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[A quantitative assessment of health risk induced by occupational exposure to inorganic arsenic].

The risk of neoplastic disease, primarily lung cancer, induced by occupational, inhalation exposure to nonorganic arsenic was assessed. In order to identify individual risk in the linear dose-response relationship which would serve as a basis for the risk assessment among persons exposed occupationally, the author also analysed the latest epidemiological studies performed in Sweden, as well as repeated analyses of American studies. This allowed to diminish individual risk by several times. It is thought that a diminished value of individual risk is, in the light of the most up-to-date epidemiological studies, closer to the reality than the value proposed by the Environmental Protection Agency (EPA). Having the value of individual risk related to occupational exposure, equal 1.79 x 10(-4), lung cancer risk after forty years of employment under the exposure level within the range of currently binding MAC values for arsenic (0.05 mg/m3) accounts for 8.95 x 10(-3), thus slightly exceeding the adopted value of 1 x 10(3). Whereas a new value, proposed by the Expert Group for Chemical Factors of the International Commission for Updating the list of MAC and MAI values in 1996, equals 0.01, so the risk for a forty-year employment accounts for 1.79 x 10(-3), in fact the value corresponding to that already approved. In addition, the assessment indicated that smoking increases by 4-6 times the risk of lung cancer induced by exposure to arsenic.

Air Pollutants, Occupational↗

[The prevention of autoimmune kidney lesions developing in long-term exposure to epoxy compounds].

Clinical and biochemical, immunological and histological studies made in animals under inhalation exposure to volatile components of a new epoxy resin have yielded evidence in support of the development of autoimmune pathology (glomerulonephritis). One-stage determination of the amount of the blood serum circulating immune complexes and of the degree of sensibilization of bodily immunocompetent cells to a chemical (epichlorhydrin) and tissue (kidney) allergens in whole blood are regarded as a test for early diagnosis of glomerulonephritis. The enterosorbent "Ensoral" inhibits the development of those autoimmune processes being caused by bodily exposure to high concentrations of volatile components of epoxy resins.

Air Pollutants, Occupational↗

Deposition of dibasic esters in the upper respiratory tract of the male and female Sprague-Dawley rat.

Inhalation exposure of the male and female rat to high concentrations of a mixture of the dibasic esters dimethyl succinate (DMS), dimethyl glutarate (DMG), and dimethyl adipate (DMA) results in mild olfactory toxicity. This response is thought to be due to the in situ formation of acidic metabolites via nasal carboxylesterases. The current study was designed to provide inhalation dosimetric information for these vapors. Deposition of DMS, DMG, and DMA was measured in the surgically isolated upper respiratory tracts (URT) of ketamine-xylazine-anesthetized male and female rats under constant velocity flow conditions at a flow rate of 100 ml/min. Deposition of acetone was measured in both genders for comparative purposes. URT deposition efficiencies in excess of 98.3% were observed for DMS, DMG, and DMA in animals exposed to each vapor individually. No gender differences in deposition efficiency were observed for these vapors or for acetone. Deposition of DMS, DMG, and DMA was also measured in animals exposed to all three vapors simultaneously. Deposition efficiency under simultaneous exposure conditions ranged between 97.3 and 98.5%. These values were slightly lower (about 1%) than those obtained under individual exposure conditions (p less than 0.0001). The reduced deposition efficiency may have resulted from competitive inhibition of nasal metabolism due to the simultaneous presence of all three carboxylesterase substrate vapors in nasal tissues. If so, inhalation of dibasic ester vapors would be expected to inhibit the uptake of other carboxylesterase substrate vapors without influencing uptake of vapors which are not substrates for this enzyme. Such was observed in studies using DMS, ethyl acetate (the substrate vapor), and isoamyl alcohol (the nonsubstrate vapor). Specifically, simultaneous exposure to DMS markedly inhibited uptake of ethyl acetate without altering uptake of isoamyl alcohol. Gender differences were not observed in URT deposition of any of the six vapors used in the current study, DMS, DMG, DMA, ethyl acetate, isoamyl alcohol, or acetone, suggesting that gender differences in URT deposition may not be widespread among vapors. The high URT deposition efficiencies of the dibasic esters are consistent with the olfactory toxicity resulting from inhalation exposure to these vapors.

Acetates↗

Evaluation of dermal and respiratory chloroform exposure in humans.

Chloroform is a known contaminant of chlorinated drinking water and of swimming pool water disinfected with chlorine or one of its derivatives. Few data exist regarding the importance of dermal and inhalation exposure routes to the chloroform body burden resulting from domestic and recreational use of chlorinated water. In our experimental study involving 11 male swimmers, we quantified the body burden resulting from exposure to various concentrations of chloroform in water and air of an indoor swimming pool, during a daily 55-min exercise period. From the first to the sixth exercise period, CHCl3 mean concentration in water was increased from 159 micrograms/l to 553 micrograms/l. Corresponding mean air CHCl3 level ranged from 597 ppb to 1630 ppb. To dissociate the dermal exposure route from that of inhalation, swimmers used scuba tanks during an additional exercise period. Chloroform concentrations were measured in alveolar air before and after each exercise period, as well as after 35 min of physical activity. Chloroform levels in water and air were measured every 10 min. We examined the relationship between alveolar air concentration (a measure of body burden) at 35 and 55 min and environmental chloroform concentrations by using multiple regression models. The natural logarithm of alveolar air concentration was strongly correlated with aqueous chloroform concentration both at 35 (p2 < 0.001, r2 = 0.75) and 55 min (p < 0.001, r2 = 0.86). The relationship with air concentrations was also statistically significant (35 min: p < 0.001, r2 = 0.58, 55 min: p < 0.001, r2 = 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

[An experimental study of the effect of an artichoke preparation on the activity of the sympathetic-adrenal system in carbon disulfide exposure].

Artichoke, a new Bulgarian preparation based on the plant Cynara scolymus, was tested for influence on sympatho-adrenal system (SAS) activity in experimental inhalation exposure to carbon disulfide. This chronic (six-month) inhalation experiment was done on Wistar albino rats of either sex. Activity of SAS was assessed through excretion of noradrenalin and adrenalin. Findings indicated a phasic SAS response depending on concentration and duration of carbon disulfide exposure. With exposure to 30 mg.m3, SAS activity was observed to decrease in the second month, followed by increase in the fourth and sixth months. With exposure to 300 mg.m3, SAS activity was elevated over the whole period of study. Under the influence of the preparation artichoke at dosage 200 mg.kg-1, catecholamines, increased by carbon disulfide exposure, returned to normal. This trend was more marked for noradrenalin.

Adrenal Glands↗

Cellular kinetics in the lungs of aging Fischer 344 rats after acute exposure to ozone.

Lung repair in aging Fischer 344 male rats was investigated after an acute inhalation exposure to ozone. Adult (9-month-old) and senescent (24-month-old) rats were exposed to 0.8 ppm ozone for a single period of 6 hours, and thereafter studied over 5 days of recovery in clean air. The animals were given intraperitoneal injections of colchicine and [3H]thymidine, 4 hours and 1.5 hours before termination, respectively. The lungs were inflated with glutaraldehyde, and tissue samples were embedded in epoxy resin for electron microscopy, or in glycol methacrylate for light-microscopic autoradiography. Exposure to ozone produced epithelial injury in alveolar ducts and terminal bronchioles, later reflected by the transient increase in mitotic activity of nonciliated bronchiolar cells and alveolar type 2 cells. The increase in metaphase-arrested cells and [3H]thymidine-labeled cells in bronchioles followed similar time courses, ie, maximal at days 1.5 to 2, and subsiding by day 3. In the alveoli, type 1 cell necrosis was observed early after exposure (6 hours recovery), without notable structural changes in the interstitial and endothelial compartments. The increased mitotic activity in the alveolar septa was mostly due to proliferation of epithelial type 2 cells, which was maximal at day 1.5, and of interstitial cells, maximal at day 2.5. The magnitude of the mitotic responses of nonciliated bronchiolar cells, alveolar type 2 cells and interstitial cells was highest (+50%) in the lungs of senescent rats. Although the cellular events during repair are essentially similar in both age groups, the results indicate that senescent rats have a significantly higher level of initial injury from inhalation of ozone than adult animals.

Administration, Inhalation↗

Inhalation studies in laboratory animals--current concepts and alternatives.

Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and to fulfill general regulatory requirements for the registration of new drugs, pesticides, or chemicals. Despite significant efforts, the results of inhalation studies have to be analyzed judiciously due to the great number of variables. These variables may be related to technical issues or to the specific features of the animal model. Although inhalation exposure of animals mimics human exposure best, ie, error-prone route-to-route extrapolations are not necessary, not all results obtained under such very rigorous test conditions may necessarily also occur under real-life exposure conditions. Attempts are often made to duplicate as closely as possible these real-life exposure conditions of humans in appropriate bioassays. However, this in turn might affect established baseline data, rendering the interpretation of new findings difficult. In addition, specific use patterns, eg, of inhalation pharmaceuticals or pesticide-containing consumer products, may impose test agent-specific constraints that challenge traditional approaches. Moreover, specific modes of action of the substance under investigation, the evaluation of specific endpoints, or the clarification of equivocal findings in common rodent species may require exposure paradigms or the use of animal species not commonly used in inhalation toxicology. However, particularly in inhalation toxicology, the choice of animal models for inhalation toxicity testing is usually based on guideline requirements and practical considerations, such as exposure technology, expediency, and previous experience rather than validity for use in human beings. Larger animal species, apart from the welfare aspects, may require larger inhalation chambers to accommodate the animals, but for technical reasons and the difficulty of generating homogeneous exposure atmospheres in such inhalation chambers, this may jeopardize the outcome of the study. Some of the many variables and possible artifacts likely to occur in animal inhalation studies are addressed in this paper.

Administration, Inhalation↗

Video methods in the quantification of children's exposures.

In 1994, Stanford University's Exposure Research Group (ERG) conducted its first pilot study to collect micro-level activity time series (MLATS) data for young children. The pilot study involved videotaping four children of farm workers in the Salinas Valley of California and converting their videotaped activities to valuable text files of contact behavior using video-translation techniques. These MLATS are especially useful for describing intermittent dermal (i.e., second-by-second account of surfaces and objects contacted) and non-dietary ingestion (second-by-second account of objects or hands placed in the mouth) contact behavior. Second-by-second records of children contact behavior are amenable to quantitative and statistical analysis and allow for more accurate model estimates of human exposure and dose to environmental contaminants. Activity patterns data for modeling inhalation exposure (i.e., accounts of microenvironments visited) can also be extracted from the MLATS data. Since the pilot study, ERG has collected an immense MLATS data set for 92 children using more developed and refined videotaping and video-translation methodologies. This paper describes all aspects required for the collection of MLATS including: subject recruitment techniques, videotaping and video-translation processes, and potential data analysis. This paper also describes the quality assurance steps employed for these new MLATS projects, including: training, data management, and the application of interobserver and intraobserver agreement during video translation. The discussion of these issues and ERG's experiences in dealing with them can assist other groups in the conduct of research that employs these more quantitative techniques.

California↗

Epidemiology of allergic rhinitis and its associated risk factors in Singapore.

BACKGROUND: Few studies have evaluated the relationship between allergic rhinitis and risk factors in the environment which promote aeroallergenic exposures, but knowledge of these are of practical importance from the point of view of community prevention. METHOD: A cross-sectional population-based study of 2868 adults aged 20-74 years was carried out. Allergic rhinitis was defined as the self-reported presence, in the previous year, of usual nasal blockage and discharge apart from colds or the flu, provoked by allergens, with or without conjunctivitis. RESULTS: Allergic rhinitis was reported by 4.5% of the subjects. Higher crude prevalences were observed in males, younger adults, Indians compared to Chinese and Malays, those with higher socioeconomic status, and in three of five residential areas studied. Significant environmental factors included cockroach infestation, occupational exposure, past smoking habit, outdoor air pollution, and frequent heavy exposure to cooking fumes. Keeping pets, having rugs or carpets in the home, and passive exposure to tobacco smoke showed weak and statistically insignificant associations. There was no apparent association with use of mosquito coils or incense. The significant determinants after multivariate adjustment of all risk factors were age, race, flat size, area of residence, cockroach infestation, past smoking, and occupational and cooking fumes exposure. CONCLUSION: The study underscores the importance of environmental control of inhalational exposure to common allergens and irritants in the prevention of allergic rhinitis.

Adult↗

Review of the U.S. Army's health risk assessments for oral exposure to six chemical-warfare agents. Introduction.

The U.S. Army is under a congressional mandate and the Chemical Weapons Convention of January 1993 to destroy its entire stockpile of chemical munitions. In addition to stockpiled munitions, nonstockpile chemical materiel (NSCM) has been identified for destruction. NSCM includes a host of lethal wastes from past disposal efforts, unserviceable munitions, chemically contaminated containers, chemical-production facilities, newly located chemical munitions, known sites containing substantial quantities of buried chemical weapons and wastes, and binary weapons and components. There are eight stockpile sites located in the continental United States and one on an island in the Pacific Ocean, and 82 NSCM locations have been identified. There are concerns, based on storage and past disposal practices, about soil and groundwater contamination at those sites. Six of the most commonly found chemical-warfare agents at stockpile and NSCM sites are the nerve agents GA, GB, GD, and VX and the vesicating (blistering) agents sulfur mustard and lewisite. To ensure that chemical contamination is reduced to safe concentrations at stockpile and NSCM sites before they are used for residential, occupational, or wildlife purposes, the U.S. Army requested that health-based exposure limits for GA, GB, GD, VX, sulfur mustard, and lewisite be developed to protect the public and the environment. Oak Ridge National Laboratory (ORNL) was asked to conduct the health risk assessments and propose chronic oral reference doses (RfDs) and, where appropriate, oral slope factors (SFs) for the six agents. RfDs are toxicological values developed for noncancer effects and used as reference points to limit human oral exposure to potentially hazardous concentrations of chemicals thought to have thresholds for their effects. RfDs are estimates (with uncertainty spanning an order of magnitude or greater) of daily oral chemical exposures that are unlikely to have deleterious effects during a human lifetime. For chemicals identified as carcinogens (e.g., sulfur mustard), SFs are also calculated. SFs are estimates of upper-bound lifetime cancer risk from chronic exposure to an agent. The Army's Surgeon General adopted the proposed RfDs and SFs developed by ORNL as interim values to ensure that consistent health-based criteria were applied in ongoing initiatives requiring decisions on the safety of contaminated sites. The Army's Surgeon General also requested that the National Research Council (NRC) independently review the scientific validity of these values. The NRC assigned this task to the Committee on Toxicology (COT), and a multidisciplinary subcommittee of experts was convened to assess the scientific validity of the interim RfDs developed for GA, GB, GD, VX, sulfur mustard, and lewisite and the SF developed for sulfur mustard. Specifically, the subcommittee was asked to (1) determine whether all the relevant toxicity data were considered appropriately; (2) review the uncertainty, variability, and quality of the data; (3) determine the appropriateness of the assumptions used to derive the RfDs (e.g., the application of uncertainty factors); and (4) identify data gaps and make recommendations for future research. Although multiple agents are present at stockpile and NSCM sites, the subcommittee was asked to evaluate the agents only on an individual basis. Furthermore, although the most likely routes of exposure to chemical-warfare agents at these sites are the inhalation and dermal routes, the subcommittee was only asked to evaluate toxicological risk from the oral route at this time. The Army is in the process of developing inhalation exposure guidelines. The subcommittee was also not asked to address issues related to risk management, such as technology, detection, and feasibility.

Administration, Oral↗

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat.

BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.

Abnormalities, Drug-Induced↗

Calculation of exposure chamber leak rate with thermal correction: a measure of chamber integrity.

A method for assessing inhalation exposure chamber integrity by calculation of leak rate was modified to account for temporal changes of temperature in the chamber. In a well-sealed chamber, accounting for thermal effect brought observed leak rates into better agreement with predicted values. Mean estimates of chamber leak rate without thermal correction ranged from 2.9 to 40.6 cm3/min whereas those with thermal correction ranged from 9.6 to 14.3 cm3/min. The average change in estimate of chamber leak rate brought about by correcting for thermal effect was 16.8 cm3/min per K change of temperature in the chamber. Accounting for thermal effect reduced the coefficient of variation for repeated estimates (n = 10) of chamber leak rate from 65 to 15%. The use of temperature-corrected calculation of chamber leak rate minimizes thermal artifact thereby improving decisions about chamber operation based on assessment of chamber integrity.

Air Pollutants, Occupational↗

Mycotoxin adducts on human serum albumin: biomarkers of exposure to Stachybotrys chartarum.

OBJECTIVE: Despite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys chartarum, controversy remains. Currently, there are no reliable assays suitable for clinical diagnosis of exposure. We hypothesized that satratoxin G (SG) -albumin adducts may serve as biomarkers of exposure to this fungus. DESIGN: We studied the formation of adducts of SG with serum albumin in vitro using Western blots and mass spectrometry (MS) and searched for similar adducts formed in vivo using human and animal serum. RESULTS: Samples of purified human serum albumin that had been incubated with increasing concentrations of SG showed concentration-dependent albumin bands in Western blots developed with anti-SG antibodies. MS analysis found that as many as 10 toxin molecules can be bound in vitro to one albumin molecule. The sequencing of albumin-adduct tryptic peptides and the analysis of pronase/aminopeptidase digests demonstrated that lysyl, cysteinyl, and histidyl residues are involved in the formation of these adducts. Serum samples from three patients with documented exposure to S. chartarum similarly revealed lysine-, cysteine-, and histidine-SG adducts after exhaustive digestion, affinity column enrichment, and MS analysis. These adducts were also found in the sera from rats exposed to the spores of S. chartarum in contrast to control human subjects and control animals. CONCLUSIONS: These data document the occurrence of SG-albumin adducts in both in vitro experiments and in vivo human and animal exposures to S. chartarum. RELEVANCE TO CLINICAL PRACTICE: SG-amino acid adducts may serve as reliable dosimeter biomarkers for detection of exposure to S. chartarum.

Amino Acid Sequence↗

Histopathological effects of acute exposure to chlorine gas on Sprague-Dawley rat lungs.

It is now recognized that acute inhalational exposure to irritant gases such as chlorine can cause an asthma-like abnormality known as reactive airways dysfunction syndrome (RADS). The aim of this study was to evaluate the effects of exposure to various levels of chlorine on airway mucosa and lung parenchyma in an attempt to develop an animal model of this syndrome. Seventy-four Sprague-Dawley rats were exposed to air (controls) or to 50, 100, 200, 500, and 1500 ppm of chlorine for 2 to 10 min. Histological assessment was performed at 1, 3, 6, 12, 24, and 72 h after exposure. The results show that exposure to low concentrations (500 ppm) did not induce significant histological changes. Exposure to 1500 ppm for 2 min induced perivascular edema and the appearance of focal mild inflammation, whereas exposure to the same concentration for 10 min caused profound histological changes, including (1) 1 h: airspace and interstitial edema associated with bronchial epithelial sloughing; (2) 6 to 24 h: decreased edema and the appearance of mucosal polymorphonuclear leukocytes, maximal at 12 h; (3) 72 h: epithelial regeneration, manifested by hyperplasia and goblet cell metaplasia. We conclude that acute exposure to chlorine at a concentration of 1500 ppm for 10 min induces significant airway mucosal abnormalities that vary over a short period of time. Whether these abnormalities are related to the subsequent development of RADS awaits further experiments.

Animals↗

Distribution, retention, and fate of 2-aminoanthracene in rats after inhalation.

The distribution, retention, and fate of 2[3H]aminoanthracene (2-AA) were determined in male Fischer-344 rats after inhalation exposure (70 micrograms/liter; activity mass median diameter = 2.1 micron) for 30 min. Radioactivity was found in the turbinates, trachea, lungs, liver, kidneys, and gastrointestinal tract 20 min after exposure. Lower quantities of radioactivity were found in fat, brain, testes, and muscle. Inhaled 2-AA was excreted predominantly in feces (80%). The remaining 2-AA was excreted in urine. Organic soluble radioactivity was released from urinary conjugates after treatment of urine with acid and with beta-glucuronidase. This result suggests that glucuronides of both ring- and N-hydroxy-2-AA were excreted. The remaining radioactivity was water soluble and accounted for approximately one-half of the total urinary radioactivity. The organic soluble radioactivity found after hydrolysis indicated that inhaled 2-AA is extensively metabolized by rats after inhalation and excreted as conjugated metabolites. Eighty-three percent of orally administered material was absorbed into the body from the GI tract; thus, material cleared by mucociliary action after inhalation would contribute to total body burden. 2-AA, a nitrogen substituted polycyclic aromatic hydrocarbon (PAH), was very similar to other PAHs in its rapid distribution throughout the body and in its route of excretion after inhalation.

Administration, Oral↗

Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats.

Inhalation exposure experiments with the direct-acting alkylating agent epichlorohydrin (ECH) were done on noninbred male Sprague-Dawley rats. Single 6-hour exposure to ECH and follow-up for 14 days showed the median lethal concentration to be about 360 ppm. Further inhalation experiments were done with 6-hour exposure 5 days/week. A short-term 30-exposure regimen with 100 ppm ECH produced malignant squamous cell carcinomas of the nasal cavity in 15 of 140 rats and respiratory tract papillomas in 3 rats. Among 100 rats, lifetime exposure to 30 ppm yielded 1 malignant squamous carcinoma of the nasal cavity plus 1 nasal papilloma. No nasal or respiratory tract tumors were produced by lifetime exposure of 100 rats to 10 ppm. As controls, 100 air-treated and 50 untreated rats were used. A dose-rate effect was observed for ECH inasmuch as 30-day exposure to 100 ppm (3,000 ppm-days) produced 15 cancers in comparison to the 1 cancer from the lifetime exposure to 30 ppm (8,700 ppm-days) and no cancers from lifetime exposure to 10 ppm (2,500 ppm-days).

Animals↗

Withdrawal of inhaled nitric oxide from nonresponders after short exposure.

INTRODUCTION: Inhaled nitric oxide has been approved by FDA for treatment of hypoxic respiratory failure in term and near-term neonates. The safety of withdrawing NO in patients who fail to respond is a major concern. OBJECTIVE: To obtain further insight into the safety of withdrawing NO in patients who do not initially respond to this therapy, the charts of patients enrolled at our center in the Neonatal Nitric Oxide Study (NINOS) were reviewed. Oxygenation indices (OI) before, during and after exposure to NO or placebo were compared. METHODS: The charts of 110 neonates who received NO or placebo within the NINOS trial guidelines from 1995 to 1999 were reviewed. Arterial blood gases of nonresponders before, during and after a 30-minute exposure to different doses of NO or placebo were analyzed. RESULTS: For both high-dose and 20 ppm nonresponders who received NO, there was no significant change in OI from baseline after withdrawing NO. For patients receiving placebo, there was a significant increase in OI following a 30-minute exposure to placebo. CONCLUSIONS: NO has been shown to be effective in the treatment of neonatal respiratory failure; however, not all recipients demonstrate clinical improvement. This study showed that withdrawing NO in nonresponders did not cause increased respiratory morbidity when NO exposure was limited to 30 min. Differences between our results and others showing refractory hypoxia after withdrawing NO may be due to different durations of NO exposure and, possibly, its effect on endogenous NO metabolism.

Administration, Inhalation↗

Reactive airways dysfunction syndrome in housewives due to a bleach-hydrochloric acid mixture.

The sudden onset of asthmalike symptoms and persistence of airway reactivity following an acute exposure to an irritant gas or vapor has been termed reactive airways dysfunction syndrome (RADS). A mixture of sodium hypochlorite (bleach, 40%) and hydrochloric acid (18%) is commonly used as a household cleaning solution in our region. From this mixture, chlorine gas is produced, which can cause airway damage and ensuing RADS. Here we describe findings of patients with RADS due to this cleaning mixture, and determine factors associated with a favorable outcome. Data were collected retrospectively on 55 symptomatic patients presenting to our emergency department after inhalation exposure to a mixture of bleach and hydrochloric acid. Symptoms, past medical and smoking history, details of the exposure, initial peak expiratory flow rate (PEFR) and oxygenation, and acute reversibility of airways obstruction were documented. All patients met previously defined criteria for the diagnosis of RADS, but did not undergo methacholine challenge testing and bronchoalveolar lavage or histopathologic study. Fifty patients were followed over the course of 3 mo. The majority of exposures (64%) occurred in the bathroom or kitchen. Only 21 of 55 (38%) patients showed an improvement in PEFR of 15% or greater following two beta(2)-agonist inhalation treatments. In follow-up, 48 patients (87%) improved clinically and functionally (FEV(1)). Seven patients (13%) deteriorated, with ARDS developing in two, one of whom died from respiratory failure. Advanced age, initial low PEFR, exposure in a small enclosed area, use immediately after mixing, and prolonged short- and long-term exposures were associated with a poorer prognosis. This descriptive study is the largest case series in the literature of RADS developing after exposure to a bleach-hydrochloric acid mixture. The optimum acute treatment and long-term outcomes for patients with RADS due to this combination still need to be determined.

Accidents, Home↗