Susceptibility of the Bhopal-methyl isocyanate (MIC)-gas-tragedy survivors and their offspring to COVID-19: What we know, what we dont and what we should? / Suscetibilidade dos sobreviventes da tragédia de Bhopal-isocianato de metila (CIM)-gás e seus filhos ao COVID-19: O que sabemos, o que não sabemos e o que devemos?

Abstract There is credible evidence that the 1984-Bhopal-methyl isocyanate (MIC)-gas-exposed long-term survivors and their offspring born post-exposure are susceptible to infectious/communicable and non-communicable diseases. Bhopal's COVID-19 fatality rate suggests that the MIC-gas tragedy survivors are at higher risk, owing to a weakened immune system and co-morbidities. This situation emboldened us to ponder over what we know, what we don't, and what we should know about their susceptibility to COVID-19. This article aims at answering these three questions that emerge in the minds of public health officials concerning prevention strategies against COVID-19 and health promotion in the Bhopal MIC-affected population (BMAP). Our views and opinions presented in this article will draw attention to prevent and reduce the consequences of COVID-19 in BMAP. From the perspective of COVID-19 prophylaxis, the high-risk individuals from BMAP with co-morbidities need to be identified through a door-to-door visit to the severely gas-affected regions and advised to maintain good respiratory hygiene, regular intake of immune-boosting diet, and follow healthy lifestyle practices.

Resumo Há evidências plausíveis de que os sobreviventes a longo prazo da exposição a gás de 1984 e isocianato de metila (CIM), em Bhopal, e seus filhos nascidos após esse fato estão suscetíveis a doenças infecciosas/transmissíveis e não transmissíveis. A taxa de fatalidade COVID-19 de Bhopal sugere que os sobreviventes da tragédia do gás MIC estão em maior risco, devido a um sistema imunológico enfraquecido e comorbidades. Essa situação nos encorajou a refletir sobre o que sabemos, o que não sabemos e o que devemos saber sobre a suscetibilidade deles ao COVID-19. Este artigo objetiva responder a essas três perguntas que surgem na mente dos funcionários de saúde pública sobre estratégias de prevenção contra o COVID-19 e promoção da saúde na população afetada pelo Bhopal MIC (BMAP). Nossas visões e opiniões apresentadas neste artigo chamam a atenção para prevenir e reduzir as consequências do COVID-19 no BMAP. Da perspectiva da profilaxia com COVID-19, os indivíduos de alto risco do BMAP com condições comórbidas precisam ser identificados por meio de uma visita de porta em porta nas regiões severamente afetadas por gases e aconselhados a manter uma boa higiene respiratória, ingestão regular de dieta que estimule o sistema imunológico e seguir práticas de estilo de vida saudáveis.

Fabrication of hydrophilic medical catheter with hydrogel grafting and the in vivo evaluation of its histo-compatibility / 生物医学工程学杂志

The biocompatible hydrogel was fabricated under suitable conditions with natural dextran and polyethylene glycol (PEG) as the reaction materials. The oligomer (Dex-AI) was firstly synthesized with dextran and allylisocyanate (AI). This Dex-AI was then reacted with poly (ethyleneglycoldiacrylate) (PEGDA) under the mass ratio of 4∶6 to get hydrogel (DP) with the maximum water absorption of 810%. This hydrogel was grafted onto the surface of medical catheter via diphenyl ketone treatment under ultraviolet (UV) initiator. The surface contact angle became lower from (97 ± 6.1)° to (25 ± 4.2)° after the catheter surface was grafted with hydrogel DP, which suggests that the catheter possesses super hydrophilicity with hydrogel grafting. The evaluation after they were implanted into ICR rats subcutaneously verified that this catheter had less serious inflammation and possessed better histocompatibility comparing with the untreated medical catheter. Therefore, it could be concluded that hydrogel grafting is a good technology for patients to reduce inflammation due to catheter implantation, esp. for the case of retention in body for a relative long time.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Work-Related Asthma in Korea - Findings from the Korea Work-Related Asthma Surveillance (KOWAS) program, 2004-2009

PURPOSE: To determine the incidence and epidemiological characteristics of work-related asthma in Korea. METHODS: During 2004-2009, the Korea Work-Related Asthma Surveillance (KOWAS) program collected data on new cases of work-related asthma from occupational physicians, allergy and chest physicians, regional surveillance systems, and workers' compensation schemes. The incidence was calculated on the basis of industry, occupation, sex, age, and region. In addition, the distribution of causal agents was determined. RESULTS: During the study period, 236 cases of work-related asthma were reported, with 77 cases from more than 1 source. A total of 22.0% (n=52) were reported by occupational physicians, 52.5% (n=124) by allergy and chest physicians, 24.2% (n=57) by regional surveillance systems, and 43.2% (n=102) by workers' compensation schemes. The overall average annual incidence was 3.31 cases/million workers, with a rate of 3.78/million among men and 2.58/million among women. The highest incidence was observed in the 50-59-year age group (7.74/million), in the Gyeonggi/Incheon suburb of Seoul (8.50/million), in the furniture and other instrument manufacturing industries (67.62/million), and among craft and related trades workers (17.75/million). The most common causal agents were isocyanates (46.6%), flour/grain (8.5%), metal (5.9%), reactive dyes (5.1%), and solvents (4.2%). CONCLUSIONS: The incidence of work-related asthma in Korea was relatively low, and varied according to industry, occupation, gender, age, and region. Data provided by workers' compensation schemes and physician reports have been useful for determining the incidence and causes of work-related asthma.

Effects of MBL2 polymorphisms in patients with diisocyanate-induced occupational asthma

Diisocyanate (DI) is the most common cause of occupational asthma (OA) in Korea. Mannose-binding lectin (MBL) initiates the lectin complement activation pathway following oxidative stress and plays an important role in the regulation of inflammatory processes. To determine whether there is a genetic association between MBL2 polymorphisms and DI-OA, 99 patients with DI-OA, 99 asymptomatic exposed controls (AECs) and 144 unexposed normal controls were enrolled in this study. Three polymorphisms (-554 G>C, - 431A>C and - 225 G>C) in the MBL2 promoter were genotyped, and serum MBL levels were determined by enzyme-linked immunosorbent assay. Functional variabilities in the promoter polymorphisms were analyzed by a luciferase reporter assay and electrophoretic mobility shift assay (EMSA). A significantly higher frequency of haplotype (ht) 2 [CAG] was noted in the DI-OA group compared with the AEC group (P=0.044). The patients with DI-OA carrying ht2 [CAG] had significantly lower PC20 methacholine levels (P<0.001) than the non-carriers. The serum MBL levels were significantly higher in the DI-exposed subjects (both the DI-OA patients and AECs) carrying ht1 [GAG] (P=0.028). Luciferase activity was significantly enhanced in ht1 [GAG] compared with ht2 [CAG] in human hepatocarcinoma cells (Hep3B) (P=0.002). The EMSA showed that a - 554G probe produced a specific shifted band compared with the - 554C probe. These findings suggest that decreased serum MBL levels due to polymorphisms of the MBL2 gene may increase susceptibility to the development of DI-OA in DI-exposed individuals.

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India.

CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes. AIMS: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg’s equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.

Association of microsatellite instability and chronic obstructive pulmonary disorder in isocyanate-exposed population of Bhopal.

Context: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. Aims: Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC. Settings and Design: The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder. Materials and Methods: Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA) 8 RG and (CA) 8 R[Y-Q] primer. Statistical Analysis Used: Association analyses were performed using regression analysis. Results: The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = −0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence. Conclusions: The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts.

A pragmatic & translational approach of human biomonitoring to methyl isocyanate exposure in Bhopal.

Human biomonitoring has evolved beyond margins to ascertain exposure-response relationship in environmental associated human diseases. As occupational ailments continue to dominate global concerns, biomonitoring strategies have evolved better in terms of evaluating health risks associated with systemic uptake from chronic (long-term) environment exposures. Even though contributions of acute toxic exposures (short-term) towards initiation of disease processes have been gradually recognized, a comprehensive approach delineating mechanistic insights of such an implication remains elusive. Molecular biomonitoring in a strictly selected defined surviving cohort of the infamous Bhopal gas tragedy “as a model”, could provide an unparallel opportunity to discern the long standing implications of acute exposures. Besides comprehending clinical significance of isocyanate toxicity, the results might provide a framework for understanding the molecular repercussions pertaining to a host of other such acute environmental exposures. The investigative strategy might also be helpful in identification of biomarkers with potential for translational research.

Retrospective analysis of lung function abnormalities of Bhopal gas tragedy affected population.

Background & objectives: A large numbers of subjects were exposed to the aerosol of methyl isocyanate (MIC) during Bhopal gas disaster and lung was one of the most commonly affected organs. The aim of the present study was to analyze retrospectively the lung function abnormalities among the surviving MIC exposed population (gas victims) and to compare it with the non-MIC exposed (non gas exposed) population. Methods: The spirometry data of both gas victims and non gas exposed population who attended the Bhopal Memorial Hospital & Research Centre for evaluation of their respiratory complaints from August 2001 to December 2009, were retrospectively evaluated and compared. Results: A total 4782 gas victims and 1190 non gas exposed individuals performed spirometry during the study period. Among the gas victims, obstructive pattern was the commonest (50.8%) spirometric abnormality followed by restrictive pattern (13.3%). The increased relative risk of developing restrictive abnormality among gas victims was observed in 20-29 yr age group only (adjusted relative risk: 2.94, P<0.001). Male gas victims were more affected by severe airflow obstruction than females and the overall increased relative risk (1.33 to 1.45, P<0.001) of developing obstructive pattern among gas victims was observed. Interpretation & conclusions: The present study showed that the relative risk for pulmonary function abnormalities in gas victims was significantly more among those who were young at the time of disaster. Increased smoking habit among gas victims might have played an additive effect on predominance of obstructive pattern in spirometry.

Determination of methyl isocyanate (MIC) in air of workplaces by HPLC / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish the method of detecting the concentrations of methyl isocyanate (MIC) in air of workplaces with high performance liquid chromatographic (HPLC).</p><p><b>METHODS</b>Samples are collected by XAD-7 tubes coated with 1-(2-pyridyl) piperazine (1-2PP). Samples are desorbed with acetonitrile (ACN) and analyzed by high performance liquid chromatography (HPLC) using a fluorescence detector.</p><p><b>RESULTS</b>There was a linear relationship within the range of 0.01 ∼ 10 µg/ml, and the detection limit was 5.3×10(-4) µg/ml. The minimum detectable concentration was 0.01 µg/ml, and the lowest detected concentration was 3.3×10(-3) mg/m(3). The relative standard deviation was 2.2% ∼ 5.3%. The average desorption efficiency was 90% and the sampling efficiencies were 100%. The samples could be stored for 10 days in cold storage condition.</p><p><b>CONCLUSION</b>The present method could meet with the requirements of Guide for establishing occupational health standards-Part4 Determination methods of air chemicals in workplace and be feasible for determination of MIC in workplace air.</p>

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.

PEGylation of polyamidoamine dendrimer and the properties for gene vectors / 药学学报

Polyamidoamine-polyethylene glycol (PAMAM-PEG) copolymers were synthesized using IPDI as coupling reagent by two-step method. The copolymers were characterized by IR spectrum and 1H NMR spectrum, and the PEG conjugating ratios of the copolymers were calculated equal to 10% and 30% separately. MTT assay indicated that after PEGylation a lower cytotoxicity of the copolymers could be found, and with increasing PEG conjugating ratio the cytotoxicity decreased obviously. Agarose gel retardation assay demonstrated that PAMAM-PEG copolymers could be combined with DNA and PAMAM-PEG/DNA complexes were prepared by self-assembly. DLS measurement showed that when N/P > or = 50, the particle size of copolymer/ gene complexes was in a range of 150-200 nm, and the zeta potential was in a range of 10-25 mV. In vitro gene transfection illustrated that when N/P < or = 50, the gene transfection efficiency of PAMAM-PEG copolymers was a little less than that of PAMAM-G5, but the transfection efficiency can be raised by increasing N/P ratio or transfection time. Considering both cytotoxicity and transfection efficiency aspects PAMAM-PEG-13 was more effect than PAMAM-PEG-39 in PEGylation.

Biomarkers Predicting Isocyanate-Induced Asthma

Three diisocyanates can cause occupational asthma (OA): toluene diisocyanate (TDI), 4,4 diphenylmethane diisocyanate (MDI), and 1,6-hexamethylene diisocyanate (HDI). We analyzed potential biomarkers of isocyanate-induced OA, based on investigated immunologic, genetic, neurogenic, and protein markers, because there is no serological testing method. The prevalence of serum IgG to cytokeratin (CK)18 and CK19 in TDI-OA was significantly higher than in controls, although the prevalence of these antibodies was too low for them to be used as biomarkers. Another candidate biomarker was serum IgG to tissue transglutaminase (tTG), because the prevalence of serum specific IgG to tTG was significantly higher in patients with TDI-OA than in controls. The human leukocyte antigen (HLA) DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be used as a genetic marker for TDI-OA in Koreans via enhanced specific IgE sensitization in exposed subjects. The genetic polymorphisms of catenin alpha 3, alpha-T catenin (CTNNA3) were significantly associated with TDI-OA. Additionally, examining the neurokinin 2 receptor (NK2R) 7853G>A and 11424 G>A polymorphisms, the NK2R 7853GG genotype had higher serum vascular endothelial growth factor (VEGF) levels than the GA or AA genotypes among Korean workers exposed to TDI. To identify new serologic markers using a proteomic approach, differentially expressed proteins between subjects with MDI-OA and asymptomatic exposed controls in a Korean population showed that the optimal serum cutoff levels were 69.8 ng/mL for ferritin and 2.5 microg/mL for transferrin. When these two parameters were combined, the sensitivity was 71.4% and the specificity was 85.7%. The serum cytokine matrix metalloproteinase-9 (MMP-9) level is a useful biomarker for identifying cases of TDI-OA among exposed workers. Despite these possible biomarkers, more effort should be focused on developing early diagnostic biomarkers using a comprehensive approach based on the pathogenic mechanisms of isocyanate-induced OA.

Synthesis, characterization and electrospinning of biodegradable polyurethanes based on poly(epsilon-caprolactone) and L-lysine diisocynate / 生物医学工程学杂志

A novel diisocyanate, i. e. lysine ethyl ester diisocyanate (LDI), was prepared by the present authors. Poly (epsilon-caprolactone) (PCL) (M(n) = 2000) was used for reacting with LDI to form prepolymer, and then the chain was extended with butanediol (BDO) to form polyurethane (PU). PU was characterized by gel permeation chromatography, FTIR and 1H-NMR. Mechanical properties test revealed that PU possesses excellent tensile strength. Hydrolytic degradation and enzymatic degradation of PU films showed that PU is biodegradable. Finally, vascular scaffold of PU was fabricated by electrospinning. Morphological and biomechanical properties of scaffold were examined. The tensile strength was 8MPa, suture retention strength 12N, porosity 75% and burst pressure strength 150-170 kPa. Cytotoxicity and cell adhesion showed that PU scaffolds are biocompatible. These results demonstrate that PU vascular scaffolds possess excellent physical strength and biocompatibility and can be developed as substitutes for native blood vessels.

Synthesis, characterization and blood compatibility studies of waterproof breathable polyurethanes / 生物医学工程学杂志

Adopting the two-step method and changing the proportion between PEG (Polyethylene glycol) and PTMG (poly (tetrahydrofuran), we used the MDI (4,4'-diphenylmethane diisocyanate) and short chain extender BDO (1,4-butanediol) as hard segment, the PTMG and PEG as soft segment, and hence prepared a series of polyether-based thermoplastic polyurethanes. FTIR showed the structure character of these polyurethanes. The determination of mechanics property and water contact angles revealed their good mechanics properties and hydrophilicity. Blood compatibility was evaluated by hemolysis test and platelet adhesion test, which revealed their good hemocompatibility. So those polyurethanes may be of wide application in the future.

Antioxidant and antimicrobial activities of Egyptian eruca sativa seed volatile oil

The percent yield of Egyptian Eruce sativa seeds volatile oil obtained by water distillation was 0.45%. The volatile oil components were separated and identified by gas chromatography / mass spectrometry. Twelve constituents were identified and found to be belonging to isothiocyanates group and nitriles group. The major constituent was 4- methyl thiobutyl isothiocyanates which represented 94.10%. Volatile oil was tested to evaluate its antioxidant activity.200 ppm and 400 ppm of Eruca sativa seeds volatile oil were added to sunflower oil. Stability of sunflower oil was determined by rancimat method, before and after addition of the volatile oil. Sunflower oil was also mixed with 200 ppm synthetic antioxidant agent [BHT]. oxidative stability was 6.8 hr, 16.8 hr, 7.4 hr and 14.9 hr for sunflower oil [control], Sunflower oil mixed with 200 ppm BHT, Sunflower oil mixed with 200 ppm volatile oil and sunflower oil mixed with 400 ppm volatile oil, respectively. The volatile oil was tested to evaluate its antimicrobial activity against some bacterial strains; namely Micrococcus spp.,Pseudomonas spp., Bacillus cereus and Enterobacter aerogenes. fungal Strains; namely Aspergillus niger and Aspergillus flavus, as well as against the yeast, Sacchromyces cereviseae. The diameter of the zone inhibition was taken as a criterion of antimicrobial activity at different concentrations of the volatile oil, which had a significant effect against Micrococcus spp., Pseudomonas spp. and S. cereviseae

Diagnosis and Prevention of Diseases Induced by Isocyanate

Isocyanates are among the most frequent causes of occupational asthma in industrialized countries. Early diagnosis of diisocyanate asthma followed by prompt termination of chemical exposure can prevent chronic morbidity due to persistent asthma. Chronic exposure to isocyanates also induces hypersensitivity pneumonitis (HP). The accurate diagnosis of diisocynate asthma requires a systematic approach that combines information obtained from the occupational history, immunologic tests and physiologic studies. The prevention of health problems from toluene diisocyanate (TDI), 4,4’-methylenediphenyl diisocyanate (MDI) and 1,6’-hexamethylene diisocyanate (HDI) is essential for all those handling the chemicals. Regulatory exposure limits should be observed. However, wheezing, coughing or even asthmatic attacks may occur after exposure much below the regulatory exposure limits especially in sensitive individuals. Preventing or minimizing exposure is of prime importance and should be supported by the installation of engineering controls, by education of the workforce, by regular monitoring of the workplace exposure and by medical surveillance. To prevent such asthma it is suggested that workers should be tested airway sensitivity and should avoid working in areas that have dust containing specific-IgE. Such tests must be periodically performed after working. Symptoms induced by isocyanate need earlier discover and early isolation of the associated individuals.

Review of the Occupational Exposure to Isocyanates:Mechanisms of Action

Polyurethanes are useful polymers in a large variety of technical and consumer products that are generally made from diisocyanates and polyols or similar compounds. Toluene diisocyanate (TDI), 4,4’-methylenediphenyl diisocyanate (MDI) and 1,6’-hexamethylene diisocyanate (HDI) are useful for polyurethane products. Isocyanates are reactive chemicals that can be handled without problems in manufacturing or technical environments. In general, consumers may only have contact with these chemicals on rare occasions. The objective of this study was to review the mechanisms of action of inhalation of isocyanates. This paper describes, in summary, the potential occupational exposure to isocyanates, the chemistry and reactivity of isocyanates, the results from genotoxicity studies, investigative toxicity studies, metabolism and results from epidemiology studies on isocyanate-exposed workers. The overall conclusion is that because humans are not exposed to high levels of respiratory isocyanate particles, concerns over the possible development of lung tumors should not be relevant. There are many mechanisms of action induced by isocyanates, but those entities are unclear. This is because these mechanisms act simultaneously and are complex.

Airway hyperresponsiveness among workers exposed to isocyanates at Yeocheon petrochemical plant / 천식및알레르기

OBJECTIVE: To investigate the prevalence of airway hyperresponsiveness induced by isocyanate at one petrochemical industry complex in Yeochon, Korea. METHOD: Questionnaires, allergic skin prick test, toluene diisocyanate (TDI)-specific IgE, and non-specific airway hyperresponsiveness (AHR) were studied in 73 exposed workers and 27 control subjects. Methacholine challenge tests were done and bronc hial responsiveness (BR index) was defined as log (% fall of FEV1)/ log (last concentration of methacholine +10). RESULTS: Twenty-three workers (31.5% ) had respiratory symptoms, 21 had nasal symptoms, and eight had skin symptoms. Exposed workers with respiratory symptoms (n=22) had significantly higher BR index than those without them (0.82+/-0.06 vs 0.60+/-0.02, p0.05). Specific IgE antibodies were found in 19.7% of exposed workers. FEV, showed a significant negative correlation with BR index (r =-0.25, p<0.05). Poor correlation was noted between BR index and atopy, smoking status, or exposure duration. CONCLUSION: These findings suggest that workers exposed to isocyanates are at higher risk of airway hyperresponsiveness.

Prognostic factors in patients with reactive dye or isocyanate-induced occupational asthma after avoidance of causative agents / 천식및알레르기

BACKGROUND: Although occupational asthma is defined as a reversible airway obstruction causally related to exposure in the working environment, many occupational asthmatics complain of asthmatic symptoms despite avoidance of the causative agent. Subjects and methods. Twenty-nine patients with occupational asthma who had been confirmed by specific bronchial challenge with reactive dye or isocyanates and had avoided the causative agent for at least 6 months were included in this study. A questionnaire about asthmatic symptoms and medication requirements, a lung functiontest, and a methacholine bronchial provocation test were performed. RESULTS: Asthmatic symptoms at follow-up were remitted in seven (41.2%) isocyanate-induced asthmatics, but none with reactive dye-induced asthma were remitted. At follow-up, the symptom-medication score and FEV1 were significantly improved in isocyanate-induced asthmatics than in those with reactive dye-induced asthma, but the geometric mean of PC20-methacholine was not different between the two groups. Among 17 isocyanate-induced asthmatics, a duration from symptom onset to avoidance was significantly shorter in the remission group than in the nonremission group, although the symptom-medication scores, FEV1 (% predictive value) and logPC20-methacholine at an initial diagnosis, and follow-up period defined as duration from avoidance to follow-up, showed no difference between the two groups. CONCLUSION: The outcome of occupational asthma may be determined by the causative agents and the duration from onset of asthmatic symptoms to avoidance.