Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isocyanates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Prognosis of occupational asthma induced by isocyanates.

Several studies on the prognosis of isocyanate-induced asthma show that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work, and that further exposure to isocyanates in sensitized subjects leads almost invariably to persistence of respiratory symptoms and of bronchial hyperresponsiveness and the deterioration of airway function. Specific bronchial reactivity to isocyanates may change after cessation of work; however, some subjects continue to be sensitive to TDI several months after cessation of work. The determinants of an unfavourable prognosis for asthma seem to be the same as those for other types of occupational asthma due to low molecular weight compounds (i.e. red cedar asthma): long duration of exposure before the onset of asthma, long duration of symptoms before diagnosis, airway obstruction, and dual airway response after specific challenge tests. Also, single acute exposure to high levels of TDI in the workplace (spills) can result in persistent nonspecific bronchial hyperresponsiveness. Potential mechanisms of persistence of symptoms and of nonspecific bronchial hyperresponsiveness may be chronic inflammation, bronchial smooth muscle alteration, autonomic nervous system disregulation.

Asthma↗
PubMed1982

Antimutagenic effect of isocyanates and related compounds in Escherichia coli.

Isocyanates and isothiocyanates have been suggested to inactivate enzymes involved in the metabolic activation of chemical carcinogens and the repair of DNA damage. These compounds decrease the mutability of a tester strain of Escherichia coli B under UV irradiation. This paper deals with the antimutagenicity of acylating agents, including isocyanates and isothiocyanates, and some anti-oxidants which are suspected to be anticarcinogenic. The results can be summarized as follows. (1) The antimutagenic effect observed in the present study operates on UV-induced mutagenesis but not on X-ray-induced mutagenesis. (2) This effect operates only on the wild-type strain, H/r30R, but not on Hs30R deficient in the excision repair system. (3) This effect may function through giving the irradiated cells a greater chance to carry out excision repair by prolonging the lag-period before entry into the S-phase. (4) The carbamoylating ability of isocyanates and isothiocyanates may be responsible for the antimutagenicity, but other type of reactivities may also be involved. These antimutagens also participate in inactivating enzymes relevant to the metabolic activation of mutagens, resulting in a decrease in the frequency of chemically induced mutagenesis.

4-Nitroquinoline-1-oxide↗
PubMedDate not supplied

Work place challenge: spirometric response in polyurethane (isocyanate) paint workers.

In industrialised countries, isocyanate is probably the most common cause of occupational asthma. The present study was conducted to see the effect on FEV1 in workers who were directly exposed to isocyanate. One hundred and fourteen workers of a rail coach factory who were involved in polyurethane paint spray were studied. Spirometry was done three times, first before starting the work, at two hours and then 6-8 hours after finishing the work to see immediate, late and dual responses. Positive response was considered when there was fall of 20% or more in forced expiratory volume in 1 second (FEV1) from base line. Sixteen per cent of the workers exposed to isocyanate developed immediate reaction, 10% developed late reaction and 6% developed dual reaction. Non-smokers were more prone to develop late and dual responses.

Adolescent↗
PubMed1998

Pathomechanisms and pathophysiology of isocyanate-induced diseases--summary of present knowledge.

During recent years in Western countries, diisocyanates are one of the main causes of occupational asthma. The mechanism of diisocyanate-induced asthma is still unknown but recent evidence suggests immunological mechanisms, including cell-mediated immune responses. Immune responses to isocyanates may result in different illnesses, 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 (mutagenic and genotoxic) aspects of isocyanate disorders.

Alveolitis, Extrinsic Allergic↗
PubMed1989

(-)-(S)-flunoxaprofen and (-)-(S)-naproxen isocyanate: two new fluorescent chiral derivatizing agents for an enantiospecific determination of primary and secondary amines.

The synthesis and analytical testing of two new fluorescent chiral derivatizing agents (-)-(S)-flunoxaprofen and (-)-(S)-naproxen isocyanate, is described. In a few simple steps the free carboxylic acids [(S)-flunoxaprofen and (S)-naproxen] are activated with ethyl chloroformate/sodium azide and transformed to the corresponding isocyanates. The crystalline reaction products display high enantiomeric and chemical purity and stability. The direction of the optical rotation of both substances is inverse to that of the corresponding carboxylic acids. At ambient temperature the reagents swiftly react with primary and secondary amines, yielding highly fluorescent ureas. The applicability of the two reagents for the resolution of racemic amines was tested with a number of pharmaceuticals (antiarrhythmics, beta-adrenergic antagonists, calcium channel blockers, centrally acting antidepressants). The diastereoisomeric derivatives were efficiently resolved and separated from side-products by means of normal and reversed-phase high-performance liquid chromatography (HPLC). The use and sufficient sensitivity of the two reagents for pharmacokinetic studies were demonstrated with a determination of plasma levels of propranolol enantiomers after oral administration of the racemic drug [80 mg (R,S)-propranolol-HCl] to two volunteers.

Amines↗
PubMed1991

Inhalation toxicity of methyl isocyanate: biochemical and cytological profile of bronchoalveolar lavage fluid in rats.

Acute pulmonary injury in rats following a single inhalation exposure to methyl isocyanate (3.2 mg l-1) was reflected by alterations in the biochemical and cytological constituents of bronchoalveolar lavage fluid (BALF) over a period of 30 days. Total protein, sialic acid and lactic acid contents of BALF were increased followed by a gradual decline to normalcy between day 3 and day 30 post-exposure. The activity of lactic dehydrogenase also increased progressively with time. The cellularity of BALF was increased significantly and primarily comprised of polymorphonuclear neutrophils at 8 days. The adherence of macrophages was unchanged but their viability was lowered at 30 days post-exposure. The results indicate the significance of bronchoalveolar lavage analysis in monitoring pulmonary toxicity by methyl isocyanate, which is characterized by the hypoxic condition and reduced cellular defence. Some toxic manifestations are potentially reversible with time after cessation of exposure.

Administration, Inhalation↗
PubMedDate not supplied

Influence of methylamine and N,N'-dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity.

Subcutaneous administration of the LD50 dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats. Neither methylamine (MA) nor N,N'-dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU. Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity. The hydrolysis products of MIC had no influence on any of these parameters. Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MIC per se, in spite of its high hydrolytic instability.

Animals↗
PubMed2003

Workplace monitoring of isocyanates using ion trap liquid chromatography/tandem mass spectrometry.

A sensitive liquid chromatography/ion trap tandem mass spectrometry method was developed for the qualitative and quantitative detection of isocyanates in air. The method is based on derivatization of isocyanates with 1-(2-methoxyphenyl)piperazine during air sampling. The extracts are analyzed using an ion trap LC/MS system equipped with an electrospray (ESI) ion source. The method shows high linearity, specificity, accuracy and precision. The limits of detection are 40x to 55x lower than with UV-based methods.

Air Pollutants, Occupational↗
PubMed1992

Toxicity of the methyl isocyanate metabolite S-(N-methylcarbamoyl)GSH on mouse embryos in culture.

Methyl isocyanate, the chemical involved in the 1984 accident at Bhopal, India, forms a labile conjugate, S-(N-methylcarbamoyl)GSH (SMG), by way of a reversible reaction with GSH. We studied the toxicity of SMG on mouse embryos explanted on day 8 of gestation and cultured in rat serum for 42 hr. SMG caused concentration-dependent decreases in growth and development over the range 0.1-2 mM, without causing significant mortality. At a concentration of 2 mM, SMG completely arrested embryo development, but heartbeat was absent in only one of nine embryos at 42 hr. At a concentration of 0.25 mM, SMG reduced embryo size to 75% and protein content to 63% of the control; 18% of embryos failed to rotate. At this concentration (0.25 mM), which was selected for all other studies, spinal kinks and somite pair distortion in the region of the forelimb were evident in 38% of embryos; no other abnormalities were noted. DNA content of and thymidine incorporation by embryos and yolk sacs was reduced by SMG, although this was more pronounced in the yolk sac than in embryos. At subtoxic concentrations, the L-cysteine precursor (-)-2-oxo-4-thiazolidine-carboxylic acid did not, but GSH did, inhibit embryotoxicity of SMG. It is concluded that SMG exerts embryotoxic and dysmorphogenic effects and may contribute to systemic toxicity of methyl isocyanate.

Animals↗
PubMed1995

Phenyl isocyanate-induced asthma in rats following a 2-week exposure period.

This study was conducted to assess the toxic effects of repeated inhalation exposures to phenyl isocyanate vapor in male Wistar rats. Rats were exposed to design concentrations of 0, 1, 4, 7, or 10 mg/m3 phenyl isocyanate air for 2 weeks (6 hr/day, 5 days/week). The rats were assessed for normal toxicologic parameters, and pulmonary function tests, blood gas measurements, and analysis of bronchoalveolar lavage fluid (BALF) parameters were utilized shortly after exposures as well as 2 months postexposure. The results indicated that rats exposed to 7 and 10 mg/m3 experienced decreased body weights, hypoactivity, hypothermia, signs of respiratory tract irritation, delayed onset of mortality, and changes in organ weights. In addition, pulmonary function tests demonstrated decreased forced expiratory flow rates and quasistatic lung compliance. Arterial blood gases showed an arterial hypoxemia and changes consistent with a pronounced venous-admixture-like perfusion, suggesting severe mismatch of the ventilation/perfusion relationship. Delayed onset of mortality appeared to be associated with respiratory acidosis and hypoxemia. Biochemical and cellular components in BALF complemented the results of the functional alterations. Remarkable changes were indicated by increased activities of the BALF parameters, gamma-GPT, protein, and sialic acid. Histopathological findings provided evidence of increased secretory cell activity and a concentration-dependent increase in goblet cell hyperplasia at concentrations of 4 mg/m3 and above. In rats exposed to 7 mg/m3 further findings consisted of intraluminal inflammation of airways, hypertrophia of bronchial smooth muscle, epithelial desquamation, and eosinophilia of the airways. A complete regression of morphological lesions was not found in the animals exposed to 4 mg/m3 and above at the 2-month postexposure time period. In conclusion, the damage to the airways comprise most of the features characteristic of chronic airway inflammation or asthma.

Administration, Inhalation↗
PubMed1991

Isocyanate-induced asthma: results of inhalation tests with TDI, MDI and methacholine.

We performed diisocyanate inhalation tests (maximal concentration, 20 ppb; exposure time, 1-2 h) using toluene diisocyanate (TDI, n = 15) and diphenylmethane diisocyanate (MDI, n = 7) as well as methacholine challenges in 19 workers who had a clinical history of TDI/MDI-induced asthma. Additionally we tested volunteers who had no previous contact with diisocyanates: 10 healthy individuals with a negative methacholine test and 14 patients with asthma and a positive methacholine test were exposed to TDI. In all, 1 of the normal volunteers and 3 of the patients with asthma unrelated to diisocyanates showed a positive airway reaction to TDI, and 13 of the 19 diisocyanate workers displayed a positive result in the TDI/MDI inhalation test; however, only 6 of these 13 individuals reacted to methacholine. Furthermore, 3 of the 6 patients with a negative TDI/MDI challenge test demonstrated a significant response to methacholine. We conclude that bronchial hyperreactivity as evaluated by the methacholine challenge test is not closely related to isocyanate-induced bronchoconstriction and, therefore, the metacholine challenge is only of limited diagnostic value in patients with suspected isocyanate-induced asthma.

Asthma↗
PubMed2001

Development of a personal isocyanate sampler based on DBA derivatization on solid-phase microextraction fibers.

The design and evaluation of a portable diffusive sampler for isocyanates is described. The sampler employs dibutylamine (DBA) loaded onto 60-microm polydimethylsiloxane-divinylbenzene (PDMS-DVB) solid-phase microextraction (SPME) fibers. The DBA-isocyanate derivative is then desorbed by sonication and analyzed by LC-MS using atmospheric pressure chemical ionization (APCI). The samplers are calibrated (i.e. the uptake rate is calculated) by exposing them to a known concentration of hexamethylene diisocyanate (HDI) in a standard gas-generation chamber. The uptake rate for the proposed method, at room temperature (25 degrees C), is 1.13 pg (min ppb(v))(-1) and the method detection limit is 3.2 microg m(-3), equivalent to less than 10% of the airborne time-weighted average (TWA) exposure limits recommended by both the National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH). Practical points that should be considered when using the SPME device as a diffusive sampler are discussed.

Air Pollutants, Occupational↗
PubMed2002

Potential scans and potential energy distributions of normal vibrational modes of trichloroacetyl isocyanate.

The conformational stability and vibrational infrared and Raman spectra of trichloroacetyl isocyanate (CCl3CONCO) were investigated by ab initio MP2 and density functional B3LYP calculations using the 6-311++G** basis set. From the potential energy scans of the internal rotations in both the halomethyl and the isocyanate rotors, the molecule was predicted to exist predominantly in the cis-cis conformation. The steric hindrance between the halomethyl group and the nitrogen lone-pair was found to favor the staggered configuration for the chlorine atom, while conjugation effects favor the planar configuration for the C=O and the NCO groups. Vibrational wavenumbers were computed for the molecule at the DFT-B3LYP/6-311++G** level. Normal coordinate calculations were carried out to obtain the potential energy distributions (PED) among the symmetry coordinates of the normal modes for the molecule. The theoretical vibrational assignments were compared with experimental ones and ratios of observed to calculated wavenumbers of about 0.97-1.04 were obtained.

Isocyanates↗
PubMed1987

Pathologic changes following acute methyl isocyanate inhalation and recovery in B6C3F1 mice.

Male and female mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 91-day recovery period. Sixteen of 80 (20%) male mice in the 30-ppm group died following exposure with seven deaths occurring in the first 24 hr. Two female mice died, one each in the 30- and 10-ppm concentration groups. Five mice/sex/group were examined at 2 hr and at 1, 3, 7, 14, 28, 49, and 91 days following exposure. Treatment-related changes were restricted to the respiratory system. At 30 ppm there was extensive necrosis and erosion of the respiratory and olfactory epithelia in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Epithelialization occurred rapidly and most of the denuded turbinates were covered by flattened epithelium by Day 3. On the turbinates, recovery was essentially complete with the exception of small areas in the olfactory epithelia where lesions were present in the male mice through Day 91. In the trachea and major bronchi, fibrin and cellular debris were present in the airways, which in some cases had organized and formed intraluminal fibrotic projections. These projections became covered by respiratory epithelium. The intraluminal projections and bronchial fibrosis persisted to Day 91. In the males, where the fibrosis was more severe, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, there appeared to be complete recovery. These inhalation studies indicate that methyl isocyanate exposure of mice at or near lethal concentrations causes reversible lesions in the nose and persistent intraluminal and mural fibrosis of the major bronchi.

Administration, Inhalation↗
PubMed2004

Studies on the methyl isocyanate adducts with globin.

Isocyanates such as methylisocyanate (MIC), an intermediate in the synthesis of carbamate pesticides, or diisocyanates, used in the production of plastics, are highly reactive toxic compounds that spontaneously bind to biological macromolecules. In vivo formation of stable adducts with blood protein globin offers possibilities for biomonitoring of internal exposure to various reactive species. Thus, biomonitoring of the isocyanates through determination of their specific adducts with globin is a challenge. In this study, we characterized the adducts formed in human globin upon treatment with 100-fold molar excess of MIC. The globin was subject to enzymatic hydrolysis with pronase, and the hydrolysate was analysed by high performance liquid chromatography with positive atmospheric pressure chemical ionization mass spectrometric detection (HPLC/APCI-MS). The two major MIC adducts were those with N-terminal Val and side-chain of Lys, as confirmed by comparison with the synthetic standards. About 20 other adducts were observed, and several of them were tentatively identified using their MS and MS/MS spectra. Whereas detection of the adducts with Tyr and His was expected, the adducts with Trp and Phe, and a Lys adduct containing two MIC moieties, were probably analytical artifacts resulting from the transcarbamoylation during globin hydrolysis rather than products of direct carbamoylation. The other detected products were MIC-Val-His, derived from the N-terminal dipeptide of globin beta-chain, and dipeptides consisting of MIC-Lys attached to Gly, Val, Leu, Thr, and Glu. Failure to detect the corresponding non-modified dipeptides suggests that the pronase action may be hampered by the amino acid modification. MIC is known as a metabolic intermediate of the industrial solvents N,N-dimethylformamide (DMF) and N-methylformamide (MF) in humans and rats. The HPLC/APCI-MS analysis of globin from rats injected with DMF or MF, 1000 mg/kg, revealed the presence of the MIC adducts with both Val and Lys. The level of the Val adduct in globin from the DMF-dosed rats, determined using Edman degradation and GC/MS, was ca. 40 nmol/g, which is a level common in workers occupationally exposed to DMF. This suggests that also the Lys adduct in such human globin samples can be feasible to analysis and is therefore considered for further studies as a potential biomarker of exposure to DMF.

Animals↗
PubMed2005

Cyclization reactions of acylium and thioacylium ions with isocyanates and isothiocyanates: gas phase synthesis of 3,4-dihydro-2,4-dioxo-2H-1,3,5-oxadiazinium ions.

Gas-phase reactions of several acylium and thioacylium ions, that is H2C=N-C+=O, H2C=N-C+=S, O=C=N-C+=O, S=C=N-C+=O, H3C-C+=O, and (CH3)2N-C+=O, with both a model isocyanate and isothiocyanate, that is, C2H5-N=C=O and C2H5-N=C=S, were investigated using tandem-in-space pentaquadrupole mass spectrometry. In these reactions, the formation of mono- and double-addition products is observed concurrently with proton transfer products. The double-addition products are far more favored in reactions with ethyl isocyanate, whereas the reactions with ethyl isothiocyanate form, preferentially, either the mono-addition product or proton transfer products, or both. Retro-addition dominates the low-energy collision-induced dissociation of the mono- and double-addition products with reformation of the corresponding reactant ions. Ab initio calculations at Becke3LYP//6-311 + G(d,p) level indicate that cyclization is favored for the double-addition products and that products equivalent to those synthesized in solution, that is, of 3,4-dihydro-2,4-dioxo-2H-1,3,5-oxadiazinium ions and sulfur analogs, are formed.

Acetals↗
PubMed2005

p-Toluenesulfonyl isocyanate as a novel derivatization reagent to enhance the electrospray ionization and its application in the determination of two stereo isomers of 3-hydroxyl-7-methyl-norethynodrel in plasma.

In this paper, p-toluenesulfonyl isocyanate has been reported as a novel derivatization reagent with strong nuclephilic reactivity for the hydroxyl compounds. The derivatization for the two pharmacologically active 3-hydroxyl metabolites, 3alpha-hydroxyl-7-methyl-norethynodrel and 3beta-hydroxyl-7-methyl-norethynodrel by p-toluenesulfonyl isocyanate can be accomplished in 2 min under room temperature. The offline derivatization procedure introduced an easily ionizable sulfonylcarbamic ester moiety to the metabolites. This greatly improved the analyte's sensitivity in negative electrospray ionization and enabled us to achieve the desired lower limit of quantitation at 100 pg/ml in plasma. Therefore, a sensitive high performance liquid chromatography-mass spectrometry (HPLC-MS) method for the analysis of the two stereo isomers was developed. The method had been validated to be accurate, precise, and sensitive, and can be used for the metabolism pharmacokinetic study of tibolone in human subjects.

Chromatography, High Pressure Liquid↗
PubMed2000

Determination of 1-(2-methoxyphenyl)piperazine derivatives of isocyanates at low concentrations by temperature-programmed miniaturized liquid chromatography.

A temperature-programmed packed capillary LC method with large-volume injection on-column focusing has been developed for screening and determination of 1-(2-methoxyphenyl)piperazine derivatives of airborne toluene-2,4-diisocyanate, toluene-2,6-diisocyanate, hexamethylenediisocyanate and methylenebisphenyl-4,4-diisocyanate, based on sampling methods described in MDHS 25/3. Injection volumes up to 100 microl were successfully loaded onto the 250x0.32 mm I.D. capillary column packed with 3 microm Hypersil ODS particles. The isocyanate derivatives were loaded at 10 degrees C and eluted by a three-step temperature program starting at 10 degrees C for 10 min, followed by a temperature ramp of 2.5 degrees C min(-1) to 45 degrees C and then 9.9 degrees C min(-1) to 90 degrees C. The mobile phase consisted of acetonitrile-acetate buffer (3% triethylamine, pH 4.5) (45:55, v/v). The isocyanate derivatives were dissolved in acetonitrile-acetate buffer (3% triethylamine, pH 4.5) (30:70, v/v) to achieve sufficient focusing. The concentration limit of detection of the individual derivatives utilizing an "U" shaped flow cell with a 8.0 mm light path and an injection volume of 100 microl was 44, 87, 43 and 210 pg ml(-1) for toluene-2,6-diisocyanate, hexamethylenediisocyanate, toluene-2,4-diisocyanate and methylenebisphenyl-4,4-diisocyanate, respectively. Within the investigated concentration range, 10-500 ng ml(-1), the linear calibration curves gave correlation coefficients ranging from 0.994 to 0.998. The repeatability of the method with regard to retention time and peak height ranged from 0.3 to 1.1% and 1.1 to 2.3% (n=9) relative standard deviation, respectively. The average recovery of the method, with regard to toluene-2,4-diisocyanate, was 97.7+/-1.6% (n=9).

Chromatography, Liquid↗