Reactive airways dysfunction syndrome following exposure to a fluorocarbon.
This report describes the case of a 43-yr-old male who developed reactive airways dysfunction syndrome after exposure to a high level of bromotrifluoromethane (CF3Br, Halon 1301), a fluorocarbon widely used in automatic fire extinguishing systems. The patient was a previously healthy, nonatopic male, who developed wheezing and intermittent and reversible obstructive ventilatory impairment starting immediately after a large accidental nonfire-related release of CF3Br in a confined space. (+info)
Induction of genetic damage in human lymphocytes and mutations in Salmonella by trihalomethanes: role of red blood cells and GSTT1-1 polymorphism.
The brominated trihalomethanes (THMs) are mutagenic and carcinogenic disinfection by-products frequently found in chlorinated drinking water. They can be activated to mutagens by the product of the glutathione S-transferase-Theta (GSTT1++-1) gene in Salmonella RSJ100, which has been transfected with this gene. To evaluate this phenomenon in humans, we have examined the genotoxicity of a brominated THM, bromoform (BF), using the Comet assay in human whole blood cultures exposed in vitro. No differences were found in the comet tail length between cultures from GSTT1-1(+) versus GSTT1-1(-) individuals (1.67 +/- 0.40 and 0.74 +/- 0.54 microm/mM, respectively, P = 0.28). The high variability was due to the relatively weak induction of comets by BF. Combining the data from both genotypic groups, the genotoxic potency of BF was 1.20 +/- 0.34 microm/mM (P = 0.003). GSTT1-1 is expressed in red blood cells but not in the target cells (lymphocytes), and expression within the target cell (as in Salmonella RSJ100) may be necessary for enhanced mutagenesis in GSTT1-1(+) relative to GSTT1-1(-) cultures. To examine this, we exposed Salmonella RSJ100 and a control strain not expressing the gene (TPT100) to the most mutagenic brominated THM detected in Salmonella, dibromochloromethane (DBCM), either in the presence or absence of S9 or red blood cells from GSTT1-1(+) or GSTT1-1(-) individuals. S9 did not activate DBCM in the non-expressing strain TPT100, and it did not affect the ability of the expressing strain RSJ100 to activate DBCM. As with S9, red cells from either genotypic group were unable to activate DBCM in TPT100. However, red cells (whole or lysed) from both genotypic groups completely repressed the ability of the expressing strain RSJ100 to activate DBCM to a mutagen. Such results suggest a model in which exposure to brominated THMs may pose an excess genotoxic risk in GSTT1-1(+) individuals to those organs and tissues that both express this gene and come into direct contact with the brominated THM, such as the colon. In contrast, those organs to which brominated THMs would be transported via the blood might be protected by erythrocytes. Such a proposal is reasonably consistent with the organ specificity of drinking water-associated cancer in humans, which shows slightly elevated risks for cancer of the colon and bladder but not of the liver. (+info)
Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer.
The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2,434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1,983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and > or =40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates. (+info)
Investigation of an acute chemical incident: exposure to fluorinated hydrocarbons.
OBJECTIVES: To assess whether attendance at the site after an incident in a sewer was associated with symptoms in emergency personnel and whether the prevalence of symptoms was associated with estimated levels of exposure to any chemical hazard. METHODS: Symptoms experienced by people attending an incident involving two dead sewer workers suggested the presence of a chemical hazard, before environmental sampling confirmed any toxic agent. Self reported symptoms, estimated exposures, and biomarkers of exposure for likely agents from all 254 people who attended the incident and a referent occupational group matching the 83 emergency personnel who went to the Accident and Emergency department (A and E) in the first 48 hours were recorded. The prevalence of symptoms and concentrations of creatine phosphokinase in serum of the 83 early patients at A and E were compared with their referent occupational group. In all workers who attended the incident, the trends in symptom prevalences and concentrations of creatine phosphokinase in serum were examined by distance from the site and predefined exposure category. RESULTS: Among all workers who attended the incident, symptoms of shortness of breath and sore throat were significantly associated with indirect estimates of exposure but not associated with concentrations of creatine phosphokinase. Freon was detected in two blood samples. The early patients at A and E reported more symptoms than their matched reference group and their median concentrations of creatine phosphokinase were higher. CONCLUSIONS: The association between symptoms and concentrations of creatine phosphokinase with attendance at the site indicated the presence of a continuing hazard at the site and led to extra precautions being taken. Comparison values from the referent occupational group prevented unnecessary medical follow up. (+info)
Effect of dichlorodifluoromethane on the appearance, viability, and integrity of Escherichia coli.
Cultures of Escherichia coli H52 were treated with liquid dichlorodifluoromethane (fluorocarbon-12 [f-12]) for 2 h at 22 C and then examined microscopically. Treated cells tended to clump, and their cytoplasms were generally less dense and less uniform in appearance than those of control cells. E. coli ML30 was exposed to f-12 at a concentration of 1.25 X saturation for times up to 1,200 min at 22 C. Cells were examined for changes in viability (plate count), permeability (as measured by exit of alpha-[14-C]methylglucoside or uptake of omicron-nitrophenyl-beta-D-galactopyranoside), release of compounds absorbing at 260 nm, and lysis (changes in absorbance at 420 nm). Large losses of alpha-methylglucoside and of percentage of viability occurred after brief exposure to f-12. Release of compounds absorbing at 260 nm occurred more slowly than the aforementioned events, possibly because these molecules are larger than alpha-methylglucoside. During 1,200-min exposure to f-12, the number of survivors decreased from 10-9 to 10-4 organisms/ml, the loss of compounds absorbing at 260 nm amounted to 50 percent, and 32 percent lysis occurred. Most of these changes occurred during the first 300 min of treatment. Loss of alpha-methylglucoside was almost complete after 1-min exposure to f-12. These results suggest that death of the cell involves several stages, with a change of permeability, occurring first, followed by leakage of compounds of increasing size and, finally, lysis. (+info)
Comparative effects of anesthetics on the viability and integrity of Escherichia coli ML30.
Cells of Escherichia coli ML30 in a mineral salts medium were exposed to dichlorodifluoromethane (f-12), cyclopropane, halothane, or Ethrane at concentrations of 1.25, 0.2, 0.04, and 0.008 X saturation for times up to 1,200 min, and at temperatures in the range of 2 to 37 C. When any of these anesthetics were applied for 300 min at 1.25 X saturation, a substantial decrease in number of survivors occurred. Halothane was most bactericidal, cyclopropane and Ethrane were moderately bactericidal, and t-12 was least bactericidal. At saturation values of less than 1.0, none of the four anesthetics had an appreciable effect on viability of E. coli. Greatest increases in cell permeability occurred when anesthetics were used at saturation values of 1.25, and permeability changes generally decreased as the concentrations of the chemicals were reduced. In many instances, anesthetics in the vapor state caused significant increases in cell permeability but little or no loss of viability. This indicated that a close relationship did not exist between loss of viability and increased permeability. All four anesthetics caused E. coli to lose substantial and similar amounts of compounds absorbing at 260 nm. Release of compounds absorbing at 260 nm generally increased as the saturation value of a given chemical was increased. Halothane, Ethrane, and cyclopropane but not f-12 caused lysis of E. coli ML300. Considering all results, E. coli ML30 was damaged more by halothane or cyclopropane than by f-12 or Ethrane. When f-12 was applied at a saturation value of 1.25, the bactericidal effect on E. coli was much greater at 37 or 22 C than at 12 or 2 C. (+info)
Delivery of fenoterol via Respimat, a novel 'soft mist' inhaler. a randomised, double-blind (within device), placebo-controlled, cross-over, dose-ranging study in asthmatic patients.
BACKGROUND: The phase-out of chlorofluorocarbons (CFCs) for metered dose inhalers (MDIs) has prompted the development of alternative propellants and the design of propellant-free devices for inhalation therapy. OBJECTIVE: This study was carried out to determine the dose of fenoterol inhaled from Respimat (RMT), a new propellant-free soft mist inhaler, which is equivalent in terms of efficacy and safety to 1 puff of either 100 or 200 microg fenoterol inhaled from a conventional CFC-MDI (Berotec). METHODS: Sixty-two asthmatic patients (35 male, 27 female) with a mean baseline FEV(1) of 1.7 liters, corresponding to 55% of the predicted normal value, were randomized at two study centers to 4 of a total of 8 possible treatments: placebo; 12.5, 25, 50, 100, or 200 microg fenoterol via RMT, and 100 or 200 microg fenoterol delivered via the MDI. RESULTS: Fifty-nine patients completed the study as planned. Results of the therapeutic equivalence test for the primary endpoint, average FEV(1) (AUC(0-6))/6 and for the secondary endpoint, peak FEV(1), showed that the 12.5- and 25-microg fenoterol doses administered via RMT were equivalent to the 100 microg fenoterol dose from the MDI. The 50-, 100- and 200-microg fenoterol doses delivered by RMT did not meet the criterion for therapeutic equivalence with the 100-microg dose from the MDI, and if tested for a difference would have been significantly different in favor of RMT. All 5 RMT fenoterol doses were therapeutically equivalent to the MDI 200-microg fenoterol dose. Headache, reported by 4 patients on test days and 2 patients between test days in those randomized to RMT, was the most common adverse event, but the active treatments were generally well tolerated with no dose-dependent increases in incidence or severity of adverse events observed. CONCLUSIONS: The results from the study suggest that safe and efficacious bronchodilation can be obtained from single-dose fenoterol administered via RMT. Use of lower absolute doses to obtain a clinically significant improvement in pulmonary function may be possible because of the increased lung deposition achievable with the novel soft mist inhaler. (+info)
Biotransformation and elimination of 14C-trichlorofluoromethane (FC-11) and 14C-dichlorodifluoromethane (FC-12) in man.
Radiocarbon-labeled trichlorofluoromethane (FC-11; 14CC13F) and dichlorodifluormethane (FC-12; 14CC12F2) were separately inhaled by a female subject and a male subject. A predetermined volume of fluorocarbon (1000 ppm; 100 muCi) in air was delivered through a nonrebreating system and a tight-fitting face mask for 7-17 minutes. Total expired gases were collected during fluorocarbon exposure and afterward until no radioactivity was detectable. Expired 14CO2 and 14C-fluorocarbon were assayed. Urine was collected for 72 hours and assayed for nonvolatile radioactivity. Total recoveries of FC-11 were 99.5 and 79.4 per cent in the woman and the man, respectively. Total recoveries of FC-12 were 95.4 and 103.2 per cent. Traces of radioactivity were found in urine (FC-11, 0.07 and 0.09 per cent; FC-12, 0.02 and 0.03 per cent) and in exhaled carbon dioxide (FC-11, 0.13 and 0.10 per cent; FC-12, 0.08 per cent in both subjects). Total metabolites were equal to or less than 0.2 per cent of the administered dose. The amount of radioactivity in urine was insufficient to permit identification of possible fluorocarbon metabolites. The trace of metabolites could be products of radiolabeled impurities. (Key words: Gases, non-anesthetic, dichlorodifluoromethane (Freon 12); Gases, non-anesthetic, trichlorofluoromethane (Freon 11); Pharmacology, fluorocarbons.) (+info)