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At least 145 records · Page 8Linked to original sources
PubMed2000

Isocyanate exposure and occupational asthma: a case-referent study.

OBJECTIVE: To examine the quantitative relation between exposure to isocyanates and occupational asthma, and to explore the role of atopy and smoking in occurrence of the disease. METHOD: A case-referent study was undertaken of cases from two manufacturing companies (A and B) from which referents without disease could be selected and reliable exposure measurements were available. In company A, 27 cases mainly attributed to toluene diisocyanate (TDI) were matched to 51 referents on work area, start and duration of employment, sex, and age. Exposures were estimated from existing measurements by job category. In company B there were seven cases attributed to 4,4'-diphenylmethane diisocyanate (MDI) in two areas of the plant; 12 non-cases from the same areas were used as referents. Personal exposure measurements were available for all cases and 11 referents. RESULTS: No difference in peak exposures between cases and referents was found in either plant; but in both, time weighted average (TWA) exposures at the time of onset of asthma were higher for cases. In A, the mean TWA exposure for cases was 1.5 (95% confidence interval (95% CI) 1.2 to 1.8) ppb compared with 1.2 (1.0 to 1.4) ppb for referents. From a matched analysis, the odds ratio (OR) associated with 8 hour TWA exposure to isocyanates greater than 1.125 ppb (the median concentration for the referent group) was 3.2 (95% CI 0.96 to 10.6; p=0.06). Occupational asthma was associated with a pre-employment history of atopic illness (OR 3. 5, p=0.04) and, less strongly, with smoking (OR 2.1, p=0.14). In B, small numbers limited analysis, but three of seven cases had at least one TWA exposure measurement greater than 5 ppb compared with one of 11 referents (OR 7.5, p=0.09). CONCLUSION: Asthma can occur at low concentrations of isocyanates, but even at low concentrations, the higher the exposure the greater the risk. By contrast with other studies, smoking and atopy seemed to increase the odds of occupational asthma due to isocyanates, but did not affect the estimate of risk associated with exposure.

Adolescent↗
PubMed1990

Immunologic hemorrhagic pneumonia caused by isocyanates.

The occurrence of hemoptysis, dyspnea, and bilateral pulmonary opacities progressed to respiratory failure in a 34-yr-old man. Recovery occurred with corticosteroid therapy. In the absence of evidence for an infectious etiology, the possibility of immunologic trimellitic anhydride (TMA) hemorrhagic pneumonitis was considered when the lung biopsy excluded Goodpasture's and other diseases and because the patient was a spray painter. Serologic evaluation for antibodies against TMA was requested. Because the immunologic studies for TMA were negative, and because the patient was a spray painter, immunoassays for three isocyanates conjugated to human serum albumin (HSA) were carried out although there was no specific history of isocyanate exposure at that time. High levels of IgG and IgE antibodies were detected against hexamethylene diisocyanate (HDI)-HSA and toluene diisocyanate (TDI)-HSA. Further investigation documented exposure to spray paint that contained HDI and another isocyanate. The paint was sprayed on warm metal, and subsequently the worker developed an acute illness. Further plant studies were not possible. We propose that the pathogenesis of this case of hemorrhagic pneumonitis is immunologic because of uncontrolled exposure to HDI and TDI, is analogous to the immunologic hemorrhagic pneumonia caused by TMA, and should be considered as a possible cause of a similar acute lung disease after isocyanate exposure.

Acute Disease↗
PubMed2000

Inadvertent topical exposure to isocyanates caused damage to the entire eyeball.

Isocyanates are part of a group of important chemicals necessary in the production of adhesives, synthetic rubbers, and a variety of plastics. They are known to have minimal toxic effects when administered locally. However, we experienced a case of damage involving the entire eyeball in a person who accidentally exposed his eye to isocyanates. The patient presented with inflamed conjunctiva, and shrunken cornea and sclera, with focal atrophic changes in the iris. The lens and vitreous were opacified. After removal of the lens and vitreous, there were large areas of atrophic retina and areas of retinal necrosis with holes. We found that locally absorbed isocyanates can cause damage to the entire eyeball. Therefore, we recommend that if there is any evidence of isocyanate penetration, early vitrectomy should be performed to help in determining the extent of retina damage and to decrease the amount of toxic substance in the vitreous.

Accidents, Occupational↗
PubMed1999

[Pathologic mechanisms of diseases caused by isocyanates--review of current knowledge].

During recent years in industrial countries, isocyanates have been one of the main causes of occupational asthma. The mechanisms of isocyanate-induced disorders are still unknown but recent evidence suggests immunological reactions, including cell-mediated immune responses. Immune responses to isocyanates may result in different illnesses, some of which represent cell- and/or antibody-mediated entities. In addition, irritative, toxic, and mutagenic effects may occur. This review summarizes current knowledge of the pathomechanisms, including immunological and nonimmunological (genotoxic and mutagenic) aspects of isocyanate disorders.

Animals↗
PubMed1999

[Occupational asthma due to isocyanates: a study of 21 patients].

BACKGROUND: A descriptive-evolutive study of a series of patients diagnosed with bronchial occupational asthma due to isocyanate exposure. SUBJECTS AND METHODS: Retrospective study of 21 patients diagnosed with bronchial occupational asthma due to isocyanates. Family story, clinical data, functional respiratory study, allergic and laboratory tests were collected. Clinical and functional performance one year after diagnosis was evaluated in patients who had and who had not stopped causal exposure. RESULTS: 17 men and 4 women aged 22 to 59 years were evaluated. In 5 cases (23.8%) family story of atopy was documented and 12 (57.14%) patients were smokers. Seven out of 21 patients were exposed to paint related products at work being this the most common reason. Average time (SD) from the beginning of exposure to development of symptoms was 16.10 (22.5) months. IgE levels were high in 6 (28.57%) and specific IgE to isocyanates was high in 8 (38%), in all cases bronchial hyperreactivity was detected. In 18 patients (85.7%), the study of maxim expiratory flow (MEF) register demonstrated occupational asthma while in the remaining 3 patients a provocation test was performed with positive result. In the annual follow up visit, the 17 patients who avoided casual exposure showed clinical improvement, 7 of them also with functional improvement while in the remaining 10 patients no significant functional change was observed. On the other hand, 3 of the 4 patients who, although protected, underwent exposure, became clinical and functionally worse (p = 0.003, Fisher test). CONCLUSIONS: The etiology of occupational asthma due to isocyanates is not often assessed and usually lately diagnosed. This aspect is worth considering as the illness prognosis seems related to casual agent avoidance.

Adult↗
PubMedDate not supplied

[Course of isocyanate-induced asthma in relation to exposure cessation: longitudinal study of 50 subjects].

Isocyanates, particularly Toluene Diisocyanate (TDI), have been the most common cause of occupational asthma for decades. Fifty workers with a diagnosis of isocyanate-induced asthma were followed up for a mean period of 8.4 years. Pulmonary function testing for FVC and FEV1, allergological tests, nonspecific bronchial challenge to methacholine and specific bronchial challenge to isocyanates were performed at the time of diagnosis and during follow-up. Data on symptoms and drug response were rated on a scale. Patients were subdivided into two groups based on persistence of (A; 13 patients) or removal from (B; 37 patients) isocyanate exposure. There were no significant differences in any characteristic between the two groups at the time of diagnosis. At follow-up, group B subjects showed significant improvement in symptoms, consequent reduction in use of medications and increase in PD20. None worsened, sixteen (43.3%) remained stable, twelve (32.4%) improved and nine (24.3%) became asymptomatic. The latter subjects were generally younger, they had shorter duration of symptoms and exposure to the agents, and longer removal from exposure, although none of these differences was significant. In 67% of cases they had an immediate reaction to TDI challenge. By contrast, the condition of group A patients deteriorated significantly during the follow-up period in terms of symptoms, pulmonary function parameters, PD20 and use of medications. Overall, seven subjects (53.8%) worsened during follow-up and none improved. Group B subjects were further divided into subgroups B1 and B2 based on duration of removal from exposure: B1 < 10 years, B2 > or = 10 years. There were no significant differences between the two subgroups, even though PD20 was higher in B2. The present study confirms that early diagnosis and immediate removal from exposure are crucial, though not always sufficient, for a favourable evolution of the disease.

Adult↗
PubMed2002

[Asthma caused by isocyanate exposure].

Asthma from exposure to inhalation of isocyanates is an affection recognised under the title of work place diseases within table no 62 in the General Regulations and no 43 in the Agricultural Regulations. If workplace induced asthma is the most frequent of the workplace respiratory illnesses with a frequency of 2 to 15% of the asthmatic population, 1 patient in 2 will only be the object of a declaration and 1 in 3 the objective of a survey by the administrative authorities. The frequency of isocyanate asthma is on average 16.4% amongst workplace asthmas (19.6% in the industrial environment and 1.5% in an agricultural environment); if this prevalence is dose-dependent according to Baür, 30% of patients exposed to weak doses of isocyanate (0.3% ppb according to White) develop asthmatic disease whilst Bernstein estimates as 5 to 10% the frequency of asthmatic disease per 100,000 persons who are exposed to isocyanates.

Adult↗
PubMed2003

[Pneumopathy due to isocyanate hypersensitivity: recognition as an occupational disease].

INTRODUCTION: Hypersensitivity pneumopathies (HSP) are listed as number 66 in the list of occupational diseases but this list includes regulatory requirements that are not applicable to isocyanates. The authors report the case of a worker exposed to isophane di-isocyanate (IPDI) during the manufacture of polyurethane foam. CASE REPORT: The diagnosis of HSP was based on the clinical presentation (dyspnoea, fever, crepitant rales) and the complimentary investigations (ground glass appearance on the thoracic CT scan, lymphocytosis in the broncho-alveolar lavage). It was confirmed by trans-bronchial biopsy. Only the functional assessment (airflow obstruction and absence of marked reduction in CO transfer) was atypical. With regard to the role of isocyanates the number of published cases (49 since the first observation in 1976) shows that this aetiology is rare. In the case presented the chronology of symptoms (regression following exclusion and immediate relapse following re-exposure) and the absence of exposure to other agents known to cause HSP confirm the aetiology with near certainty. This case was recognised within the framework of the complimentary procedure that allows for unlisted diseases. CONCLUSION: In order to assist the management and recognition of HSP due to isocyanates there is good reason to raise the awareness of the medical profession and to extend the list of occupational diseases.

Alveolitis, Extrinsic Allergic↗
PubMed1994

Effect of carbamate thioester derivatives of methyl- and 2-chloroethyl isocyanate on glutathione levels and glutathione reductase activity in isolated rat hepatocytes.

The present study examined the effects of S-(N-methylcarbamoyl)glutathione (SMG), S-(N-methylcarbamoyl)-L-cysteine (L-SMC) and some analogs of these S-linked conjugates of methyl isocyanate (MIC) on the activity of glutathione reductase (GR) in freshly isolated rat hepatocytes and on the levels of reduced and oxidized glutathione (GSH and GSSG) in exposed cells. Both SMG and its monoethyl ester (0.5 mM) were found to inhibit GR weakly, although L-SMC proved to be an effective inhibitor of the enzyme (60 +/- 4% activity remaining after a 4-hr incubation at 0.5 mM). The cysteine adduct (SCC) of 2-chloroethyl isocyanate (CEIC) was a strong inhibitor of GR (27 +/- 1% activity remaining after a 1-hr incubation at 0.1 mM) and was essentially equipotent with the antitumor agent N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU). L-SMC depleted intracellular GSH in a time- and concentration-dependent manner up to 2 hr of incubation, beyond which time GSH levels began to recover. Exposure of cells to the enantiomeric conjugate, D-SMC, led to a similar concentration- and time-dependent inhibition of GR and fall in intracellular GSH, but in this case the depletion of GSH was extensive and was sustained throughout the 5-hr incubation period. Only a small amount (less than 10%) of the GSH that was lost from cells exposed to SMC was recovered in the medium, indicating that SMC did not cause efflux of GSH (most of the free cysteine released during breakdown of SMC was recovered in the medium). Experiments with hepatocytes exposed for 5 hr to SCC (0.1 mM) demonstrated that GSSG levels were elevated by 32 +/- 5% relative to controls. Collectively, these results indicate that carbamate thioester conjugates of MIC and CEIC inhibit GR, probably via release of the free isocyanate at the cell surface, which then penetrates the hepatocyte. The inhibitory effects of the isocyanates on GR, coupled with their propensity to react spontaneously with GSH, combine to deplete significantly intracellular stores of GSH.

Animals↗
PubMed1992

Activated T-lymphocytes and eosinophils in the bronchial mucosa in isocyanate-induced asthma.

We have studied the phenotype and activation status of leukocytes in the bronchial mucosa in patients with isocyanate-induced asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects with occupational (five toluene- and four methylene diisocyanate-sensitive) asthma, 10 subjects with extrinsic asthma, and 12 nonatopic healthy control subjects. Bronchial biopsy specimens were examined by immunohistology with a panel of monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase method. There was a significant increase in the number of CD25+ cells (interleukin-2 receptor-bearing cells, presumed "activated" T-lymphocytes; p less than 0.01) in isocyanate-induced asthma compared with that of control subjects. There were also significant increases in major basic protein (BMK-13)-positive (p less than 0.02) and EG2-positive (p less than 0.01) cells that represent total and "activated" eosinophil cationic protein-secreting eosinophils, respectively. In agreement with our previous findings, CD25+ (p less than 0.01), BMK-13 (p less than 0.03), and EG2+ (p less than 0.01) cells were also elevated in extrinsic asthma. No significant differences were observed in the numbers of T-lymphocyte phenotypic markers (CD3, CD4, and CD8) between subjects with asthma (isocyanate-induced and extrinsic) and control subjects. Similarly, no significant differences in immunostaining for neutrophil elastase (neutrophils) or CD68 (macrophages) were observed. The results suggest that isocyanate-induced occupational asthma and atopic (extrinsic) asthma have a similar pattern of inflammatory cell infiltrate. The results support the view that T-lymphocyte activation and eosinophil recruitment may be important in asthma of diverse etiology.

Adult↗
PubMed1984

Preliminary evaluation of isocyanate-generating nitroheterocycles as chemosensitizers, radiosensitizers and hypoxic cell cytotoxic agents.

Nitro-compounds containing an acetylated acetohydroxamic acid side chain in the N-1 position of a 5-membered ring nitrogen heterocycle have been synthesized. These compounds, which can generate isocyanates via a Lossen rearrangement, were evaluated in order to test the hypothesis that they may be effective radiation and chemosensitizing agents by nature of their isocyanate-associated carbamoylating potential. Evaluation of one such compound, DJW-77 (1(O-Acetyl-Acetohydroxamic acid)-3-nitropyrazole) as a radiation sensitizer, chemosensitizer and hypoxic cell toxin is reported. In vitro DJW-77 demonstrates a potent selective cytotoxicity toward hypoxic EMT-6 tumor cells, is an effective potentiator of CCNU toxicity and is comparable to MISO with respect to its radiation-sensitizing potential. The activity of the drug is eliminated under aerobic conditions. To test the hypothesis that the activity of DJW-77 is related to isocyanate generation, the non-acetylated analog of DJW-77 (which does not directly undergo the Lossen rearrangement) and the parent 3-nitropyrazole ring structure were evaluated. Neither compound enhanced CCNU toxicity, and on an equimolar basis were inferior to DJW-77 as radiation sensitizers. While the non-acetylated analog was cytotoxic to hypoxic cells, relative to DJW-77 this activity was substantially reduced. These studies indicate that the addition of a side chain capable of generating an isocyanate can enhance the cytotoxicity and sensitizing activity of nitroheterocycles.

Animals↗
PubMed1998

The Alcoholysis Reaction of Isocyanates Giving Urethanes: Evidence for a Multimolecular Mechanism.

A kinetic and mechanistic investigation of the catalyzed alcoholysis of isocyanates was undertaken. Both experimental and theoretical results showed that the alcoholysis should be understood by a multimolecular intervention of the alcohols. The alcoholysis of isocyanate was examined experimentally for 2-propanol and cyclohexanol in low and high concentrations. It is suggested that either two or three molecules of the alcohol are implicated from the kinetic study, while the reaction with trimers becomes dominant at high alcohol concentrations. In accordance with these results, theoretical study suggests an active participation of at least three alcohol molecules in a reacting supersystem, giving rise to a genuine effect. The detailed reaction mechanism for the alcoholysis reaction by methanol and methanol clusters (HN=C=O + n(CH(3)OH), n = 1-3) was modeled by ab initio methods, both in the gas phase and in solution. The nucleophilic addition occurs in a concerted way across the N=C bond of the isocyanate rather than across the C=O, similar to the isocyanate hydrolysis. The bulk solvent effect, which is treated by a polarizable continuum model (PCM), does not affect the preference of the alcohol to attack across the N=C bond as pointed out by the gas-phase values.

Journal Article↗
PubMed1998

The in vivo effect of isocyanate-induced asthma on basophil histamine release.

In vitro studies have suggested that basophils are involved in the asthmatic response to isocyanate. Classified by the type of airway response, three groups of patients exposed to isocyanate were studied: 1) nonreactive (n=3), 2) immediate responders (n=4), and 3) late responders (n=4). Basophil histamine release to concanavalin A (conA), FMLP, and anti-IgE was evaluated before and during the airway response. Histamine release significantly (P=0.009 for conA and 0.03 for anti-IgE) increased after exposure to isocyanate only in the group which had late bronchial response. Additionally, good correlation was found between baseline FEV1/FVC% and degree of histamine release of basophils stimulated with conA. These findings support a role for basophils in the late asthmatic response to isocyanate.

Adult↗
PubMed1983

Amines: possible causative agents in the development of bronchial hyperreactivity in workers manufacturing polyurethanes from isocyanates.

Investigations of respiratory symptoms among workers in a factory producing polyurethane foam included measurement of air pollution with amines and isocyanates and a simultaneous health investigation of the exposed workers. An increased bronchial reactivity to inhaled methacholine was found in the study group compared with two unexposed control groups. This finding, together with visual disturbances in the exposed group, were assumed to be caused mainly by the volatile amines. The concentrations of isocyanates in air were well below 0.005 ppm. The amine concentration was 1000 to 10 000 times higher than the isocyanate concentration. The most volatile amine, N-methylmorpholine, occurred in the air in concentrations higher than 10 ppm. The results indicate that not only the isocyanates but also the amines might well be responsible for respiratory symptoms among exposed workers in polyurethane foam production.

Adult↗
PubMed1982

Studies on antigens useful for detection of IgE antibodies in isocyanate-sensitized workers.

Toluene diisocyanate was conjugated by two different methods to human serum albumin. These conjugates were used as antigens in the radio-allergo-sorbent-test (RAST) for detection of IgE antibodies in sera of isocyanate-sensitized persons. Chemical analyses have shown that conjugates containing 18-28 mol of isocyanate residues per mol protein were more potent antigens than those containing greater amounts of isocyanate residues. These results were confirmed by RAST inhibition experiments. The importance of optimization of the immunoradiometric methods for study of immunologic sensitization to isocyanates is discussed.

Antibodies↗
PubMed1991

[Asthma due to isocyanates in a theoretically non-exposed worker].

We report a case of isocyanate induced asthma in a patient who had been previously exposed to isocyanate and had become a porter in a factory producing polyurethene foam. The test for exposure to TDI was positive. The recognition of occupational asthma was nevertheless challenged and the patient was not considered to be carrying out work involving exposure to the inhalation of isocyanates. The effect of a change of job in the development of occupational asthma, and the risk of asthma induced by isocyanates despite inhaled concentrations inferior to the VME, the difficulty of obtaining a recognition of occupational asthma when the working conditions fulfilled do not exactly correspond to those labelled in the schedule for occupational diseases, are discussed in this paper.

Adult↗
PubMedDate not supplied

Facts and fallacies involved in the epidemiology of isocyanate asthma.

Personal experience and analysis of the medical literature on isocyanate asthma shows, that the reported incidence of this disease varies between 0 and 25%. Reasons for differences in observed incidence are intensity of isocyanate exposure, criteria for diagnosis, mode of calculation, sensitizing capacity of different isocyanates, individual predisposition and confounding factors (adjuvants). There is no geographical or ethnical prevalence. Work places at risk are those with isocyanate concentrations above 20 ppb (ceiling).

Asthma↗
PubMed1983

Inhibition of acetylcholinesterase from human erythrocytes by isocyanates.

Four isocyanates, two of which are widely used in industry, were found to be potent inhibitors of acetylcholinesterase from human erythrocytes. Aliphatic isocyanates are stronger inhibitors of the enzyme than are aromatic isocyanates. Incubation at 21 to 23 degrees C for several days leads to slow and limited spontaneous reactivation of the inhibited enzyme. This enzyme inhibition may be a contributing factor in the induction of respiratory disease observed in about 5% of workers exposed to isocyanate vapors.

Acetylcholinesterase↗