Respiratory Tract Irritation Research Articles

The Ferguson Principle and an Analysis of Biological Activity of Gases and Vapors

The Ferguson principle, thatPnar/PO(Pnaris the partial pressure of a series of compounds giving rise to a particular effect on a given system by a physical mechanism, andPOis the saturated vapor pressure of the liquid narcotic) is constant for a series of nonreactive narcotics or toxicants in a given system, is examined and shown to have no thermodynamic basis, contrary to the position of Brink and Posternak. Conditions under whichPnar/POmight be expected to be roughly constant, as an empirical observation, are set out and it is shown that such an observation is consistent with a receptor area in which the liquid narcotic solubilities are roughly constant. An interpretation of relationships between agonist descriptors and biological effects is carried out with three simple biological models. It is shown that the biological potency of nonreactive gases and vapors can be controlled either by an equilibrium between the agonist in the gas phase and the agonist in a receptor or by an equilibrium between the agonist in the gas phase and the agonist in a receptor phase. It is further shown that with the solvation equation of Abraham, solvents can be chosen that mimic the chemical properties of the receptor or receptor phase. For the example of upper respiratory tract irritation of male Swiss OF1mice, such solvents includeN‐formylmorpholine, a trialkylphosphate, and wet octanol, but not water itself.

Evaluation of chronic neurological sequelae after acute pesticide exposure using spect brain scans

A case in which SPECT brain imaging was used in the diagnosis and treatment of chronic effects from acute acetylcholinesterase inhibitor poisoning is presented. The patient was exposed to an insecticide mixture containing phosphorothiate, pyrethrin, piperonyl butoxide, and petroleum distillates, which produced symptoms consistent with acute acetylcholinesterase inhibitor poisoning as well as an upper respiratory tract irritant. Delayed sequelae of gross neurologic symptoms followed, that is, coarse tremor, intermittent hemiballistic movements of the right arm and leg, flaccid muscular tone, fasciculations of muscle groups, muscle cramps, and sensory disturbances. A brain single-photon emission computerized tomography (SPECT) scan was performed 34 mo postexposure, revealing significantly decreased blood flow to the left temporal lobe and to the right and left basal ganglia. The patient's paresthesias were treated with phenytoin, which resulted in worsening of her movement disorder. A trial of amantadine and selegiline (Deprenyl) resulted in a dramatic reduction in dysfunctional movements and ataxia. Post amantadine and selegiline therapy, brain SPECT images revealed significantly improved blood flow with minimally decreased blood flow to the right and left basal ganglia. The use of SPECT scan techniques helped to elucidate objective chronic central nervous system effects subsequent to an acute insecticide exposure and also assisted in the evaluation of the effectiveness of therapeutic intervention.

Sick building syndrome in a Canadian office complex.

A comprehensive questionnaire survey with limited environmental measurements was undertaken in a large sealed office complex where health complaints had been made by employees since the complex was first occupied. Most respondents suffered from upper respiratory tract irritation, eye and skin irritation, and many less specific complaints. Symptoms started shortly after first employment, were troublesome only at work, and persisted at other work locations within the complex. Employees who worked in cubicles tended to complain more than those who worked in open areas or closed offices; however, evidence of less than optimal ventilation, temperature, and humidity correlated poorly with symptom prevalence. The building was designed and ventilated for open-plan use; later partition into offices and cubicles appeared to aggravate the situation. Although concern about pregnancy outcome was expressed by women who conceived while employed at the complex, rates of spontaneous abortion and fetal defect were close to expectation.

Organochlorine ingestion

ABSTRACTA 48 year old man rapidly deteriorated and died following the intentional ingestion of a commercial pesticide mixture containing chlordane and dichloroethyl ether with kerosene as the solvent vehicle.After oral ingestion, chlordane is primarily a neurotoxin. Dichloroethyl ether is a respiratory tract irritant. Both have effects on several other systems. Kerosene is a potent cause of aspiration pneumonitis when inhaled and gastric emptying is not recommended unless it is the vehicle for other, more toxic substances, as in this case.Management for both chlordane and dichloroethyl ether ingestion is supportive, involving airway maintenance, decontamination, and gastric lavage and charcoal administration.

Inhalation toxicity of 1,6-Hexanediamine dihydrochloride in F344/N rats and B6C3F 1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Sensory irritation of the upper respiratory tract.

Sensory irritation of the upper respiratory tract.

The sick building syndrome. I. Definition and epidemiological considerations.

It has been difficult to confirm that a given building is responsible for allergic symptomatology, exacerbation of asthma, or immunological dysfunction. In fact, in most studies, few objective immunological parameters have been studied and only rarely has there been any quantitation of IgE or secondary mediators. Furthermore, although many studies deal with rhinitis or respiratory tract irritation, there is a misconception that all such symptoms are allergic in nature, and studies attempting to prove that allergies are caused by buildings frequently neglect to prove that these are indeed true allergic responses. In addition, many of the symptoms that people attribute to sick building syndrome (SBS) or building-related illness, such as headaches, dizziness, fatigue, nausea, cough, and eye irritation, are subjective, and studies often fail to take into account other possible causes that may be inherent in the subjects, such as sinusitis, hyperventilation syndrome, or psychosomatic illness. Unfortunately, most clinical studies on SBS pay little attention to the preexisting conditions that a subject may have and discount the possibility that the inciting agent does not cause symptoms, but merely exacerbates a preexisting condition. Moreover, they offer no information about the nature of the mechanisms of action or pathophysiological relationships. Clearly, further studies are necessary to further explain the complexity of complaints that currently exist. Indeed, SBS might properly be paraphrased as "what is it?--if it is!"

Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts.

A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment.

Recent developments in understanding the toxicity of PTFE thermal decomposition products

AbstractFluropolymers, especially polytetrafluoroethylene (PTFE), have good fire‐resistance properties, but their application is limited by concerns over the toxicity of their thermal decomposition products. In experiments using a tube furnace system similar to the DIN 53 436 method, the 30‐minute (+ 14 days observation) LC50 in mass loss terms was found to be 2.9 mgI−1 (Standard Error 0.40) under non‐flaming conditions, approximately ten times as toxic as wood and most other materials. Toxicity was due to upper respiratory tract and airway irritation, and was consistent with the known effects of carbonyl fluoride and hydrogen fluoride. When decomposed in the NBS cup furnace test under‐non‐flaming conditions, PTFE evolved extreme‐toxicity products with an LC50 of approximately 0.05 mgI−1 (mass loss), approximately 1000 times as toxic as wood and most other materials. Toxicity was due to deep lung irritation and oedema. Investigations of the range of conditions under which the extreme toxicity of PTFE products occurs in both small‐scale (200‐litre) and intermediate‐scale (6 m3) experiments have shown that the highest toxicity occurs when PTFE is decomposed under non‐flaming conditions over a temperature range of 400–650°C, and when the primary decomposition products are subjected to continuous secondary heating. At higher or lower temperatures, when the sample is flaming, when decomposition products from wood are also present in the chamber, when secondary heating is curtailed, or when the molecule contains hydrogen as well as fluorine, the toxicity of the products is greatly reduced, tending towards the region of ten times the potency of most other materials. Extreme toxicity is associated with a particulate, but the particulate atmosphere is not always extremely toxic, the potency decreasing as the fumes age.

Measuring exposure for the epidemiologic study of acute effects.

This report explores the importance of characterizing short-term (peak) exposures for successful epidemiologic study of acute reversible effects. By selecting upper respiratory tract irritation, which is time-limited, reversible, and not critically affected by host factor sensitivities, the illustrated approach (directed at an acute respiratory irritant) provides insights on issues important in the general study of acute effects. The fundamental concern in a study of acute irritant effects is that such events occur in response to abrupt increases in exposure. This calls for a closer examination of how to distinguish bursts, or peaks, of exposure from continuous exposures measured simply as time weighted averages. Three parameters of peak exposures are discussed: duration, magnitude, and frequency. The importance of duration is illustrated by contrasting exposure patterns relevant for the study of acute vs. chronic health effects. The minimum magnitude of a peak relevant to the study of a specific physiologic response requires knowledge of the threshold below which no detectable response occurs. For any identified threshold level, only exposures exceeding that level are defined as relevant peaks for an exposure-response analysis. Finally, the issue of frequency, the minimum length of time between successive exposures necessary for the subject to return to baseline risk, is explored. A study of respiratory irritation associated with sodium borates is used to illustrate these issues.

Factors influencing indoor air quality in Hong Kong: Measurements in offices and shops

Abstract Comparisons of levels of respirable suspended particulates, carbon monoxide, carbon dioxide, nitrogen dioxide, volatile organic compounds and nicotine have been made between indoor and outdoor air in 35 street‐level shops and 35 offices in Hong Kong. Additionally, counts of bacteria and fungi were made indoors. In shops, the study showed that the air quality was principally determined by outdoor air, with highly significant correlations between indoor and outdoor levels of RSP, CO and NO2. The levels of these substances were significantly lower in offices. Measurement of analytes related to tobacco smoking showed extremely low levels of environmental tobacco smoke in both shops and offices, but the overall numbers of smokers in such establishments was small. For offices, occupier complaints regarding drowsiness, headache and symptoms of eye, nose and respiratory tract irritation were positively associated with CO2 levels. NO2, CO, toluene and benzene levels did not show any relationship to occupi...

Sick-Hospital Syndrome

An outbreak of complaints consisting primarily of eye and respiratory tract irritation accompanied by headache, dizziness, fatigue, and nausea occurred among the operating room personnel of a large metropolitan hospital. This initially was attributed to infiltration of diesel exhaust emissions into the ventilation system. However, following correction of this problem and subsequent unrevealing air monitoring, symptoms persisted and were noted in personnel in adjacent areas of the hospital as well. An industrial hygiene and medical evaluation was undertaken. Monitoring for carbon monoxide, formaldehyde, and anesthetic gases and review of medical records and patient examinations were unrevealing, and the problem resolved gradually over several weeks. This outbreak represents a case of building-associated illness among health professionals in a hospital setting that was triggered by a single, identifiable noxious exposure but was sustained despite any apparent ongoing noxious exposures.

DERMAL SENSITIZATION POTENTIAL AND INHALATION TOXICOLOGICAL EVALUATION OF 4-PHENYLCYCLOHEXENE

4-Phenylcyclohexene (4-PCH) is a by-product formed in trace amounts during the production of styrene-butadiene latexes, which are used in carpet manufacturing. The dermal sensitization potential of 4-PCH was evaluated by using a modification of the Buehler method. The condition of the test site was evaluated 24 and 48 hr after the challenge application with no response observed in any of the guinea pigs. For the acute inhalation study, groups of five Fischer 344 rats/sex were exposed to 16 or 60 ppm 4-PCH for a single 6-hr exposure. Subsequently, groups of 10 Fischer 344 rats/sex were exposed to time-weighted average concentrations of 0, 1, 10, or 50 ppm (0, 6.6, 65, or 320 mg/m3) 4-PCH for 6 hr/day, 5 days/week for nine exposures. The highest vapor concentration, 50 ppm, was the maximum attainable during the course of the 2-week study. It was only achieved by acclimating the chamber with saturated vapor prior to each animal exposure. The following parameters were evaluated for the 2-week study: clinical signs, body weights, selected organ weights, hematology, clinical chemistry, urinalysis, and histopathology. All rats survived to the termination of the study and had no clinical or pathologic evidence of eye, skin, nasal, or respiratory tract irritation. There were no exposure-related effects identified in any of the parameters monitored. Thus, 4-PCH produced no toxicity at the highest concentration that could be generated and did not produce delayed contact hypersensitivity in guinea pigs.

Human Nail Dust: Hazard to Chiropodists or merely Nuisance?

This survey was carried out in response to anxiety among chiropodists as earlier reports had raised the possibility of respiratory damage as a result of sensitization to trichophytons. Questionnaires were sent to 327 chiropodists and 168 replies were received. The aim was to investigate respiratory symptoms and their relationship to work and drill usage. All of those completing questionnaires were invited to attend the occupational health department for prick tests and lung function tests. Just over one half of those who were invited attended. Although upper respiratory symptoms were common, only eye symptoms and wheeze were significantly more prevalent in those who used non-vacuum drills. Nasal symptoms were commoner in those who had spent less than ten years in the profession. Throat symptoms and multiple symptoms occurred more commonly in the 17 per cent of attenders who had positive prick tests to trichophytons. There were no cases of occupational asthma and no definite relationship between any symptom and work. It was confirmed that sensitization to trichophytons was common (16.5 per cent) but did not produce chest problems. Nail dust might produce symptoms by simple irritation of the upper respiratory tract.

Sick Building Syndrome: Acute Illness among Office Workers—The Role of Building Ventilation, Airborne Contaminants and Work Stress

Outbreaks of acute illness among office workers have been reported with increasing frequency during the past 10-15 years. In the majority of cases, hazardous levels of airborne contaminants have not been found. Generally, health complaints have involved mucous membrane and respiratory tract irritation and nonspecific symptoms such as headache and fatigue. Except for rare examples of hypersensitivity pneumonitis related to microbiologic antigens, there have been no reports of serious morbidity or permanent sequelae. However, the anxiety, lost work time, decreased productivity and resources spent in investigating complaints has been substantial. NIOSH has reported on 446 Health Hazards Evaluations that were done in response to indoor air complaints. This data base is the source of most of the published accounts of building-related illness. Their results are summarized here with a discussion of common pollutants (tobacco smoke, formaldehyde, other organic volatiles), and the limitations of the available industrial hygiene and epidemiologic data. There has been one large scale epidemiologic survey of symptoms among office workers. The results associate risk of symptoms to building design and characteristics of the heating/air-conditioning systems, consistent with the NIOSH experience. Building construction since the 1970s has utilized energy conservation measures such as improved insulation, reduced air exchange, and construction without opening windows. These buildings are considered "airtight" and are commonly involved in episodes of building-associated illness in which no specific etiologic agent can be identified. After increasing the percentage of air exchange or correcting specific deficiencies found in the heating/air-conditioning systems, the health complaints often resolve, hence, the term "tight building syndrome" or "sick building syndrome."(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrogen Bonding 12. A New QSAR for Upper Respiratory Tract Irritation by Airborne Chemicals in Mice

AbstractUpper respiratory tract irritation of male Swiss OF1 mice by airborne chemicals is well correlated by the following equations for the toxicity of nonreactive compounds, magnified image FRD′50 is the concentration in mol 1−1 of the airborne chemical required to elicit a 50% decrease in respiratory rate, and the explanatory variables are δ2 a polarisability correction term, π the solute dipolarity, α the solute hydrogen‐bond acidity, Vx the characteristic volume, and L16 the gas/hexadecane partition coefficient. These equations considerably resemble corresponding equations for gas/liquid partition coefficients into organic bases such as tricresylphosphate, but do not resemble an equation for gas/water partition coefficients.

Health Problems among Spice Grinders

Sixty-one male spice grinders from 14 factories were studied to determine if they had any skin problems, respiratory symptoms or hearing loss associated with their work. All subjects were interviewed and examined. Audiometric examinations were arranged for those with significant noise exposure. Assessments of dust and noise levels were conducted. Symptoms of upper respiratory tract irritation, such as sneezing and runny nose, during work were experienced by 49.2 per cent of workers. These symptoms were maximal in the first few weeks of employment in spice grinding and did not recur in half of the affected workers. Over 26 per cent of the workers experienced a warm or burning sensation of the skin when grinding chili or pepper. None of the spice grinders had symptoms or evidence on physical examination of allergic skin disease or asthma. Noise-induced hearing loss was detected in 21 per cent of the workers examined but none had severe disabling deafness. Dust levels ranged from 0.03 to 0.82 mg/m3, with a mean value of 0.15 mg/m3. Noise exposure was significant, with levels of between 87 and 98 dBA. Control measures to reduce the noise and dust exposure are discussed.

Epistaxis Due to Glutaraldehyde Exposure

Glutaraldehyde is commonly used as a cold disinfecting agent in the hospital setting and may cause irritation of skin, mucous membranes, and the upper respiratory tract in exposed workers. We report an unusual case of recurrent epistaxis associated with other symptoms of upper respiratory tract irritation and skin rash in a hospital employee using glutaraldehyde for sterilization of endoscopy equipment. A visit to the workplace revealed inadequate personal protective measures and inadequate local ventilation. High-risk work practices contributing to the hazard included soaking of endoscopy equipment in uncovered basins, manual pouring of concentrated glutaraldehyde solutions without the use of proper protective measures, and the use of paper masks, which provide inadequate protection from solvent vapors. The patient's symptoms resolved with the implementation of personal protective measures and engineering controls.

Pyrethrin poisoning from commercial-strength flea and tick spray

A case of acute poisoning followed inhalation and cutaneous exposure to an over-the-counter flea and tick insecticide containing 0.15% pyrethrins. A self-limited syndrome of cutaneous paresthesias, upper respiratory tract irritation, dyspnea with productive cough, and repetive vomiting and diarrhea occurred. The patient recovered uneventfully with conservative therapy. A review of the pharmacology and toxicity of pyrethrins and related products is discussed, as well as management of pyrethrin poisoning.

Effect of cadmium chloride on thyroid activity of the female Indian palm squirrel, Funambulus pennanti (Wroughton).

In humans, exposure to Cadmium (Cd) occurs primarily through inhalation and ingestion. Acute Cd inhalation results in pulmonary edema and respiratory tract irritation; while chronic inhalation causes fibrotic and emphysematous changes in lung tissue as well as damage of renal proximal tubules. Several workers have reviewed the toxic effects of Cd on mammals, including man. In laboratory animals Cd produced kidney damage, testicular necrosis and atrophy, brain hemorrhage, hypertension, liver damage and reduced growth. It also induced changes in the adrenal and thyroid gland in the rat. In this study, squirrels, Funambulus pennanti, were administered a single dose of CdCl/sub 2/ intraperitoneally, and their thyroid structure and radioiodine I/sup 131/ uptake were assessed.