Lesiones oculares provocadas por el gas mostaza (sulfuro de dicloroetilo) durante la I Guerra Mundial: clínica, terapéutica y secuelas / Eye injuries caused by mustard gas (dichloroethyl sulphide) during the 1st World War: clinical, therapeutica and sequelae

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[Evaluation of professional exposure to chloride vinyl monomer and vinyl idene chloride for a pharmaceutical packaging worker]. / Valutazione dell'esposizione professionale a cloruro di vinile monomero e cloruro di vinilidene di un lavoratore addetto al confezionamento farmaci.

The study was conducted by Judicial Policy investigations of Prosecution's Office. The event was connected by a professional founded suspicion disease of a pharmaceutical worker. First information coming from the Authority indicated a chloride vinyl monomer (CVM) exposure. We applied a chemical risk assessment method to estimate real professional exposure. The method was based on the productive cycle, physical and chemical and toxicological properties. The method combined to environmental data permitted to formulate etiological hypothesis. The worker during drugs packaging was exposed to CVM and vinylidene chloride (CVDM) caused by blister warming and by glue deposition. We explain the evaluations by which we could consider the pollutant different distribution in workplaces.

Analysis of a cluster of cases of Wegener granulomatosis.

BACKGROUND: Wegener granulomatosis is a chronic inflammatory autoimmune disease of unknown etiology. The sporadic occurrence, lack of familial or genetic associations, and rising incidence suggest possible exposure to environmental agents as causative for this disease. OBJECTIVE: The objective of this study was to examine possible environmental triggers of Wegener granulomatosis. METHODS: While conducting an environmental survey of potential precipitants of Wegener granulomatosis on a cohort of patients seen at Doylestown Hospital and at the University of Pennsylvania, we identified a cluster of cases in the Dublin, Pennsylvania, region. Through hospital records and patient contacts, we located 7 cases diagnosed in a 3-year period within a 10-mile radius of an Environmental Protection Agency (EPA) Superfund toxic waste site. The radius of inclusion represents a population of approximately 50,000 individuals. Assuming complete ascertainment of cases--which is unlikely given the methods used to acquire patients--the prevalence is 2- to 4-fold greater than the expected rate of 3 per 100,000. We identified toxins at or above "action level" within the demarcated geographic region using published data from the EPA. Furthermore, we queried patients regarding their particular chemical exposures. RESULTS: These patients with Wegener granulomatosis were possibly exposed to high levels of trichloroethylene (TCE), vinyl chloride, methyl tertiary-butyl ether (MTBE), dichloroethene (DCE), and chromic acid from several industrial waste sites within the area. Additionally, these patients reported a total of greater than 30 possible exposures, including the aforesaid chemical contaminants. Three of 5 patients whose water source is known had well water that exposed them to industrial runoff and necessitated EPA intervention. CONCLUSION: This data, along with other epidemiologic studies, suggest possible toxic exposures as potentially correctable risk factors for Wegener granulomatosis. We encourage clinicians to seek data that suggests an unusual environmental exposure and to solicit information that might implicate an industrial source for these exposures.

Solvents and vapor intrusion pathways.

Vapor intrusion must be recognized appropriately as a separate pathway of contamination. Although many issues resemble those of other forms of contamination (particularly its entryway, which is similar to that of radon seepage), vapor intrusion stands apart as a unique risk requiring case-specific action. This article addresses these issues and the current understanding of the most appropriate and successful remedial actions.

Cardiac teratogenicity of trichloroethylene metabolites.

OBJECTIVES: The hypothesis of this study was that metabolites of trichloroethylene (TCE), dichloroethylene (DCE) and related compounds were responsible for fetal cardiac teratogenic effects seen when TCE or DCE is consumed by pregnant rats during organogenesis. Identification of teratogenic metabolites would allow more accurate assessment of environmental contaminants and public health risks from contaminated water or possibly municipal water supplies which, when chlorinated, may produce these potentially dangerous chemicals. BACKGROUND: Human epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have shown an increased incidence of congenital cardiac lesions in animals exposed to TCE and DCE. METHODS: Metabolites and compounds studied in drinking water exposure included: trichloroacetic acid (TCAA), monochloroacetic acid (MCAA), trichloroethanol (TCEth), carboxy methylcystine (CMC), trichloroacetaldehyde (TCAld), dichloroacetaldehyde (DCAld), and dichlorovinyl cystine (DCVC). Compounds were administered to pregnant rats during fetal heart development. RESULTS: Fetuses of rats receiving 2,730 ppm TCAA in drinking water were the only group that demonstrated a significant increase in cardiac defects (10.53%) compared with controls (2.15%) on a per fetus basis (p = 0.0001, Fischer's exact test), and a per litter basis (p = 0.0004, Wilcoxon and p = 0.0015, exact permutation tests). Trichloroacetic acid also demonstrated an increased number of implantation and resorption sites (p < 0.05) over controls. Other maternal and fetal variables showed no statistically significant differences between treated and untreated groups. CONCLUSIONS: Of the metabolites tested, only TCAA appeared to be a specific cardiac teratogen in the fetus when imbibed by the maternal rat.

1,1-Dichloroethylene-induced alterations in glutathione and covalent binding in murine lung: morphological, histochemical, and biochemical studies.

Non-ciliated Clara cells of the pulmonary bronchiolar epithelium are preferentially damaged by administration of 1,1-dichloroethylene (1,1-DCE) to mice. In this study, an in vivo system was utilized to investigate the dose-dependent effects of 1,1-DCE (75, 125, 175, and 225 mg/kg) on covalent binding and on reduced glutathione (GSH) in murine lung. Treatment of mice with each dose level of 1,1-DCE elicited significant decreases in GSH content and resulted in covalent binding of [14C]1,1-DCE in a dose-dependent manner. Histochemical staining for GSH in lungs of control mice revealed positive cellular sites in alveolar septa and bronchiolar epithelium, with the highest staining intensities in Clara cells. Staining was reduced after exposure to 75 and 125 mg/kg 1,1-DCE, and at higher doses it was abolished in alveolar septa and retained in bronchiolar epithelium, albeit at considerably reduced intensities. Heterogeneity with respect to staining intensities was consistently observed in the Clara cell population in both control and 1,1-DCE-treated mice. Progressive increases in covalent binding and decreases in GSH content correlated with increasing severities of Clara cell injury. These results show a dose dependence in regard to the magnitudes of [14C]1,1-DCE binding, the alterations in cellular GSH, and the severities of Clara cell necrosis.

The differential effects of hepatotoxicants on the sulfation pathway in rats.

This study characterized the effects of liver damage produced by a variety of hepatotoxicants on several components of the sulfation pathway in rats. Specifically, the concentration of cosubstrate, adenosine 3'-phosphate 5'-phosphosulfate (PAPS), and the hepatic capacity for PAPS synthesis were measured in livers of rats treated with carbon tetrachloride (CCl4), 1,1-dichloroethylene (DCE), alpha-naphthylisothiocyanate (ANIT), aflatoxin B1 (ATX), allyl alcohol (AA), bromobenzene (BB), cadmium chloride (Cd), or thioacetamide (TA). Liver damage was assessed by measuring serum sorbitol dehydrogenase (SDH) and alanine aminotransferase (ALT) activities as well as by histopathological examination. Hepatic PAPS concentration was generally decreased as a result of treatment with hepatotoxicants (35-80% of control), although BB, AA, and ANIT were without effect. Maximal hepatic capacity for PAPS synthesis, determined as the activities of PAPS synthetic enzymes, ATP sulfurylase, and APS kinase, was selectively decreased by the hepatotoxicants. ATP sulfurylase activity was decreased by Cd and TA (55 and 62% of control, respectively), whereas APS kinase activity was decreased by Cd, TA, BB, and DCE (60-77% of control, respectively). In addition, phenol sulfotransferase (PST) activity was measured toward 1- and 2-naphthol in order to determine whether apparent changes in PST activity in damaged livers are substrate-dependent. Treatment with hepatotoxicants generally decreased 1-naphthol-directed PST activity but not PST activity directed toward 2-naphthol. In conclusion, (1) not all xenobiotic-induced liver injury results in decreased hepatic PAPS concentration, (2) some hepatotoxicants decrease PAPS concentration by a mechanism other than decreased cosubstrate synthesis, and (3) the effect of hepatotoxicants on PST activity is dependent upon the choice of substrate used in the enzymatic assay.

Factors for efficiency of the Salmonella/microsome mutagenicity assay.

Factors were studied which modify the enzymatic capacity of mouse liver microsomal mixed-function oxidase to convert vinylidene chloride (1.1-dichloroethylene) (VDC) into mutagens in the Salmonella/microsome mutagenicity test. A microsomal fraction incorporated in soft agar layer converted VDC into mutagens during 7 h at a constant rate; these were detected with S. typhimurium TA100. In absence of VDC the enzymatic activity declined gradually to nil after 14 h of incubation at 37 degrees C. The presence of EDTA greatly enhanced the microsome-mediated mutagenicity of VDC and led to prolonged enzymatic viability, but only when liver fractions from phenobarbitone (PB) pretreated mice were used. The efficiency of the plate incorporation assay for the detection of mutagens is discussed in comparison with assays in liquid suspension.

A health study of employees exposed to vinylidene chloride.

Previous studies have reported on employee populations exposed coincidentally to vinylidene chloride in copolymer processes using vinyl chloride. The current study examines the mortality and health examination findings of 138 employees exposed to measured levels of vinylidene chloride where vinyl chloride was not used as a copolymer. There were no findings statistically related or individually attributable to vinylidene chloride exposure in this employee population. It is recommended that additional epidemiological studies be undertaken to develop data on chronic exposure to vinylidene chloride.

Mutagenicity of volatile anesthetics: halothane.

The mutagenicity of halothane was tested in an in-vitro microbial assay system employing two histidine-dependent mutants of Salmonella typhimurium, TA98 and TA100, Halothane in concentrations ranging from 0.1 to 30 per cent was incubated with bacteria in the presence or absence of a metabolic activation system prepared from either rat liver treated with Aroclor 1254 or human liver. Trifluoroacetic acid, a major metabolite of halothane, and urine from patients anesthetized with halothane also were tested. Halothane, trifluoroacetic acid, and patients' urines were not mutagenic.