China ; epidemiology ; Hexanes ; toxicity ; Humans ; Occupational Diseases ; epidemiology ; Trichloroethylene ; toxicity

Trichloroethylene (TCE) is a widely used organic solvent and an important industrial material. Due to mass production and use, and improper waste disposal, TCE has become a common environmental contaminant, so there is a wide range of occupationally and environmentally exposed population. Occupational and environmental exposure to TCE can produce toxic effects on multiple organs and systems. This paper is a review of the immunotoxicity, reproductive toxicity, neurotoxicity, teratogenic effect and other non-carcinogenic toxic effects of TCE from the aspects of epidemiological study, experimental evidence on animals and toxic mechanisms.
Animals ; Environmental Exposure ; Humans ; Occupational Exposure ; Solvents ; toxicity ; Trichloroethylene ; toxicity

Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.
Dermatitis, Occupational/*etiology ; Fatal Outcome ; Humans ; Hypersensitivity/*etiology ; Male ; Middle Aged ; Occupational Exposure/*adverse effects ; Solvents/*toxicity ; Trichloroethylene/*toxicity

OBJECTIVESTo study the contact allergenic activities of trichloroethylene (TCE) and its three metabolites trichloroacetic acid, trichloroethanol and chloral hydrate.

METHODSA modified guinea pig maximization test (GPMT) was adopted. The skin sensitization (edema and erythema) was observed in trichloroethylene, trichloroacetic acid, trichloroethanol, chloral hydrate and 2,4-dinitrochlorobenzene.

RESULTSThe allergenic rate of TCE, trichloroacetic acid and 2,4-dinitrochlorobenzene was 71.4%, 58.3% and 100.0% respectively, and that of trichloroethanol and chloral hydrate was 0%. The mean response score of TCE, trichloroacetic acid and 2,4-dinitrochlorobenzene was 2.3, 1.1, 6.0 respectively. The histopathological analysis also showed an induction of allergenic transformation in guinea pig skin by both TCE and trichloroacetic acid.

CONCLUSIONTCE appears to be a strong allergen while trichloroacetic acid a moderate one. On the other hand, both trichloroethanol and chloral hydrate are weak sensitization potentials. Immunologic reaction induced by TCE might be postulated as the pathological process of this illness. Consequently, it is suggested that in the mechanism of Occupational Dermatitis Medicamentose-Like (ODML) induced by TCE, the chemical itself might be the main cause of allergy. As one of its metabolic products, trichloroacetic acid might be a subordinate factor.

Allergens ; toxicity ; Animals ; Chloral Hydrate ; toxicity ; Dermatitis, Allergic Contact ; etiology ; immunology ; Dermatitis, Irritant ; etiology ; immunology ; Ethylene Chlorohydrin ; analogs & derivatives ; toxicity ; Guinea Pigs ; Skin ; drug effects ; immunology ; Toxicity Tests ; Trichloroacetic Acid ; toxicity ; Trichloroethylene ; metabolism ; toxicity

OBJECTIVETo observe the change of caspase-8, caspase-9 activity and apoptosis rates in the process of trichloroethylene-induced damage in keratinocytes, and explore the tentative mechanism of apoptosis.

METHODSHuman keratinocytes were exposed to 0.125, 0.250, 0.500, 1.000 and 2.000 mmol/L trichloroethylene for 4, 8, 12 and 24 h. The inhibitive groups were pretreated with 100 micromol/L Z-LEHD-FMK (a specific inhibitor of caspase-9) for 1 h, and were stimulated with 2.000 mmol/l TCE for 12 h. MTT assay was used to detect the viability of different cells; The activity of caspase were calculated according to spectrophotometry; Change of the apoptotic rates was assessed by flow cytometer (FCM) after double-stained with Annexin V-FITC and propidium iodide (PI).

RESULTS(1) The minimum effective concentration for cell viability reduction was 0.125 mmol/L at 12 h and the shortest time required to produce a change was 4 h at a concentration of 2.000 mmol/L (compared with control group, P < 0.01). Cell viability in all the groups markedly decreased from 12 h to 24 h (P < 0.05). (2) The activity of caspase-8 in the various dosage groups at different times had no statistical difference compared with the control group, P > 0.01. (3) At 8 h, 1.000 and 2.000 mmol/L TCE groups could significantly enhance caspase-9 activity (P < 0.05). The caspase-9 activity in all the groups showed differences and was significantly higher than those of control cells when time was over 12 h (P < 0.05). (4) After exposing to different dosages of TCE for 12 h, the rate of apoptosis rose to (80.43 +/- 4.21)% with the increase of dosage, compared with the control group, (9.40 +/- 2.98)%, which showed a dose-effect relationship. (5) The cells pre-treated with caspase-9 inhibitor resulted in a decrease in the caspase-9 activity and apoptosis rates (compared with 2.000 mmol/L TCE exposed group, P < 0.01). However, there was no statistical significance in comparison with the control group (P > 0.05).

CONCLUSIONCaspase-9 may be an important mediator of apoptosis in keratinocytes induced by trichloroethylene.

Apoptosis ; drug effects ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Humans ; Keratinocytes ; drug effects ; enzymology ; pathology ; Trichloroethylene ; toxicity

OBJECTIVETo establish the association between genetic polymorphisms of HLA-DMA and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like dermatitis (TIMLD).

METHODSSixty-one cases were medically confirmed to have been affected with TIMLD and 60 controls were selected from exposed workers who were free from TIMLD. The TIMLD cases and controls were similar in terms of age, sex, and duration of exposure. DNA was extracted both from the TIMLD cases and controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the alleles and genotypes were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB variants were compared between the two groups.

RESULTSThe results showed that the frequency of HLA-DMA*0101 and HLA-DMB*0103 alleles was significantly increased in TIMLD patients than in controls (71.3% vs. 55.0% for HLA-DMA*0101; P<0.05) (11.5% vs. 3.3% for HLA-DMB*0103; P<0.05). In addition, the frequency of HLA-DMA*0102-*0102 homozygous genotype was also significantly higher in the controls than in the patients (25.0% vs. 8.2%, P<0.05), whereas the frequency of heterozygous HLA-DMB *0101-*0102 genotype was lower in the patients in comparison with the controls. Conclusion The polymorphisms of HLA-DM may be associated with the susceptibility to TIMLD.

Alleles ; Dermatitis, Contact ; genetics ; Genetic Predisposition to Disease ; HLA-D Antigens ; genetics ; Humans ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Trichloroethylene ; toxicity

Animals ; DNA Damage ; Dose-Response Relationship, Drug ; Isotope Labeling ; Male ; Phosphorus Radioisotopes ; analysis ; Rats ; Rats, Sprague-Dawley ; Trichloroethylene ; toxicity

OBJECTIVETo explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.

METHODSThe blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.

RESULTSC3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).

CONCLUSIONThe type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.

Adolescent ; Adult ; Complement System Proteins ; immunology ; Dermatitis, Occupational ; immunology ; Female ; Humans ; Male ; Occupational Exposure ; Trichloroethylene ; toxicity ; Young Adult

OBJECTIVETo study the changes of serum complement C and immunoglobulin (Ig) in sensitized guinea pigs exposed to trichloroethylene.

METHODSThirty six white female guinea pigs (250 ∼ 300 g) were randomly divided into blank control group (5 guinea pig), solvent (olive oil) control group (5 guinea pig) and TCE treatment group (26 guinea pig). According to guinea pig maximization test (GPMT), guinea pigs were exposed to TCE. After stimulating contact for 24 h, the skin reactions of guinea pig back test area were recorded and scored. According to Skin sensitization integral, the guinea pigs treated with TCE were divided into the sensitized group (score ≥ 1) and un-sensitized group (score 0). The concentrations of serum C3, C4, IgA, IgG and IgM were detected in 24 and 72 h, respectively after the experiment.

RESULTSThe sensitization rates of group treated by TCE was 65.38%. The serum C3 levels of groups sensitized to TCE for 24 and 73h were 99.75 ± 1.45 and 93.28 ± 3.61g/ml, respectively, which were significantly lower than that (112.30 ± 9.10 g/ml) of solvent control group (P < 0.05). Also The serum C4 levels of groups sensitized to TCE for 24 and 73 h were 34.63 ± 2.53 and 33.82 ± 2.76g/ml, respectively, which were significantly lower than that (43.87 ± 3.65 g/ml) of solvent control group (P < 0.05). The serum IgA and IgM levels of groups sensitized to TCE and unsensitized to TCE for 24 and 72 h were significantly lower than those of solvent group (P < 0.05). as compared with unsensitized groups, the serum IgA levels of the groups sensitized to TCE for 24 and 72 h significantly decreased (P < 0.05).

CONCLUSIONAfter the guinea pig skin was sensitized to TCE, the serum C3, C4 levels decreased, the immune function disordered.

Animals ; Complement System Proteins ; metabolism ; Female ; Guinea Pigs ; Immunity, Humoral ; drug effects ; Immunoglobulins ; blood ; Skin ; drug effects ; Trichloroethylene ; toxicity

OBJECTIVETo explore the effects of trichloroethylene (TCE) on cardiac developmental differentiation in human embryonic stem cells.

METHODSIn this study, based on the human embryonic stem cells in vitro cardiac differentiation assay, we investigated the potential effect of TCE exposure on the cardiac toxicity in embryo development. Human embryonic stem cells were treated with TCE at different concentrations of 100 ppb, 1 ppm, and 10 ppm and dimethyl sulfoxide(DMSO) treated as control. The MTT assay was performed to examine the cytoplasmic toxicity of TCE exposure. The beating percentages were recorded and the expression of cardiac specific gene was evaluated by PCR or flow cytometry. Also, real time PCR was performed to verify the micro array analysis on the expression level changes of genes which were involved in the Ca2+ signal pathways.

RESULTSCompared with the control group, there was no significant difference in cell viability when cells were treated with TCE at the concentrations of 100 ppb, 1 ppm, and 10 ppm. However, TCE could inhibit the expression of cTnT protein in a concentration-dependant manner. And the most interestingly, TCE significantly inhibited the cardiac differentiation characterized by the decrease beating percentages. Genes involved in Ca2+ signaling pathway were severely disrupted by TCE.

CONCLUSIONTCE inhibited the cardiac specific differentiation of human embryonic stem cell and at the meanwhile the genes responsible for Ca2+ signaling pathway were severely disrupted, which could contribute the severe effects of TCE cardiotoxicity.

Calcium Signaling ; Cell Differentiation ; Cells, Cultured ; Embryonic Development ; Embryonic Stem Cells ; cytology ; drug effects ; Heart ; embryology ; Humans ; Trichloroethylene ; toxicity