Unusual case of anxiety: trichloroethylene neurotoxicity.

I present an uncommon case of recurrent, intractable anxiety that was presented acutely and slowly evolved into a chronic debilitating condition. A young previously fit and healthy 24-year-old patient presents with somewhat atypical symptoms of anxiety. Full medical work-up including examination, blood, ECG electrocardiogram, electroencephalogram and CT of the head was unremarkable. When the history was explored in detail, it was revealed he worked in the navy and was exposed to a neurotoxic solvent, trichloroethylene. This case highlights the importance of eliciting a detailed occupational history, particularly paying attention to patient demographics such as occupation and presenting symptoms that do not readily fit into diagnostic criteria.

[An investigation to an accident of occupational trichloroethylene explosion].

Objective: To investigation to an accident of occupational trichloroethylene explosion and analyze the clinical datas. Methods: An investigation was carried out on the explosion of trichloroethylene in a place in shandong province in June 2016, and the clinical data of 4 patients with trichloroethylene poisoning were analyzed. Results: The incident is caused by irregularities in workers, 4 patients were characterized by different levels of the respiratory system, nervous system, liver, and skin lesions. Among them, respiratory system damage was more prominent, mainly manifested as chemical bronchitis and pneumonia, after positive rescue and treatment all recovered and discharged. Conclusions: Trichloroethylene leak can cause severe ex-plosion accidents, can cause workers of the respiratory system, nervous system, liver and skin lesions, mainly glucocorticoids comprehensive therapy has good curative effect.

Medico legal investigations into sudden sniffing deaths linked with trichloroethylene.

Sudden deaths attributed to sniffing trichloroethylene are caused by the abuse of this solvent which produces pleasant inebriating effects with rapid dissipation. In the event of repeated cycles of inhalation, a dangerous and uncontrolled systemic accumulation of trichloroethylene may occur, followed by central nervous system depression, coma and lethal cardiorespiratory arrest. Sometimes death occurs outside the hospital environment, without medical intervention or witnesses and without specific necroscopic signs. Medico legal investigations into sudden sniffing deaths associated with trichloroethylene demand careful analysis of the death scene and related circumstances, a detailed understanding of the deceased's medical history and background of substance abuse and an accurate evaluation of all autopsy and laboratory data, with close cooperation between the judiciary, coroners and toxicologists.

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

Occupational trichloroethylene hypersensitivity syndrome: human herpesvirus 6 reactivation and rash phenotypes.

BACKGROUND: Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational TCE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). OBJECTIVE: This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. METHODS: HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. RESULTS: The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (≥100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p<0.01). Positive correlations between HHV6 DNA, TNF-α, IFN-γ, IL-6 and IL-10 were significant (p<0.05) except for that between HHV6 DNA and IFN-γ. An increase in HHV6 DNA was positively associated with an increase in TNF-α on admission (p<0.01). HHV6 DNA, the antibody titers, TNF-α and IL-10 concentrations were significantly higher in ED than in the non-ED type (p<0.05). CONCLUSION: Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash.

Assessment of serum S100B and neuron specific enolase levels to evaluate the neurotoxic effects of organic solvent exposure.

OBJECTIVES: Long-term organic solvent exposure may cause toxic effects in central nervous system . Trichloroethylene (TCE) is known to be one of the neurotoxic chlorinated organic solvents. Trichloroacetic acid (TCA) is an oxidative pathway metabolite of TCE. S100B, a calcium-binding protein in glial cells, and neuron specific enolase (NSE) in neuron cytoplasma are protein markers of astrocyte and neuron damage, respectively. MATERIALS AND METHODS: Clinical and laboratory assesments were performed in 25 participants with organic solvent exposure history. Control group included 25 healthy age and sex-matched individuals. Measurements of serum S100B and NSE were performed using Roche Cobas E 601 compatible kits and elechtrochemiluminescence immunoassay. The levels of TCA in urine were measured by the headspace GC technique, after methyl esterification by methanol. RESULTS: Median value of urine TCA in solvent-exposed group was 12.30 mg/L with 10.20 mg/L and 35.00 mg/L minimum and maximum values, respectively. The difference between serum S100B levels of solvent-exposed group (0.064 µg/L) and control group (0.049 µg/L) was statistically significant (p < 0.05). Serum NSE levels of control group (15.61 ng/ml) were higher than solvent-exposed group (13.90 ng/ml) but difference was not statistically significant (p > 0.05). CONCLUSIONS: Serum S100B levels were found to be higher in solvent-exposed group when compared with control group. NSE levels were comparable between two groups. Increased Serum S100B levels in organic solvent exposure may indicate a preventive response to neuronal damage caused by reactive oxygen species (ROS) produced through oxidative metabolic pathways of organic solvents.

Risk of cancer among workers exposed to trichloroethylene: analysis of three Nordic cohort studies.

BACKGROUND: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. METHODS: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. RESULTS: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. CONCLUSIONS: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Solvents and Parkinson disease: a systematic review of toxicological and epidemiological evidence.

Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia nigra. The causes of PD remain poorly understood, although environmental toxicants may play etiologic roles. Solvents are widespread neurotoxicants present in the workplace and ambient environment. Case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE). Animal toxicology studies have been conducted on various organic solvents, with some, including TCE, demonstrating potential for inducing nigral system damage. However, a confirmed animal model of solvent-induced PD has not been developed. Numerous epidemiologic studies have investigated potential links between solvents and PD, yielding mostly null or weak associations. An exception is a recent study of twins indicating possible etiologic relations with TCE and other chlorinated solvents, although findings were based on small numbers, and dose-response gradients were not observed. At present, there is no consistent evidence from either the toxicological or epidemiologic perspective that any specific solvent or class of solvents is a cause of PD. Future toxicological research that addresses mechanisms of nigral damage from TCE and its metabolites, with exposure routes and doses relevant to human exposures, is recommended. Improvements in epidemiologic research, especially with regard to quantitative characterization of long-term exposures to specific solvents, are needed to advance scientific knowledge on this topic.

[Analysis on the occupational poisoning case of trichloroethylene reported in Dongguan during 2002 to 2009 ].

OBJECTIVE: To understand the demographic, occupational and clinic characteristics of occupational poisoning case due to trichloroethylene in Dongguan in recent years for the purpose of prevention. METHODS: Using the trichloroethylene patients of poisoning diagnosed in the years between 2002 to 2009 as subjects, their age, sex, industry, job, working duration and exposure level were analysed. RESULTS: In Dongguan between 2002 and 2009 altogether 82 cases were reported, among the 82 cases 8 patients were dead with case fatality rate of 9.8%. among them there were 12 cases of poisonings(8 females ,4 males); 9 cases were classified as mild poisonings and the rest serious ones, among the 12 cases 3 patients were dead with case fatality rate of 25.0%; Dermatitis caused by TCE there were 70 cases (37 males and 33 females), among the 70 cases 5 patients were dead with case fatality rate of 7.1%. 11 persons (91.7%) were engaged in the job of cleaning and 1 (8.3%) in water gun, and they performed the job only for 3 days in shortest and for 450 days in longest. The cases were distributed in the jobs as the following: 29 (41.4%), 12 (17.1%), 8 (11.4%), 5 (7.1%), 4 (5.7%), cases respectively in the job of cleaning, parts hanging, board washing, painting, gun water spraying; a job duration of 1-50 d (27.4 days in average). CONCLUSION: In summary the TCE poisonings in Dongguan were two types of poisoning, i.e., systematic poisonings and drug rash-like dermatitis, occupational TCE poisonings took place mainly in the cleaning workers. Dermatitis caused by TCE can cure but hard to prevent, we should strengthen the early examination of new works.

Occupational trichloroethylene exposure and renal carcinoma risk: evidence of genetic susceptibility by reductive metabolism gene variants.

Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.

Clinical analysis of seven cases of trichloroethylene medicamentose-like dermatitis.

To grasp the clinical characteristics, treatment and prognosis of trichloroethylene medicamentose-like dermatitis, seven hospitalized cases were analyzed in detail. The disease has various manifestations, among them, those accompanied by hepatitis or renal diseases are crucial. Adequate dose of corticosteroid hormone in earlier period could effectively control the patient's condition. Besides paying close attention to changes of the patient's skin, we should also keep an eye for the changes of the liver and kidneys and their relevant indices, as different patients have different prognoses.

A rare cause of abdominal compartment syndrome: acute trichlorethylene overdose.

INTRODUCTION: The clinical signs of acute trichlorethylene overdose are commonly coma, cardiac conduction disturbances, diarrhea, and vomiting. We report a case of intentional massive trichlorethylene ingestion inducing a fatal abdominal compartment syndrome (ACS). CASE REPORT: A 47-year-old woman was admitted to the emergency department after intentionally ingesting 500 mL of trichlorethylene and benzodiazepines. She rapidly developed coma and abdominal distension leading to multiple organ failure. Subsequent surgical evaluation revealed abdominal perforation and necrosis, and life-sustaining treatments were therefore withdrawn. DISCUSSION: This is a primary ACS that can be explained from experimental data on the pathophysiology of pneumatosis cystoides coli. For this case, we discuss multiple etiological factors for intra-abdominal hypertension (IAP), such as paralytic ileus and massive fluid resuscitation due to the direct toxicity of ingested trichlorethylene. CONCLUSION: Patients ingesting trichlorethylene need to be closely evaluated for risk of digestive damage and perforation. Early prompt laparotomy must be performed in cases of ACS.