We conducted a repeated exposure-assessment survey for task-based breathing-zone concentrations (BZCs) of monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI) during spray painting on 47 automotive spray painters from North Carolina and Washington State. We report here the use of linear mixed modeling to identify the primary determinants of the measured BZCs. Both one-stage (N = 98 paint tasks) and two-stage (N = 198 paint tasks) filter sampling was used to measure concentrations of HDI, uretidone, biuret, and isocyanurate. The geometric mean (GM) level of isocyanurate (1410 μg m−3) was higher than all other analytes (i.e. GM < 7.85 μg m−3). The mixed models were unique to each analyte and included factors such as analyte-specific paint concentration, airflow in the paint booth, and sampler type. The effect of sampler type was corroborated by side-by-side one- and two-stage personal air sampling (N = 16 paint tasks). According to paired t-tests, significantly higher concentrations of HDI (P = 0.0363) and isocyanurate (P = 0.0035) were measured using one-stage samplers. Marginal R2 statistics were calculated for each model; significant fixed effects were able to describe 25, 52, 54, and 20% of the variability in BZCs of HDI, uretidone, biuret, and isocyanurate, respectively. Mixed models developed in this study characterize the processes governing individual polyisocyanate BZCs. In addition, the mixed models identify ways to reduce polyisocyanate BZCs and, hence, protect painters from potential adverse health effects.
air sampling; exposure determinants; hexamethylene diisocyanate; isocyanate; statistical modeling
To study inhalation and dermal exposure to hexamethylene diisocyanate (HDI) and its oligomers as well as personal protection equipment (PPE) use during task performance in conjunction with urinary hexamethylene diamine (HDA) in car body repair shop workers and industrial spray painters.
Personal task based inhalation samples (n = 95) were collected from six car body repair shops and five industrial painting companies using impingers with di‐n‐butylamine (DBA) in toluene. In parallel, dermal exposure was assessed using nitril rubber gloves. Gloves were submerged into DBA in toluene after sampling. Analysis for HDI and its oligomers was performed by LC‐MS/MS. Urine samples were collected from 55 workers (n = 291) and analysed for HDA by GC‐MS.
Inhalation exposure was strongly associated with tasks during which aerosolisation occurs. Dermal exposure occurred during tasks that involve direct handling of paint. In car body repair shops associations were found between detectable dermal exposure and glove use (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.09 to 0.57) and inhalation exposure level (OR 1.34, 95% CI 0.97 to 1.84 for a 10‐fold increase). HDA in urine could be demonstrated in 36% and 10% of car body repair shop workers and industrial painting company workers respectively. In car body repair shops, the frequency of detectable HDA was significantly elevated at the end of the working day (OR 2.13, 95% CI 1.07 to 4.22 for 3–6 pm v 0–8 am). In both branches HDA was detected in urine of ∼25% of the spray painters. In addition HDA was detected in urine of a large proportion of non‐spray painters in car body repair shops.
Although (spray) painting with lacquers containing isocyanate hardeners results in the highest external exposures to HDI and oligomers, workers that do not perform paint related tasks may also receive a considerable internal dose.
isocyanate; oligomers; dermal; biomonitoring; spray painting
Urinary 1,6-hexamethylene diamine (HDA) may serve as a biomarker for systemic exposure to 1,6-hexamethylene diisocyanate (HDI) in occupationally exposed populations. However, the quantitative relationships between dermal and inhalation exposure to HDI and urine HDA levels have not been established. We measured acid-hydrolyzed urine HDA levels along with dermal and breathing-zone levels of HDI in 48 automotive spray painters. These measurements were conducted over the course of an entire workday for up to three separate workdays that were spaced approximately 1 month apart. One urine sample was collected before the start of work with HDI-containing paints and subsequent samples were collected during the workday. HDA levels varied throughout the day and ranged from nondetectable to 65.9 μg l−1 with a geometric mean and geometric standard deviation of 0.10 μg l−1 ± 6.68. Dermal exposure and inhalation exposure levels, adjusted for the type of respirator worn, were both significant predictors of urine HDA levels in the linear mixed models. Creatinine was a significant covariate when used as an independent variable along with dermal and respirator-adjusted inhalation exposure. Consequently, exposure assessment models must account for the water content of a urine sample. These findings indicate that HDA exhibits a biphasic elimination pattern, with a half-life of 2.9 h for the fast elimination phase. Our results also indicate that urine HDA level is significantly associated with systemic HDI exposure through both the skin and the lungs. We conclude that urinary HDA may be used as a biomarker of exposure to HDI, but biological monitoring should be tailored to reliably capture the intermittent exposure pattern typical in this industry.
biomarkers; creatinine; dermal exposure; 1,6-hexamethylene diamine; 1,6-hexamethylene diisocyanate; inhalation exposure; urine analysis
Quantification of amines in biological samples is important for evaluating occupational exposure to diisocyanates. In this study, we describe the quantification of 1,6-hexamethylene diamine (HDA) levels in hydrolyzed plasma of 46 spray painters applying 1,6-hexamethylene diisocyanate (HDI)-containing paint in vehicle repair shops collected during repeated visits to their workplace and their relationship with dermal and inhalation exposure to HDI monomer. HDA was detected in 76% of plasma samples, as heptafluorobutyryl derivatives, and the range of HDA concentrations was ≤0.02–0.92 μg l−1. After log-transformation of the data, the correlation between plasma HDA levels and HDI inhalation exposure measured on the same workday was low (N = 108, r = 0.22, P = 0.026) compared with the correlation between plasma HDA levels and inhalation exposure occurring ∼20 to 60 days before blood collection (N = 29, r = 0.57, P = 0.0014). The correlation between plasma HDA levels and HDI dermal exposure measured on the same workday, although statistically significant, was low (N = 108, r = 0.22, P = 0.040) while the correlation between HDA and dermal exposure occurring ∼20 to 60 days before blood collection was slightly improved (N = 29, r = 0.36, P = 0.053). We evaluated various workplace factors and controls (i.e. location, personal protective equipment use and paint booth type) as modifiers of plasma HDA levels. Workers using a downdraft-ventilated booth had significantly lower plasma HDA levels relative to semi-downdraft and crossdraft booth types (P = 0.0108); this trend was comparable to HDI inhalation and dermal exposure levels stratified by booth type. These findings indicate that HDA concentration in hydrolyzed plasma may be used as a biomarker of cumulative inhalation and dermal exposure to HDI and for investigating the effectiveness of exposure controls in the workplace.
biomarker; dermal exposure; 1,6-hexamethylene diamine (HDA); 1,6-hexamethylene diisocyanate (HDI); inhalation exposure; plasma
Rationale: Associations between oligomeric isocyanate exposure, sensitization, and respiratory disease have received little attention, despite the extensive use of isocyanate oligomers.
Objectives: To investigate exposure–response relationships of respiratory symptoms and sensitization in a large population occupationally exposed to isocyanate oligomers during spray painting.
Methods: The prevalence of respiratory symptoms and sensitization was assessed in 581 workers in the spray-painting industry. Personal exposure was estimated by combining personal task-based inhalatory exposure measurements and time activity information. Specific IgE and IgG to hexamethylene diisocyanate (HDI) were assessed in serum by ImmunoCAP assay and enzyme immunoassays using vapor and liquid phase HDI–human serum albumin (HDI–HSA) and HSA conjugates prepared with oligomeric HDI.
Measurements and Main Results: Respiratory symptoms were more prevalent in exposed workers than among comparison office workers. Log–linear exposure–response associations were found for asthmalike symptoms, chronic obstructive pulmonary disease–like symptoms, and work-related chest tightness (prevalence ratios for an interquartile range increase in exposure of 1.2, 1.3 and 2.0, respectively; P ⩽ 0.05). The prevalence of specific IgE sensitization was low (up to 4.2% in spray painters). Nevertheless, IgE to N100 (oligomeric HDI)–HSA was associated with exposure and work-related chest tightness. The prevalence of specific IgG was higher (2–50.4%) and strongly associated with exposure.
Conclusions: The results provide evidence of exposure–response relationships for both work-related and non–work-related respiratory symptoms and specific sensitization in a population exposed to oligomers of HDI. Specific IgE was found in only a minority of symptomatic individuals. Specific IgG seems to be merely an indicator of exposure.
oligomer; isocyanate; asthma; spray painter; sensitization
Isocyanate chemicals essential for polyurethane production are widely used industrially, and are increasingly found in consumer products. Asthma and other adverse health effects of isocyanates are well-documented and exposure surveillance is crucial to disease prevention. Hexamethylene diisocyanate (HDI)-specific serum immunoglobulin G (IgG) was evaluated as an exposure biomarker among workers at a US Air Force Air Logistics Center, which includes a large aircraft maintenance facility.
HDI-specific IgG (HDI-IgG) titers in serum samples (n = 74) were measured using an enzyme-linked immunosorbent assay based upon the biuret form of HDI conjugated to human albumin. Information on personal protective equipment (PPE), work location/tasks, smoking, asthma history, basic demographics, and HDI skin exposure was obtained through questionnaire.
HDI-specific serum IgG levels were elevated in n = 17 (23%) of the workers studied. The prevalence and/or end-titer of the HDI-IgG was significantly (P < 0.05) associated with specific job titles, self-reported skin exposure, night-shift work, and respirator use, but not atopy, asthma, or other demographic information. The highest titers were localized to specific worksites (C-130 painting), while other worksites (generator painting) had no or few workers with detectable HDI-IgG.
HDI-specific immune responses (IgG) provide a practical biomarker to aid in exposure surveillance and ongoing industrial hygiene efforts. The strategy may supplement current air sampling approaches, which do not assess exposures via skin, or variability in PPE use or effectiveness. The approach may also be applicable to evaluating isocyanate exposures in other settings, and may extend to other chemical allergens.
biomarker; exposure; HDI; hygiene; occupational
Hexamethylene diisocyanate (HDI) is used widely to manufacture polyurethanes for paints and coatings. It is an irritant and a chemical asthmagen. The U.S. Occupational Safety and Health Administration time-weighted average permissible exposure limit is 5 ppb and the ceiling limit is 20 ppb. We sought to develop a sensitive and specific immuno-bioassay to supplement workplace air monitoring and detect recent HDI exposure. For this, we produced rabbit antiserum to HDI-adducted keyhole limpet hemocyanin (HDI-KLH). The specificity of the antiserum was demonstrated by its reaction with a variety of HDI-conjugated proteins and the absence of reactions with conjugates of other diisocyanates, namely toluene diisocyanate and diphenyl methylene diisocyanate. Four immunoassays were developed and compared for their ability to detect decreasing quantities of HDI-adducted human serum albumin (HSA) containing 2 mol HDI adduct per mol HSA (HDI(2)-HSA) as determined by matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry. The sensitivities of some of the assays are within the range (0.82-45 nM) of current analytic methods. A Western analysis procedure has a sensitivity of 600 nM HDI adduct on HSA. ELISA inhibition assay, in which microtiter plates are coated with the HDI(2)-HSA antigen, has a sensitivity of 300 nM HDI adduct. An immunoblot assay has a sensitivity of 9 nM HDI adduct. The most sensitive bioassay (1.8 nM HDI adduct) is a three-antibody sandwich ELISA in which wells of microtiter plates are coated with the IgG fraction of the anti-HDI-KLH antisera. Compared with analytic methods for HDI biomonitoring, the immunoassays are faster and less costly and accommodate numerous samples simultaneously. The assays have the potential to affect industrial biomonitoring programs significantly.
OBJECTIVES--To examine if car painters who work with polyurethane paints that contain hexamethylenediisocyanate (HDI) and hexamethylenediisocyanate biuret trimer (HDI-BT) develop acute as well as chronic impairment of lung function. METHODS--In this study data were reanalysed from two earlier studies on a group of car painters to see if a decrease in lung function within the week is a marker of vulnerability in those workers. Data on changes in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) within the week were available for 20 car painters who were also examined six years later. RESULTS--10 men showed a decline in FVC within the week. There were no significant differences in age, duration of employment, exposures during the follow up period, or smoking between car painters who had decline in lung function within the week and car painters who had not. A significant correlation was found between the change in FVC within the week and the long term (six year) change in FVC, standardised for the effects of aging and smoking, and adjusted for the number of peak exposures. CONCLUSIONS--The results suggest that the decrease in FVC within the week might serve as a guide to identify car painters at risk of a further decrement in lung function above the effects of aging, smoking, and exposure.
OBJECTIVES: To develop a method for the measurement of a metabolite of hexamethylene diisocyanate (HDI), an isocyanate, and use it to assess the exposure of sprayers employed in motor vehicle repair shops. METHODS: Urine samples were taken from sprayers wearing personal protective equipment and spraying in booths or with local exhaust ventilation, from bystanders, and from unexposed subjects. Samples were analyzed for a metabolite of HDI, hexamethylene diamine (HDA), by gas chromatography-mass spectrometry (GC-MS). RESULTS: HDA was detected in four sprayers and one bystander out of 22 workers. No HDA was detected in the urine of unexposed subjects. CONCLUSIONS: Exposure to isocyanates still occurs despite the use of personal protective equipment and the use of a booth or extracted space. Health surveillance is likely to be required to provide feedback on the adequacy of controls even if such precautions are used and to identify cases of early asthma. Biological monitoring can provide a useful additional tool to assess exposure and the adequacy of controls in this group of exposed workers.
OBJECTIVE--This study was undertaken to assess whether contaminated personal clothing worn beneath a coverall (normal workwear) is a source of potentially significant dermal exposure to polycyclic aromatic hydrocarbons (PAHs) in coal liquefaction workers. METHODS--An intervention study was conducted over a two week period involving 10 workers that reflected the range of activities performed at the factory. A cross over design was used to examine the influence of normal workwear (personal clothing worn beneath a coverall) and intervention workwear (new coverall, shirt, trousers, underwear, socks, and boots) upon excretion of urinary 1-hydroxypyrene (1-OHP) and skin pad deposition of pyrene. RESULTS--The impact of intervention was noted in three ways: (1) A notable reduction (55%) in the mass of 1-OHP excreted on the first day of the intervention phase was found. The median reduction in mass excreted (22.7 nmol) was significant from zero at the 5% level; (95% confidence interval (95% CI) 9.5-40.8 nmol). (2) A notable reduction (82%) in skin pad deposition of pyrene on the first day of the intervention phase was found. The median reduction of 13.20 ng.cm-2 was significant from zero at the 5% level; (95% CI 7.3-26.4 ng.cm-2). (3) About a 50% reduction in 1-OHP concentration over the working week occurred during the intervention phase; an increase of 2.07 mumol/mol creatinine was found from the start to the end of the work period during the intervention phase compared with an increase of 4.06 mumol/mol creatinine during the normal phase. This reduction was not significant at the 5% level. CONCLUSION--The results indicate that on the first day of the working week investigated, significant reductions in absorbtion (as measured by excretion of urinary 1-OHP) and deposition of PAHs (as measured by skin pad deposition of pyrene) can be effected by improvements in workwear policy. The impact of the improved workwear regimen was also detected by reduction in spot urinary 1-OHP concentrations, although this effect was less pronounced. One implication of the findings is that exposure to PAHs may arise from workers' own contaminated personal clothing. As a consequence of this study an improved workwear policy has been implemented at the factory.
1,6-hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenges in HDI biomarker analysis including the quantification of N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N′-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA) in urine samples based on previously established methods for HDA analysis. In addition, we describe the optimization of reaction conditions for the synthesis of monoacetyl-HDA and diacetyl-HDA, and utilize these standards for the quantification of these metabolites in the urine of three occupationally exposed workers. Diacetyl-HDA was present in untreated urine at 0.015 – 0.060 μg/l. Using base hydrolysis, the concentration range of monoacetyl-HDA in urine was 0.19 – 2.2 μg/l, 60-fold higher than in the untreated samples on average. HDA was detected only in one sample after base hydrolysis (0.026 μg/l). In contrast, acid hydrolysis yielded HDA concentrations ranging from 0.36 to 10.1 μg/l in these three samples. These findings demonstrate HDI metabolism via N-acetylation metabolic pathway and protein adduct formation resulting from occupational exposure to HDI.
1,6-hexamethylene diamine (HDA); biomarker; 1,6-hexamethylene diisocyanate (HDI); diisocyanate-induced asthma
The association between spray paint exposure and bone remodeling received little attention despite the high usage of spray paints in automobile industries, steel furniture workshops etc.
The present study was aimed at investigating the level of serum markers of bone formation in spray painters. The spray painting subjects were selected from automobile body repair workshops in Chennai region of TamilNadu which constitutes 30% of India's automobile industry.
Setting and Design:
All the study subjects, exposed to spray paint were working in a workshop without standard spraying room and did not wore any aerosol removing respirator. The controls were selected from random population irrespective of occupation. Data relevant to the socioeconomic features and personal history was collected using a questionnaire. The current study included 50 spray painters and 25 control subjects of same age group.
Materials and Methods:
We examined the level of serum calcium, serum phosphorus, serum differentiation markers of bone such as alkaline phosphatase (bone specific) and serum osteocalcin in which these levels were found to be high in serum of spray painters.
The current study concludes dysregulation in bone remodeling of spray painters exposed to chronic solvents and paint pigments.
Bone remodeling; paint pigments; serum markers
Water based paints contain organic solvents and many additives, such as biocides, surfactants, pigments, binders, amines, and monomers. The chemical complexity may introduce new potential health hazards to house painters, in particular irritative and allergic disorders. This study was performed to compare how house painters experience work with water based paints or solvent based paints, and to evaluate whether exposure to water based paints increases mucous membrane and dermal symptoms among house painters. 255 male house painters aged 20 to 65 were invited to participate in the study. Controls were two industrial populations, in total 302 men, without exposure to water based paints. Self administered questionnaires were used to assess the painter's experiences of working with different types of paints and the occurrence of symptoms in the exposed and unexposed groups. Hygiene measurements were performed during normal working days when only water based paints and no solvent based paints were used. The painters were exposed to low concentrations of dust, metals, ammonia, formaldehyde, and volatile organic compounds. The work environment was considered better when working with water based paints than with solvent based paints. There were more complaints of frequent urination when working with water based paint. Taste or olfactory disturbances were less common. General as well as work related eye and skin irritation was more common among the exposed workers. For other symptoms no significant differences were found. The study indicates that the introduction of water based paints has improved the work environment for house painters. Water based paints cause less discomfort and airway irritation than the earlier solvent based paints. Adverse general health effects seem low. Some of the painters may have dermal symptoms caused by the components in water based paints.
Clothes-borne transmission is an important way of spread of infection from patient to patient which is not interrupted by common cotton gowns. New barrier garments were designed from spun-bonded olefin that, in particle penetration tests, was 100 times better as a filter than cotton cloth. Three designs, a gown, a loose coverall and a close overall, were compared with each other and with conventional cotton gowns in experimental exercise and nursing procedures. Staphylococcus aureus from burned patients were used as markers. The close coverall was 4-7 times better than the loose coverall or gown in preventing the soiling of clothes worn underneath it, but appeared to permit substantially more transfer from garments underneath it to a mock 'patient' and to the air than did the looser garments. A cotton gown reduced the soiling of clothes underneath it by more than 10 times and the contamination of a mock patient by more than 30 times as compared with no barrier garment. The close coverall further diminished the contamination of clothes but not the transfer to the patient. The possible mechanisms for the discrepancy between particle transmission tests annd experimental porcedures are discussed.
In this study we developed an in vitro exposure model to investigate the effects of hexamethylene diisocyanate (HDI) on human airway epithelial cells at the cellular and molecular level. We used immunofluorescence analysis (IFA) to visualize the binding and uptake of HDI by airway epithelial cell lines (A549 and NCI-NCI-H292) and microarray technology to identify HDI sensitive genes. By IFA, we observed that subcytotoxic concentrations of HDI form microscopic micelles that appear to be taken up by cells over a 3-hr period postexposure. Microarray analysis (4.6K genes) of parallel cultures identified four genes (thioredoxin reductase, dihydrodiol dehydrogenase, TG interacting factor, and stanniocalcin) whose mRNA levels were up-regulated after HDI exposure. Northern analysis was used to confirm that HDI increased message levels of these four genes and to further explore the dose dependence and kinetics of the response. The finding that HDI exposure increases thioredoxin reductase expression supports previous studies suggesting that HDI alters thiol-redox homeostasis, an important sensor of cellular stress. Another of the HDI-increased genes, a dihydrodiol dehydrogenase, encodes a protein previously shown to be specifically susceptible to HDI conjugation, and known to detoxify other hydrocarbons. Together, the data describe a novel approach for investigating the effects of HDI binding and uptake by human airway epithelial cells and begin to identify genes that may be involved in the acute response to exposure.
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.
isocyanates; diisocyanate; review; diagnosis; prevention
To determine the effectiveness of protective suits and gloves by biomonitoring.
Fifteen male spray painters at a ship coating factory were studied for two weeks. Workers wore no protective clothing during the first week and wore protective suits and gloves during the second week. Sampling was conducted on four consecutive working days each week. Ethyl benzene and xylene in the air were collected by using 3M 3500 organic vapour monitors. Urine was collected before and after each work shift.
Urinary mandelic acid (MA) and methyl hippuric acid (MHA) levels were divided by the personal exposure concentrations of ethyl benzene and xylene, respectively. Mean (SE) corrected MA and MHA concentrations in the first week were 1.07 (0.18) and 2.66 (0.68) (mg/g creatinine)/(mg/m3), and concentrations in the second week were 0.50 (0.12) and 1.76 (0.35) (mg/g creatinine)/(mg/m3) in the second week, respectively. Both MA and MHA concentrations in the second week (when spray painters wore protective suits and gloves) were lower than in the first week, respectively (p<0.001, p = 0.011). Mean decrease in MA and MHA biomarkers were 69% and 49%, respectively.
This study successfully evaluated the effectiveness of chemical protective suits and gloves by using biomarkers as urinary MA and MHA. This method is feasible for determining the performance of workers wearing personal protective equipment. Moreover, the experimental results suggest that dermal exposure may be the major contributor to total body burden of solvents in spray painters without protective suits and gloves.
Isocyanates, a leading cause of occupational asthma, are known to induce adaptive immune responses; however, innate immune responses, which generally precede and regulate adaptive immunity, remain largely uncharacterized.
Identify and characterize cellular, molecular and systemic innate immune responses induced by hexamethylene diisocyanate (HDI).
Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with HDI-albumin conjugates or control antigen, and changes in phenotype, gene, and protein expression were characterized by flow cytometry, microarray, Western blot and ELISA. Cell uptake of isocyanate was visualized microscopically using HDI-albumin conjugates prepared with fluorescently-labeled albumin. In vivo, human HDI exposure was performed via specific inhalation challenge, and subsequent changes in PBMCs and serum proteins were measured by flow cytometry and ELISA. Genotypes were determined by PCR.
Human monocytes take-up HDI-albumin conjugates and undergo marked changes in morphology and gene/protein expression in vitro. The most significant (p 0.007 – 0.05) changes in mircoarray gene expression were noted in lysosomal genes, especially peptidases and proton pumps involved in antigen processing. Chemokines that regulate monocyte/macrophage trafficking (MIF, MCP-1), and pattern recognition receptors that bind chitin (chitinases) and oxidized low-density lipoprotein (CD68) were also increased following isocyanate-albumin exposure. In vivo, HDI exposed subjects exhibited an acute increase in the percentage of PBMCs with the same HDI-albumin responsive phenotype characterized in vitro (HLA-DR+/CD11c+ with altered light scatter properties). An exposure-dependent decrease (46±11%; p<0.015) in serum concentrations of chitinase-3-like-1 was also observed, in individuals that lack the major (type 1) human chitinase (due to genetic polymorphism), but not in individuals possessing at least one functional chitinase-1 allele.
Previously unrecognized innate immune responses to HDI and HDI-albumin conjugates could influence the clinical spectrum of exposure reactions.
Isocyanate; Innate; Monocyte; Macrophage; Chitinase; CD68; Albumin; MIF; Cathepsin; Exposure; Asthma
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.
diisocyanate; immunology; genotoxicity; carcinogenicity; review
Finding an ideal biomaterial with the proper mechanical properties and biocompatibility has been of intense focus in the field of soft tissue engineering. This paper reports on the synthesis and characterization of a novel crosslinked urethane-doped polyester elastomer (CUPOMC), which was synthesized by reacting a previously developed photocrosslinkable poly (octamethylene maleate citrate) (POMC) prepolymers (pre-POMC) with 1,6-hexamethylene diisocyanate (HDI) followed by thermo- or photo-crosslinking polymerization. The mechanical properties of the CUPOMCs can be tuned by controlling the molar ratios of pre-POMC monomers, and the ratio between the prepolymer and HDI. CUPOMCs can be crosslinked into a 3D network through polycondensation or free radical polymerization reactions. The tensile strength and elongation at break of CUPOMC synthesized under the known conditions range from 0.73±0.12MPa to 10.91±0.64MPa and from 72.91±9.09% to 300.41±21.99% respectively. Preliminary biocompatibility tests demonstrated that CUPOMCs support cell adhesion and proliferation. Unlike the pre-polymers of other crosslinked elastomers, CUPOMC pre-polymers possess great processability demonstrated by scaffold fabrication via a thermally induced phase separation method. The dual crosslinking methods for CUPOMC pre-polymers should enhance the versatile processability of the CUPOMC used in various conditions. Development of CUPOMC should expand the choices of available biodegradable elastomers for various biomedical applications such as soft tissue engineering.
Biodegradable Elastomer; Polyester; Soft Tissue Engineering; Thermo-Crosslinking; UV-Crosslinking
A 23-year-old spray painter developed contact dermatitis and respiratory difficulty characterized by small airways obstruction shortly after the polyfunctional aziridine cross-linker CX-100 began to be used in his workplace as a paint activator. The symptoms resolved after he was removed from the workplace and was treated with inhaled and topical steroids. Painters may have an increased risk of asthma due to exposure to a variety of agents, such as isocyanates, alkyd resins, and chromates. This case illustrates the importance of using appropriate work practices and personal protective equipment to minimize exposure. Occupational asthma is diagnosed by a history of work-related symptoms and exposure to known causative agents. The diagnosis is confirmed by serial pulmonary function testing or inhalational challenge testing. The risk of asthma attributable to occupational exposures is probably underappreciated due to underreporting and to inappropriate use of narrow definitions of exposure in epidemiologic studies of attributable risk.
Epoxy resin systems have been associated with occupational asthma in several case reports, but medical publications contain little on the potential adverse respiratory effects of these chemicals in exposed worker populations. To further evaluate the association of workplace exposure to epoxy paints and respiratory dysfunction, the cross workshift changes in pulmonary function and symptoms of 32 shipyard painters exposed to epoxy paints were compared with 28 shipyard painters not exposed to epoxy paints. The prevalence of lower respiratory tract symptoms was significantly higher among painters exposed to epoxy paints compared with controls. Among exposed painters the mean cross workshift change in forced expiratory volume in one second (FEV1) (-3.4%) was greater than the decrement in the non-exposed group (-1.4%). A significant linear relation was seen between % decrement in FEV1 and hours of exposure to epoxy paints. This study suggests that epoxy resin coatings as used by shipyard painters are associated with increased lower respiratory tract symptoms and acute decrements in FEV1. Adequate respiratory protection and medical surveillance programmes should be established in workplaces where exposure to epoxy resin systems occurs.
Diisocyanates are widely used in surface coatings, polyurethane (PUR) foams, adhesives, resins, elastomers, binders, and sealants. Isocyanate exposure is irritative to the skin, mucous membranes, eyes, and respiratory tract. The most common adverse health outcome associated with isocyanate exposure is asthma due to sensitization.
The goal of this study is to find statistical predictive model to determine the relationship between airborne hexamethylene diisocyanate (HDI) and selective psychrometric variables.
Materials and Methods:
All air samplers (by midget impinger) were collected by mini personal sampler pump fixed to work stations near the source of pollution. The air samples and psychrometric parameters were separately collected and determined in a working shift for three periods of 2 h, each at a flow rate of 2 l/min in an impinger containing a solution of reagent of dimethyl sulfoxide in tryptamine [US National Instituteof Occupational Safety and Health (NIOSH), 1994].
There was a significant correlation between HDI concentration and relative humidity and dry bulb temperature (P < 0.05). No significant correlation was seen between altitude and dimension of PUR factories (P > 0.05).
The finding of the study may be a useful initial tool in estimating possible HDI pollution situation in the PUR workplaces, based on simple psychrometric factors (indoor air temperature and relative humidity).
Diisocyanate; dry bulb temperature; hexamethylene diisocyanate concentration; regression; relative humidity
OBJECTIVES—To determine whether the risk of irritant symptoms in painters is related to their exposure to paint.
METHODS—The prevalences of skin, eye and nasal symptoms were compared in 260 United Kingdom and 109 Chinese dockyard painters, 539 British community controls, and 255 Chinese dockyard controls, relative to their exposure to paints.
RESULTS—Painters showed an excess of irritant symptoms compared with controls. Adjusted relative risks (RRs) (95% confidence interval (95% CI) were: for skin irritation 1.58 (1.19 to 2.08) in British painters and 2.68 (1.73 to 4.09) in Chinese painters; for eye irritation, 1.41 (0.98 to 2.05) and 3.01 (1.90 to 4.76); and for nasal irritation, 1.53 (1.10 to 2.14) and 6.73 (3.53 to 12.82), respectively. Exposure duration-response relations were found for these symptoms; the risks decreased with time after exposure ended.
CONCLUSIONS—Irritant symptoms occur more often in dockyard painters than in controls, and this is likely to be a response to exposure to paint.
Keywords: paint exposures; dockyard painting; health effect; irritant symptoms
Characterization of the degradation mechanism of polymeric scaffolds and delivery systems for regenerative medicine is essential to assess their clinical applicability. Key performance criteria include induction of a minimal, transient inflammatory response and controlled degradation to soluble non-cytotoxic breakdown products that are cleared from the body by physiological processes. Scaffolds fabricated from biodegradable poly(ester urethane)s (PEURs) undergo controlled degradation to non-cytotoxic breakdown products and support the ingrowth of new tissue in preclinical models of tissue regeneration. While previous studies have shown that PEUR scaffolds prepared from lysine-derived polyisocyanates degrade faster under in vivo compared to in vitro conditions, the degradation mechanism is not well understood. In this study, we have shown that PEUR scaffolds prepared from lysine triisocyanate (LTI) or a trimer of hexamethylene diisocyanate (HDIt) undergo hydrolytic, esterolytic, and oxidative degradation. Hydrolysis of ester bonds to yield α-hydroxy acids is the dominant mechanism in buffer, and esterolytic media modestly increase the degradation rate. While HDIt scaffolds show a modest (<20%) increase in degradation rate in oxidative medium, LTI scaffolds degrade six times faster in oxidative medium. Furthermore, the in vitro rate of degradation of LTI scaffolds in oxidative medium approximates the in vivo rate in rat excisional wounds, and histological sections show macrophages expressing myeloperoxidase at the material surface. While recent preclinical studies have underscored the potential of injectable PEUR scaffolds and delivery systems for tissue regeneration, this promising class of biomaterials has a limited regulatory history. Elucidation of the macrophage-mediated oxidative mechanism by which LTI scaffolds degrade in vivo provides key insights into the ultimate fate of these materials when injected into the body.
polyurethane; biodegradation; macrophage; oxidation; hydrolysis; scaffold