Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Gist, Ginger L.; Burg, JeAnne R.

doi:10.1177/074823379501100301

Cited by 64 publications

(48 citation statements)

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“…In vitro studies suggested that CYP2E1 is the principal high-affinity enzyme responsible for TCE metabolism. The objective of the present work is to more directly assess the role of CYP2E1 in the metabolism and disposition of 1,2-14 C-TCE administered at 250 or 1000 mg/kg (gavage) using Trichloroethylene (TCE) is a nonflammable solvent that is used as a metal degreasing agent and an ingredient in the manufacturing of glue, paint, and spot removers (Davidson and Beliles, 1991;Gist and Burg, 1995). TCE is a common contaminant of ground and surface water as well as soil and air (Westirck et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Kim¹,

Ghanayem²

2006

Drug Metab Dispos

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ABSTRACT:Trichloroethylene (TCE)1 is an important environmental contaminant, a well established rodent carcinogen, and a "probable human carcinogen". Metabolism of TCE occurs primarily via cytochrome P450 (P450)-dependent oxidation. In vitro studies suggested that CYP2E1 is the principal high-affinity enzyme responsible for TCE metabolism. The objective of the present work is to more directly assess the role of CYP2E1 in the metabolism and disposition of 1,2-14 C-TCE administered at 250 or 1000 mg/kg (gavage) using Trichloroethylene (TCE) is a nonflammable solvent that is used as a metal degreasing agent and an ingredient in the manufacturing of glue, paint, and spot removers (Davidson and Beliles, 1991;Gist and Burg, 1995). TCE is a common contaminant of ground and surface water as well as soil and air (Westirck et al., 1984). Owing to its volatility and lipophilicity, TCE is readily absorbed through the lungs and gastrointestinal tract and distributed to various tissues. Exposure to TCE causes a variety of tumors depending on species and tissues (Green, 2000;Clewell and Andersen, 2004). In mice, TCE causes lung and liver tumors after inhalation or gavage exposure (Rhomberg, 2000). Furthermore, exposure to TCE induces kidney and lung toxicity, and inhibits male fertility (Green et al., 1997;DuTeaux et al., 2004;Forkert et al., 2006). Human exposure to TCE was associated with elevated risks of tumors at numerous sites (Raaschou-Nielsen et al., 2002), and was classified as a "probable human carcinogen" (IARC, 1995; NTP, 2002).TCE metabolism occurs via conjugation with glutathione via glutathione S-transferase and oxidation via the cytochrome P450 (P450) enzymes (Lash et al., 2000). glutathione S-transferase-dependent conjugation of TCE is a minor pathway and occurs in the liver and kidney. Subsequent metabolism via the ␤-lyase enzyme leads to the conversion of S-(1,2-dichlorovinyl)-L-cysteine to S-1,2-dichlorovinyl thiol, which is implicated in TCE-induced nephrotoxicity in rats (Elfarra et al., 1986;Lash et al., 2001). Although TCE conjugation is distinguishable from its oxidation in terms of the metabolites produced and target organ specificity, this pathway is not considered quantitatively significant. However, at elevated exposure levels of TCE when the high-affinity oxidative pathway is saturated, the role of conjugation may become more significant (Lash et al., 1998).P450-dependent oxidative metabolism of TCE occurs primarily in the liver and in other organs, such as lung, kidney, and reproductive tract. Although different isozymes (CYP1A1/2, CYP2B1/2, CYP2C11/6, and CYP2E1) have been identified as playing a role in TCE metabolism (Nakajima et al., 1993), CYP2E1 is regarded as a major high-affinity isozyme in the oxidation of TCE. Recent reports showed that CYP2E1, CYP2F, and CYP2B1 are the main enzymes involved in the pulmonary bioactivation of TCE (Forkert et al., 2005(Forkert et al., , 2006. The initial proposed step in the oxidation of this chemical is the conversion to TCE epoxide ( Fig. 1), which may ...

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Section: Introductionmentioning

confidence: 99%

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Kim¹,

Ghanayem²

2006

Drug Metab Dispos

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“…Human TCE exposure (both occupational and environmental) has been linked to several autoimmune diseases (scleroderma, systemic lupus erythematosus, hepatitis and diabetes [3][4][5][6][7][8][9][10][11]) and hypersensitivity disorders [12][13][14]. By using a female MRL+/+ mouse model, we have shown that chronic exposure to TCE during adulthood promotes autoimmune hepatitis that corresponds to idiopathic autoimmune hepatitis in humans, that is, T-cell infiltration of the liver and development of antibodies specific for liver microsomal proteins [15,16].…”

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Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4 ⁺ T cells

et al. 2016

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Aim: Autoimmune disease and CD4+ T-cell alterations are induced in mice exposed to the water pollutant trichloroethylene (TCE). We examined here whether TCE altered gene-specific DNA methylation in CD4 + T cells as a possible mechanism of immunotoxicity. Materials & methods: Naive and effector/memory CD4 + T cells from mice exposed to TCE (0.5 mg/ml in drinking water) for 40 weeks were examined by bisulfite next-generation DNA sequencing. Results: A probabilistic model calculated from multiple genes showed that TCE decreased methylation control in CD4 + T cells. Data from individual genes fitted to a quadratic regression model showed that TCE increased gene-specific methylation variance in both CD4 subsets. Conclusion: TCE increased epigenetic drift of specific CpG sites in CD4 + T cells.

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“…The resu showed that UTCA was si ity correlted to serum insulin levls. Insulin (1) indicated that exposure to TCE in excess of national norms can cause ill effects induding speech and hearing impairments, effects of stroke, liver problems, anemia and other blood disorders, diabetes, kidney disease, urinary tract disorders, and skin rashes. However, relatively few studies have evaluated the long-term effects of exposure to TCE at levels below the threshold limit value (TLV) (2-6).…”

mentioning

confidence: 99%

Effects of Chronic Exposure to Low Doses of Trichloroethylene on Steroid Hormone and Insulin Levels in Normal Men

Goh¹,

Chia²,

Ong³

1998

Environmental Health Perspectives

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The aim ofdis studywas to exmine the senum leves ofinsulin and some adrena steroid hormones in men c expbosd toXlow doe of tricooety e (TCE). A tiotal of 85 workers participated in tis study Each worker had urine collected and analyze for trichioroacetic adds (UTCA) on the same day that a blood sample was taken for analyses of serum rone, hormOnebinding globulin (SHBG), androstenedione, cortisol, d rone, and insulin. lle mean concentraion of e UTCA was 22.4 pmg a creanTnine (rnge 0.8-136.4 (1) indicated that exposure to TCE in excess of national norms can cause ill effects induding speech and hearing impairments, effects of stroke, liver problems, anemia and other blood disorders, diabetes, kidney disease, urinary tract disorders, and skin rashes. However, relatively few studies have evaluated the long-term effects of exposure to TCE at levels below the threshold limit value (TLV) (2-6).In two early publications, we showed that long-term exposure to TCE at levels below the TLV was not associated with any significant changes in levels of reproductive hormone or spermatogenesis and semen quality (7,8). In this paper, we present the effects of long-term exposure to TCE on insulin and adrenal hormones and discuss their associations with sex hormone-binding globulin (SHBG) and testsosterone (T) levels. Materials and MethodsDetails of recruitment and profiles of subjects involved in the study, as well as the experimental design, were reported earlier (8). The study population consisted of 85 male workers of Chinese descent who worked in an electronic fictory where TCE was used as a degreaser to dean small metal parts. Informed consent was obtained from each subject.In all 85 subjects ranging from 22 to 39 years of age, there were no factors in their medical histories that would influence the endocrine functions, e.g., no history of diabetes mellitus, long-term medication, or testicular injury. No abnormalities were detected clinically. All subjects had normal liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, gamma glutamyl transpeptidase, and alkaline phosphatase).Blood colection and hormonal assay. A single venous blood sample was collected between 7:30 and 8:00 A.M. from each subject throughout the study to reduce the diurnal variation of the hormonal levels.Sera were separated and stored at -700C until assayed.Serum concentrations of testosterone, androstenedione (A4), cortisol, aldosterone, insulin, and SHBG were measured by established immunoassays. Testosterone and cortisol were measured using the World Health Organization (WHO) matched reagents and methods (9). The intra-and interassay coefficients of variation of the assays were less than 10% over the effective concentration ranges.Serum levels of SHBG and aldosterone were measured using radioimmunoassay kits purchased from DPC Inc. (Los Angeles, CA). The intra-and interassay coefficients of variation were less than 15%. Serum insulin levels were measured using kits from CIS Bio International (Yvette, Cedex,...

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Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Cited by 64 publications

References 359 publications

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4 ⁺ T cells

Effects of Chronic Exposure to Low Doses of Trichloroethylene on Steroid Hormone and Insulin Levels in Normal Men

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Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Cited by 64 publications

References 359 publications

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Comparative Metabolism and Disposition of Trichloroethylene in Cyp2e1–/–and Wild-Type Mice

Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4 + T cells

Effects of Chronic Exposure to Low Doses of Trichloroethylene on Steroid Hormone and Insulin Levels in Normal Men

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Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4 ⁺ T cells