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 271 records · Page 15Linked to original sources

Can We protect workers from developing the adverse respiratory effects of isocyanate exposure?

In this review, the authors have attempted to present the difficulty in defining a permissible exposure limit (PEL) to agents that act as sensitizers and may induce asthma-even at exposure levels less than the PEL. One approach to this relatively unaddressed problem may be to define the separate aspects of exposure to the specific sensitizing agent. The first effect is an accelerated rate of decline in lung function in nonsensitized individuals who are exposed to the agent (in this case the model used is isocyanates). The second effect is sensitization. Rules for developing a PEL might take this sensitizing effect into account, and this group of agents with such dual effects may be defined as "sensitizers." Exposure to agents with this designation would require special educational and surveillance initiatives to facilitate early detection. The elimination of sensitization may be a greater challenge. An important form of prevention is medical screening of exposed workers, yet it is unclear which screening approach best identifies workers with early isocyanate asthma.

Asthma↗

Monitoring of haemoglobin-methyl isocyanate adduct by high-performance liquid chromatography with diode array detector.

Carbamylation of haemoglobin by methyl isocyanate (MIC) was detected by high-performance liquid chromatography (HPLC) using a photodiode array detector following cyclisation of the N-terminal valine into methyl isopropyl hydantoin (MIH). MIH was also synthesised by reaction of MIC with valine, the chromatographic conditions standardised and the spectrum derived by a photodiode array detector recorded for confirmation of the identity of MIH. This HPLC method is specific, sensitive and suitable for the detection of exposure of blood samples to methyl isocyanate.

Accidents↗

[A case of hypersensitivity pneumonitis due to isocyanate (TDI)].

A 46-year-old man who had worked in a paint processing plast for over 29 years was admitted to our hospital with complaints of nocturnal dyspnea and dry cough. A chest X-ray film showed diffuse granular shadows in bilateral lungs. Pulmonary function tests revealed reduction of diffusing capacity and restrictive impairments. Hypersensitivity pneumonitis (HP) due to isocyanates was speculated from his occupational history and clinical course. Positive skin tests against TDI-HSA and MDI-HSA, precipitating antibody against TDI-HSA, and negative lymphocyte stimulating tests of peripheral blood and bronchoalveolar lavage fluid were also noticed. Environmental provocation test was positive. Histological findings of transbronchial lung biopsy specimens showed diffuse alveolitis and Masson body, but no granulomas. According to these results, the patient was diagnosed as HP due to TDI. Type III allergy of Gell-Coombs seems to participate in this case. The granulomatous lesion is seen less frequently in isocyanate-related HP than in HP induced by organic dusts, which suggests the difference in immunological and histological reactions between both types of HP.

Alveolitis, Extrinsic Allergic↗

[Application of Pirkle-type chiral column to the resolution of enantiomeric drugs: resolution and identification of alpha-naphthyl isocyanate derivatives of alprenolol and some other beta-blockers].

alpha-Naphthyl isocyanate (NI) as a derivatizing agent to separate several beta-blockers was described. This procedure is simple, rapid and gives good resolution. Experiments with NI derivatives of alprenolol showed that the isocyanate group reacted with the amino group on the analyte to form urea under mild conditions and with the hydroxyl group to form carbamate under relatively vigorous conditions. The results also indicated that the derivatized reactions is 1:1 between NT and analytes.

Adrenergic beta-Antagonists↗

A 10-year follow-up study of a group of workers exposed to isocyanates.

The ventilatory capacity of 68 workers who were exposed to isocyanates was determined. Forty-two of the workers had been studied in 1971. The overall ventilatory capacity of the subjects fell within the predicted range except that two subjects, both of whom were smokers, had minimal obstruction. No significant shift decrement was noted in any of the subjects. There was no evidence to suggest that an excess decrement in ventilatory capacity occurred during the period of observation; however, exposure to isocyanates had been well within the then-extant time-weighted average.

Adult↗

The antibody response to methyl isocyanate: experimental and clinical findings.

Sera from 99 subjects exposed to the industrial gas leak in Bhopal on December 2, 1984 were studied along with sera from guinea pigs exposed to methyl isocyanate (MIC) to determine the production of antibodies specific to (MIC). Each of the four guinea pigs injected with the reactive isocyanate produced MIC-specific antibodies in titres of 1:5120 to 1:10240, when tested with MIC-guinea pig albumin antigen conjugate. Analogous antigens prepared by reaction of MIC with human serum albumin were used to probe production of antibodies in 264 serially obtained human sera from 99 subjects from Bhopal. MIC-specific antibodies belonging to IgG, IgM and IgE classes were detected in eleven subjects. Though titres were low and transient (declining after several months) these findings indicate that the single large exposure to MIC resulted in an immunologic response. This finding was concomitant with chronic respiratory effects following MIC exposure.

Accidents, Occupational↗

Dibutyltin oxide--phenyl isocyanate system for regioselective phenylcarbamoylation of the hydroxy-groups of ribonucleosides.

For partial phenylcarbamoylation of the hydroxy-groups of ribonucleosides, dibutyltin oxide--phenyl isocyanate system was found to be surperior to the bis(tributyltin) oxide--phenyl isocyanate system from the standpoint of reaction procedures including isolation of the products; the reaction was proved to occur with similar regioselectivity and to give the corresponding 5'-, 3'-, and 2'-O-phenylcarbamoyl derivatives in good yields, respectively, due to the conditions used.

Cyanates↗

Zirconocene-mediated intermolecular coupling of Si-tethered diynes with alkynes, ketones, aldehydes, and isocyanates by means of novel skeletal rearrangement of zirconacyclobutene-silacyclobutene and zirconacyclohexadiene-silacyclobutene fused-ring intermediates.

Bis(alkynyl)silanes react with low valent zirconocene species to afford zirconacyclobutene intermediates. These in situ generated reactive organometallic intermediates can react with alkynes, ketones, aldehydes, and isocyanates by means of a novel skeletal rearrangement. When a zirconacyclobutene intermediate was treated with an alkyne, an alpha-alkynylsilyl zirconacyclopentadiene was formed. Addition of dimethyl acetylenedicarboxylate (DMAD) and CuCl resulted in one-pot formation of an alkynylsilyl-benzene derivative from three different alkynes. At a higher temperature, the alpha-alkynylsilylzirconacyclopentadiene was transformed by means of an intramolecular skeletal rearrangement to a zirconacyclohexadiene-silacyclobutene fused-ring compound, which reacted with DMAD in the presence of CuCl affording the same alkynylsilyl-benzene derivative. When treated with a ketone, an aldehdye, or an isocyanate, the zirconocyclobutene intermediate also underwent the above-mentioned skeletal rearrangement, generating zirconocene-mediated cross-coupling products.

Journal Article↗

Occurrence and specificity of IgE antibodies to isocyanates in occupationally exposed workers.

The levels of IgE antibodies specific for toluene-diisocyanate (TDI), diphenylmethane-diisocyanate (MDI) and hexamethylene-diisocyanate (HDI) were determined in eight workers with an unequivocal history of professional asthma, all having been exposed to isocyanates in the working atmosphere. Five workers were examined at the clinical onset of asthma. They had serum IgE antibodies specific for TDI, MDI and HDI, and depressed pulmonary ventilation parameters. In contrast, three workers, who had only a mild bronchial obstruction at the time of testing, had no anti-isocyanate IgE antibodies. The results indicated that asthma was induced by type I allergic reaction, but other pathogenetic mechanisms of bronchoobstruction could not be completely ruled out.

Adult↗

New aspects of isocyanate asthma.

Air concentration of isocyanates are associated with the frequency of induced diseases. Asthma, bronchitis and rhinitis, chronic obstructive lung disease, and allergic alveolitis, respectively, were observed in exposed workers. Inhalation challenge tests with isocyanates found some 14% of symptomatic persons immunologically sensitized. At and above current threshold limit values (10 ppb) there is a risk of lung function deterioration also in asymptomatic workers.

Air Pollutants, Occupational↗

The role of isocyanates in the toxicity of antitumour haloalkylnitrosoureas.

The cytotoxicity of the antitumour nitrosoureas BCNU and CCNU and the isocyanates which they liberate (chloroethylisocyanate and cyclohexylisocyanate respectively) has been measured utilising an in vitro-in vivo bioassay. Lines of the TLX5 lymphoma and L1210 leukaemia were used which were either sensitive or resistant to nitrosoureas in vivo. An estimated logarithmic cell kill produced by each compound in vitro (before injecting the cells into animals) was calculated by reference to assays of the survival time of animals given from 2 X 10(5) to 2 X 10(0) cells of each line. Resistance to both BCNU and CCNU was observed in vitro in the cell lines of the TLX5 lymphoma made resistant to either BCNU or a dimethyltriazene in vivo. The latter tumour was cross-resistant in vivo to nitrosoureas. Resistance in vitro to nitrosoureas was also observed in a line of L1210 leukaemia which had had resistance to BCNU induced in vivo. The nitrosourea resistant TLX5 lymphomas were cross-resistant in vitro to both cyclohexylisocyanate and chloroethylisocyanate whereas the nitrosourea resistant L1210 line showed no cross-resistance to cyclohexylisocyanate and marginal cross-resistance to chloroethylisocyanate. The results suggest that the TLX5 lymphoma, which is naturally resistant to alkylating agents of the 2-chloroethylamine type, may be sensitive to in vivo to nitrosoureas as a consequence of the intracellular release of isocyanates. This hypothesis was supported by the finding that the resistant TLX5 lymphoma showed no cross-resistance to other electrophilic agents, for example formaldehyde, monomethyltriazene or HN2. The transport of nitrosoureas into the sensitive and resistant cell lines was similar in profile and there was no difference in the concentration of non-protein thiols.

Animals↗

Outcome of asthma induced by isocyanates.

Isocyanates are widely used in industry for the manufacture of polyurethanes. Although they are recognized as an important cause of occupational asthma, it is unclear whether asthma persists after avoidance of exposure. We have followed up 50 cases, all of whom had avoided exposure for at least 4 years. At follow-up, 82% continued to have respiratory symptoms and approximately half of these required treatment at least once per week. These results indicate that a significant proportion of those with isocyanate-induced asthma are likely to have persisting symptoms for at least several years after exposure is avoided.

Adult↗

Chip-based on-line nanospray MS method enabling study of the kinetics of isocyanate derivatization reactions.

The reaction of propyl isocyanate (2), benzyl isocyanate (3), and toluene-2,4-diisocyanate (4) with 4-nitro-7-piperazino-2,1,3-benzoxadiazole (1) to yield the corresponding urea derivatives 5 was carried out in a continuous flow glass microfluidics chip. Real-time monitoring of the derivatization reactions was done by electrospray ionization mass spectrometry, making use of a recently reported modular chip-MS interface. Rate constants of 1.5 x 10(4), 5.2 x 10(4), and 2.4 x 10(4) M(-1) min(-1) were determined for 2, 3, and 4, respectively. Using macroscale batch conditions, the rate constants are 3-4 times lower. The faster on-chip kinetics is attributed to the more efficient molecular diffusion in the micrometer-sized channel.

Journal Article↗

Alkyl isocyanates as active site-specific reagents for serine proteases. Location of alkyl binding site in chymotrypsin by X-ray diffraction.

The structure of octylcarbamoyl-alpha-chymotrypsin to a resolution of 3.0 A is described. The n-octyl side chain of the active site directed irreversible inactivator octyl isocyanate is bound exclusively in the hydrophobic substrate binding pocket. The n-octyl isocyanate forms a planar urethane bond with the Ser-195 Ogamma and extends approximately 1 A deeper into the hydrophobic pocket than the indolyl group of indoleacryloyl-alpha-chymotrypsin (Henderson, R. (1970), J. Mol. Biol. 54, 341). All the structural changes are essentially identical with those observed in indoleacryloyl-alpha-chymotrypsin including the observation of a hydrogen bonded water molecule between the carbonyl oxygen of the octylcarbamoyl group and the imidazole group of His-57. The observed mode of n-octyl alkyl binding to chymotrypsin is consistent with the hypothesis proposed earlier (Brown, W. E. and Wold, F. (1973), Biochemistry 12, 828).

Binding Sites↗

Reactivity of organolanthanide and organolithium complexes containing the guanidinate ligands toward isocyanate or carbodiimide: synthesis and crystal structures.

The direct reactions of (C5H5)2LnCl with LiN=C(NMe2)2 proceeded at room temperature in THF under pure nitrogen to yield the lanthanocene guanidinate complexes [(C5H5)2Ln(mu-eta1:eta2-N=C(NMe2)2)]2 (Ln = Gd (1), Er (2)). Treatment of phenyl isocyanate with complexes 1 and 2 results in monoinsertion of phenyl isocyanate into the Ln-N(mu-Gua) bond to yield the corresponding insertion products [(C5H5)2Ln(mu-eta1:eta2-OC(N=C(NMe2)2)NPh)]2 (Ln = Gd (3), Er (4)), presenting the first example of unsaturated organic small molecule insertion into the metal-guanidinate ligand bond. Further investigations indicate that N,N'-diisopropylcarbodiimide does not react with complexes 1 and 2 under the same conditions; however, it readily inserts into the lithium-guanidinate ligand bond of LiN=C(NMe2)2. As a synthon of the insertion product Li[(iPrN)2C(N=C(NMe2)2)], its reaction with (C5H5)2LnCl gives the novel organolanthanide complexes containing the guanidinoacetamidinate ligand, (C5H5)2Ln[(iPrN)2C(N=C(NMe2)2)] (Ln = Yb (5), Er (6), Dy (7)). All complexes were characterized by elemental analysis and spectroscopic properties. The structures of complexes 1, 3, 5 and 7 were determined through X-ray single-crystal diffraction analysis.

Journal Article↗

First structurally characterized actinide isocyanates.

The synthesis and characterization of the neutral uranylisocyanate UO(2)(NCO)(2)(OP(NMe(2))(3))(2) [crystal data: monoclinic, P2(1)/c, a = 8.512(2) A, b = 10.931(2) A, c = 14.329(3) A, beta = 103.923(3) degrees , V = 1294.0(4) A(3), Z = 2] and isocyanato uranate (Et(4)N)(6)[(UO(2))(2)(NCO)(5)O](2) x 2CH(3)CN x H(2)O [crystal data: monoclinic, P2(1)/c, a = 17.2787(2) A, b = 15.560(1) A, c = 32.7619(4) A, beta = 94.0849(5) degrees , V = 8786.5(2) A(3), Z = 4] are reported. Not only are these compounds the first unambiguously characterized uranium isocyanates regardless of the oxidation state for uranium, but they are also the first structurally characterized actinide isocyanates. Both compounds show coordination of the OCN moiety through nitrogen to uranium and were characterized using IR and (1)H, (13)C, (14)N, and (31)P NMR spectroscopy and X-ray diffraction.

Journal Article↗

Nitrosyl isocyanate (ONNCO): gas-phase generation and a HeI photoelectron spectroscopy study.

The nitrosyl isocyanate (ONNCO) has been generated from a heterogeneous reaction of gaseous nitrosyl chloride with silver isocyanate and studied for the first time in the gas phase. This structurally and energetically novel transient specimen is characterized by HeI photoelectron spectroscopy combined with DFT calculations. Both the calculations and the spectroscopic results suggest that the molecule adopts an open-chain trans structure. The observed decomposition products indicate the formation of ONNCO and further confirm the previously reported decomposition pathway.

Journal Article↗