Inability of GSTT1 to activate iodinated halomethanes to mutagens in Salmonella.

Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 µmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water.

A comparative study of patients' preferences and sensory perceptions of three forms of inhalers among Thai asthma and COPD patients.

In 9 study centers, 419 patients with asthma or COPD were randomized to receive two forms of salbutamol metered-dose-inhalers (MDIs), i.e. CFC-driven MDI, non-CFC (HFA) MDI and one salbutamol dry powder inhaler (DPI), in a multi-center, comparative, cross-over and randomized study, performed to facilitate the formulation of a strategic plan to phase out CFC MDIs. After having received all three forms of test products, the patients completed an evaluation questionnaire indicating their preferences, likelihood of treatment compliance on each product and the easiest one to use. Statistical analysis showed that the CFC MDI was significantly less irritating (p < 0.014) but lower in its overall appeal (p < 0.0001). The "most preferred form to be prescribed" was DPI at 47.5% followed by non-CFC at 32.5% and CFC MDI at 20.1%. Concerning the ease of use among the three forms of test products, 59.9% of the patients indicated "no difference". Adverse events were mild and occurred in only 8.2%. In conclusion, patients' preference and sensory perception among the three forms of inhalers were comparable except that the CFC MDI was significantly less irritating but lower in its overall appeal. DPI was the most preferred and easiest form to use but also the most expensive. Taking public health into consideration, a non-CFC MDI with a similar market price to the CFC MDI would be the obvious choice in a strategic plan to phase out CFC MDIs with the least difficulty to the consumers.

A proposed mechanism for cardiac sensitisation: electrophysiological study of effects of difluorodichloromethane and adrenaline on different types of cardiac preparations isolated from sheep hearts.

Difluorodichloromethane (FC12) inhaled at high concentrations sensitises, as do numerous other volatile organic compounds, mammalian heart to adrenaline induced arrhythmias. In this study three types of cardiac tissue (spontaneously beating sinusal and Purkinje preparations and stimulated Purkinje fibres) were isolated from sheep hearts and perfused for electrophysiological recording to examine the effect of FC 12. Preparations were perfused alternately with a control solution of physiological fluid and a trial solution with dissolved FC 12, the partial pressure of oxygen remaining identical. Sensitisation to adrenaline was studied by injecting adrenaline at a dose causing a notable effect without producing arrhythmias in the control preparations. Examination of transmembrane potential recordings confirmed that FC 12 inhibits sinus node pacemaker stimulation by adrenaline. Conversely, the adrenaline induced acceleration of latent pacemakers in certain types of Purkinje fibres appeared to be potentialised by FC 12. The various types of arrhythmia observed in vitro were explained by the effect of FC 12 on cell membranes, an affect which can oppose or favour that of adrenaline. These phenomena explain the arrhythmias observed in isolated hearts or whole animal preparations and permit a better understanding of the mechanism involved in cardiac sensitisation to adrenaline induced arrhythmia, a mechanism in which variability in time and location is the essential factor in the FC 12 effect.

Drinking water and pregnancy outcome in central North Carolina: source, amount, and trihalomethane levels.

In spite of the recognition of potentially toxic chemicals in chlorinated drinking water, few studies have evaluated reproductive health consequences of such exposure. Using data from a case-control study of miscarriage, preterm delivery, and low birth weight in central North Carolina, we evaluated risk associated with water source, amount, and trihalomethane (THM) concentration. Water source was not related to any of those pregnancy outcomes, but an increasing amount of ingested water was associated with decreased risks of all three outcomes (odds ratios around 1.5 for 0 glasses per day relative to 1-3 glasses per day, falling to 0.8 for 4+ glasses per day). THM concentration and dose (concentration x amount) were not related to pregnancy outcome, with the possible exception of an increased risk of miscarriage in the highest sextile of THM concentration (adjusted odds ratio = 2.8, 95% confidence interval = 1.1-2.7), which was not part of an overall dose-response gradient. These data do not indicate a strong association between chlorination by-products and adverse pregnancy outcome, but given the limited quality of our exposure assessment and the increased miscarriage risk in the highest exposure group, more refined evaluation is warranted.

Posterior lip traction caused by intravitreal gas.

Traction on the posterior edge of a large tear may be an irreparable consequence of an intraocular gas tamponade used in the first instance to treat the tear. In two of three patients treated with octofluorocyclobutane (C4F8) and perfluoromethane (CF4), redetachment of a retinal tear occurred as a result of traction on the posterior edge of the tear when, prior to the operation, the posterior edge seemed to be free of any traction. With redetachment, a membrane became visible between the anterior and posterior lips of the tear. The membrane was probably posterior hyaloid augmented by cellular proliferation. The gas bubble, which had been intended to press the retina against the pigment epithelium, probably brought the detached posterior hyaloid into contact with the retina as well, and an adhesion between the hyaloid and retina formed.

Use of a job-exposure matrix to assess occupational exposures in relation to birth defects.

Accurate exposure assessment remains a challenge in occupational epidemiology. We evaluated one approach, use of a job-exposure matrix (JEM), by applying the National Institute for Occupational Safety and Health (NIOSH) JEM to a large case-control birth defects study that included parental occupation information. We investigated the JEM exposure predictions in several ways and found that for a substantial proportion of the parents in the birth defects study, the JEM yielded either no exposure data or nonsense predictions. Among exposure predictions that were plausible, most were of low probability. The high probability exposure predictions were statistically unstable, and neither low nor high probability exposure predictions were reliable. There was considerable discrepancy between the JEM predictions and expert assessments for five exposures of interest. Application of the NIOSH JEM to the birth defects study database (and probably other databases as well) does not provide a useful means of assessing occupational exposures.

Prolonged respiratory symptoms caused by thermal degradation products of freons.

OBJECTIVES: The chlorofluorocarbons (CFC) used in refrigeration systems decompose on heating and produce substances that are highly irritating to the airways (eg, chlorine, carbonyl fluoride, and hydrogen fluoride). This study examined persistent respiratory symptoms among several workers exposed to thermal decomposition products of CFC. METHODS: Seven patients with respiratory symptoms caused by inadvertent exposure to thermal decomposition products of CFC in a restaurant kitchen or during refrigerator repair were studied with the use of spirometry, peak flow follow-up, and histamine challenge tests. Three patients also underwent bronchoscopy and bronchoalveolar lavage. RESULTS: In five of the cases, cough or dyspnea lasted longer than 1 month; for three of the five, the symptoms lasted more than 4 years. Three cases showed increased bronchial hyperreactivity, and two of the three had increased diurnal peak flow variation. Three patients fulfilled the criteria for acute irritant-induced asthma or reactive airway dysfunction syndrome. One case exhibited bronchiolitis while, for the other six, the clinical picture was consistent with bronchitis. CONCLUSIONS: The studied cases indicate that the thermal decomposition products of CFC used in refrigerators may cause irritant-induced airway diseases of long duration.

Inhalation of decomposed chlorodifluoromethane (freon-22) and myocardial infarction.

After exposure to decomposed chlorodifluoromethane (freon-22), a 65-year-old man developed respiratory symptoms such as cough, blood-stained sputum, and increasing dyspnea. Three weeks later, his family doctor diagnosed infectious bronchitis. Another week later he died due to myocardial infarction. The discussion focuses on an inflammatory process caused by the inhalation of decomposed freon and its possible association with myocardial infarction.

The volume of gas emitted from five metered dose inhalers at three levels of fullness.

UNLABELLED: We conducted this study to determine the volume of gas emitted from five commonly used metered dose inhalers (MDIs). MATERIALS & METHODS: We used the following MDIs: Alupent (Boehringer Ingelheim), Atrovent (Boehringer Ingelheim), Beclovent (Allen & Hanburys), Intal (Fisons), and Ventolin (Allen & Hanburys). The test system consisted of plastic bag, MDI adapter, 4-way stopcock, and 60-mL calibrated syringe. This system was glued together, and absence of leaks was confirmed by underwater testing. Each evaluation consisted of 10 puffs from the MDI into the bag, after which the volume in the bag was determined using the syringe, and the volume/puff was calculated by dividing by 10. Each MDI was evaluated at 3 levels of fullness: nearly full, partially empty, and nearly empty. Five measurements were made with each MDI brand, using a new MDI for each set of measurements. RESULTS: Although there was a significant difference in the volumes emitted between MDI (p less than 0.001) and the levels of fullness (p = 0.001), the volume of gas emitted from these MDIs was small (approximately 15-20 mL). A significant interaction existed between MDI brand and level of fullness (p = 0.001). CONCLUSIONS: Based on prior studies of propellant toxicity coupled with our findings on the volumes of gas emitted from MDIs, we conclude that the volumes of gas emitted are too small to be clinically important in the care of adult patients. The volume of gas emitted from an MDI is only potentially important if MDIs are used with very small tidal volumes in a closed system (eg. infants).

Facial injury and airway threat from inhalant abuse: a case report.

Fluorinated hydrocarbons cause toxicity in humans via their dysrhythmogenic potential and their local physical effects on the skin and mucous membranes. The former is generally the more life-threatening toxic consequence. We present a case of fluorinated hydrocarbon injury resulting from an intentional inhalation exposure that created facial frostbite, which threatened the patient's airway. The clinical range and management of these tissue-toxic effects are reviewed.

Frostbite of the mouth: a case report.

A case report is presented of a young male who sustained a second-degree frostbite injury to the oral cavity, to include lower lip, hard palate, tongue, and buccal mucosa. This unusual injury occurred as a result of substance abuse: an attempt to inhale an aerosolized propane propellant as a means to achieve euphoria.

Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants.

Metered-dose inhalers are frequently used in treating pulmonary diseases associated with bronchoconstriction, chiefly asthma and chronic bronchitis. These aerosolized medications are not without the potential for adverse effects. The author describes two patients who likely had adverse reactions to the Freon propellants used in the inhalers. These reactions are reported in order to alert physicians to their possible occurrence and to suggest a rational treatment approach.

[Chlorofluorocarbons--a new environmental health problem]. / Klorofluorougljici--novi ekoloski zdravstveni problem.

A review of health problems caused by the use of chlorofluorocarbons--chemical substances of widespread and varied applications is presented. There is a recent evidence that fully halogenated chlorofluorocarbons are air pollutants inducing hazardous health effects. Direct effects of chlorofluorocarbons on respiratory and cardiac functions are described among which some with lethal outcome. Recent data are given and models described forecasting indirect effects of chlorofluorocarbons induced by their ozone depleting reactions in the stratosphere which bring about a higher exposure of the population to UV-B radiation. As a consequence of which, an increase of the incidence of nonmelanoma and melanoma skin cancers, immunosuppression, and eye disorders is predicted. The latest international activities aimed at urgent prevention of these effects are described.

[Freon gas frostbite: an unusual burn evolving in two stages]. / Gelure au gaz fréon : une brulure atypique évoluant en deux temps.

Freon gas is a halogenated derivative widely used in refrigeration and air conditioning. It is maintained at a temperature below -41°C and its contact with skin may cause very serious burns. This is usually an accident at work and the burns affect the hands of patients first. Unfortunately, early clinical presentation is often reassuring and does not reflect the actual depth of the injury. Few cases of this injury are reported and no treatment protocol is established at this time. We present two cases of frostbite by freon gas, initially evaluated at a stage of superficial burns and evolved spontaneously in a few days to full thickness burns necessitating surgical treatment by excision and skin grafting. This evolution in two phases has never been described and could help to better understand the pathophysiology of this frostbite and the possibilities of management.