 10 and 100 ppb, with the DMSO as control; DMSO: Dimethyl suldoxide; CHIR: CHIR-99021, Wnt agonist; XAV: XAV-939, Wnt antagonist), 60 embryos per group. Zebrafish embryos were fed in systematic aquaculture water, 28℃. The water was replaced every 24 h and drugs were added according to the grouping scheme. The cardiac tissues were dissected and analyzed by transcriptome microarray after RNA extraction. The expressions of Wnt signaling pathway related genes were verified by q-PCR. Wnt atagonist XAV and activator CHIR were used alone or in combination to further evaluate the possibility of the Wnt signaling participating in the cardiac developmental toxicity induced by TCE. Compared with control, Zebra fish embryos exposed to TCE showed a significant increase in heart defects, and the main phenotypes were abnormal atrioventricular ratio, looping defects and pericardial edema. The results of microarray profiling showed that the expressions of genes related to Wnt signaling pathway were affected significantly. The results of qPCR further confirmed that TCE inhibited the expressions of Wnt pathway target genes Axin2, Sox9b and Nkx2.5(P＜0.05). Wnt agonist CHIR reduced the TCE-induced cardiac malformation rate significantly, while the addition of Wnt antagonist XAV markedly enhanced the cardiac developmental toxicity of TCE. Exposure to TCE leads to heart malformation in zebrafish embryos. Wnt signaling pathway may be involved in the cardiac developmental toxicity induced by TCE.

Developmental Toxicity of TCE Exposure in Zebrafish: Analyzing Vitamin D Metabolism

Background and Hypothesis: Trichloroethylene (TCE) is an industrial solvent used since the 1940s. A known carcinogen, it is found in over half of Superfund sites where levels have reached 12,000 parts per billion (ppb; µg/L), though the US Environmental Protection Agency maximum contaminant level in drinking water is 5 ppb. In this study, the zebrafish model was used to investigate the developmental toxicity of TCE by assessing its effects on metabolism. Preliminary studies have shown a reduction in gene expression of the cytochrome P450 (CYP) enzymes responsible for breakdown of vitamin D. As a result, we expected to see lower levels of downstream metabolites, namely calcitriol, as detected by an Enzyme-Linked Immunosorbent Assay (ELISA). 
 Experimental Design: At 0-2 hours post fertilization (hpf), embryos were dosed with TCE at either 0 or 10 ppb. At 72 hpf, the larvae were removed from the TCE and prepared for the ELISA procedure. 
 Results: ELISA revealed similar levels of calcitriol between the control and 10 ppb groups. The difference between the two groups did not show statistical significance (p>0.05). 
 Conclusion: These results suggest that there may not be a direct relationship between CYP gene expression and certain downstream metabolic effects or that the organism was able to compensate for the biological changes. If the latter, additional time points for TCE exposure could be evaluated. As studies continue, we plan to evaluate CYP gene expression at higher concentrations to correlate with other biological effects and determine if there is consistency with results from lower concentrations.

Irreversible effects of trichloroethylene on the gut microbial community and gut-associated immune responses in autoimmune-prone mice.

The developing immune system is particularly sensitive to immunotoxicants. This study assessed trichloroethylene (TCE)-induced effects on the gut microbiome and cytokine production during the development in mice. Mice were exposed to TCE (0.05 or 500μg/mL) at the levels that approximate to environmental or occupational exposure, respectively. Mice were subjected to a continuous developmental exposure to these doses encompassing gestation, lactation and continuing directly in the drinking water postnatally for 154days (PND154) or PND259. To observe persistence of the effect TCE was removed from the drinking water in a subset of mice on PND154 and were provided regular drinking water until the study terminus (PND259). Abundance of total tissue-associated bacteria reduced only in mice exposed to TCE until PND259. The ratio of Firmicutes/Bacteroidetes did not alter during this continuos exposure; however, cessation of high-dose TCE at PND154 resulted in the increased abundance Bacteroidetes at PND259. Furthermore, high-dose TCE exposure until PND259 resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and increased abundance of genus Bifidobactrium and bacterial family Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the production of interleukin-33; that might play a dual role in maintaining the balance and homeostasis between commensal microbiota and mucosal health. At PND259, interleukin-3, granulocyte-macrophage colony-stimulating factor and Eotaxin were altered in both, the continuous exposure and cessation groups, whereas only a cessation group had a higher level of KC that may facilitate infiltration of neutrophils. The irreversible effects of TCE after a period of exposure cessation suggested a unique programming and potential toxicity of TCE even at the environmental level exposure.

Toxic effects of subacute inhalation exposure to trichloroethylene on serum lipid profile, glucose and biochemical parameters in Sprague–Dawley rats

The current study evaluated the inhalation toxicity of trichloroethylene (TCE) at 0, 10, 100, 250 and 400 ppm in Sprague–Dawley rats for 10 day period, because the subacute inhalation toxicity of TCE on serum lipid profile, glucose and some biochemical parameters has not been previously reported. TCE vapors were generated using the dynamic generation system based on evaporation method in the exposure chamber. On the basis of the results, mean serum low-density lipoprotein (LDL) and albumin (ALB) decreased significantly in all the groups exposed to TCE compared with the control group (p < .005), but there was a significant increase for parameters: fasting blood glucose (FBG) and alkaline phosphatase (ALP) (p < .005). Rats exposed to 400 ppm TCE showed a significant decrease in serum cholesterol (CHOL) and protein (Pr) compared with the control group (p < .005). A negative relationship was found between triglycerides (TG), very low density lipoprotein (VLDL), CHOL, LDL, Pr, ALB and urea levels and the subacute exposure to concentrations of TCE (R2 = –0.26, p < .05), but there was a direct correlation for parameters FBG, ALP and alanine aminotransferase (ALT) (R2 = 0.42, p < .05). In conclusion, studies with Sprague–Dawley rats demonstrated that subacute inhalation exposure to TCE (≥ 100 PPM) is associated with biochemical and lipotoxicity in the form of decreased serum ALB and LDL and raised ALP and glucose levels. The present study also provides additional evidence relating to decreased serum CHOL and Pr after subacute inhalation exposure to 400 ppm TCE.

Metabolism and Toxicity of Trichloroethylene and Tetrachloroethylene in Cytochrome P450 2E1 Knockout and Humanized Transgenic Mice.

Trichloroethylene (TCE) and tetrachloroethylene (PCE) are structurally similar olefins that can cause liver and kidney toxicity. Adverse effects of these chemicals are associated with metabolism to oxidative and glutathione conjugation moieties. It is thought that CYP2E1 is crucial to the oxidative metabolism of TCE and PCE, and may also play a role in formation of nephrotoxic metabolites; however, inter-species and inter-individual differences in contribution of CYP2E1 to metabolism and toxicity are not well understood. Therefore, the role of CYP2E1 in metabolism and toxic effects of TCE and PCE was investigated using male and female wild-type [129S1/SvlmJ], Cyp2e1(-/-), and humanized Cyp2e1 [hCYP2E1] mice. To fill in existing gaps in our knowledge, we conducted a toxicokinetic study of TCE (600 mg/kg, single dose, i.g.) and a subacute study of PCE (500 mg/kg/day, 5 days, i.g.) in 3 strains. Liver and kidney tissues were subject to profiling of oxidative and glutathione conjugation metabolites of TCE and PCE, as well as toxicity endpoints. The amounts of trichloroacetic acid formed in the liver was hCYP2E1≈ 129S1/SvlmJ > Cyp2e1(-/-) for both TCE and PCE; levels in males were about 2-fold higher than in females. Interestingly, 2- to 3-fold higher levels of conjugation metabolites were observed in TCE-treated Cyp2e1(-/-) mice. PCE induced lipid accumulation only in liver of 129S1/SvlmJ mice. In the kidney, PCE exposure resulted in acute proximal tubule injury in both sexes in all strains (hCYP2E1 ≈ 129S1/SvlmJ > Cyp2e1(-/-)). In conclusion, our results demonstrate that CYP2E1 is an important, but not exclusive actor in the oxidative metabolism and toxicity of TCE and PCE.

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.

Trichloroethylene (TCE) is a common environmental pollutant associated with adverse reproductive outcomes in humans. TCE intoxication occurs primarily through its biotransformation to bioactive metabolites, including S-(1,2-dichlorovinyl)-l-cysteine (DCVC). TCE induces oxidative stress and inflammation in the liver and kidney. Although the placenta is capable of xenobiotic metabolism and oxidative stress and inflammation in placenta have been associated with adverse pregnancy outcomes, TCE toxicity in the placenta remains poorly understood. We determined the effects of DCVC by using the human extravillous trophoblast cell line HTR-8/SVneo. Exposure to 10 and 20 μM DCVC for 10 h increased reactive oxygen species (ROS) as measured by carboxydichlorofluorescein fluorescence. Moreover, 10 and 20 μM DCVC increased mRNA expression and release of interleukin-6 (IL-6) after 24-h exposure, and these responses were inhibited by the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid and by treatments with antioxidants (alpha-tocopherol and deferoxamine), suggesting that DCVC-stimulated IL-6 release in HTR-8/SVneo cells is dependent on beta-lyase metabolic activation and increased generation of ROS. HTR-8/SVneo cells exhibited decreased mitochondrial membrane potential at 5, 10, and 20 μM DCVC at 5, 10, and 24 h, showing that DCVC induces mitochondrial dysfunction in HTR-8/Svneo cells. The present study demonstrates that DCVC stimulated ROS generation in the human placental cell line HTR-8/SVneo and provides new evidence of mechanistic linkage between DCVC-stimulated ROS and increase in proinflammatory cytokine IL-6. Because abnormal activation of cytokines can disrupt trophoblast functions necessary for placental development and successful pregnancy, follow-up investigations relating these findings to physiologic outcomes are warranted.

Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase

Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson’s disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1−/−) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1−/− mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity.