PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Isocyanates”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1990

[Diagnosis of irritative-toxic isocyanate asthma with the isocyanate exposure test].

We investigated 10 healthy control subjects, 15 asthmatics without occupational exposure to isocyanate, and 45 "isocyanate workers" with workplace-related respiratory symptoms. In none of the cases did the skin test or the IgE-RAST reveal a type I sensitisation to isocyanate. The investigation programme included a lung function test, provocation with metacholine or acetylcholine, and an isocyanate challenge test under controlled clinical conditions. A total of 17 "isocyanate workers", and 1 asthma patient with no occupational exposure to isocyanate revealed a positive bronchial obstructive reaction to the isocyanate challenge test. In 10 of the patients, the MCH (ACH) test was positive; 2 were chronically obstructive, but 6 patients showed no signs of bronchial hyperreactivity. No significant differences in the severity of the bronchial obstructive reaction induced by isocyanate exposure were observed between patients with and those without bronchial hyperreactivity. In the group of "isocyanate workers", the isocyanate challenge test was observed to be superior to the MCH (ACH) provocation test in terms of sensitivity (0.68 versus 0.62) and specificity (1.0 versus 0.61), this difference being more obvious in the overall group (sensitivity 0.71 versus 0.62; specificity 0.98 versus 0.49).

Airway Resistance↗
PubMed1990

The use of an immunoassay index for antibodies against isocyanate human protein conjugates and application to human isocyanate disease.

Serum IgG and IgE to isocyanate haptenized human serum albumin (HSA) were estimated by ELISA in 55 isocyanate workers who underwent isocyanate inhalation challenge studies in Montreal, Canada. The challenges were negative in 29 workers and positive in 26 workers. Isocyanate antibodies were estimated by ELISA index. The mean IgG indices were found to be significantly higher in the challenge-positive workers, and there was a similar trend for the IgE indices. Antibody specificities for toluene diisocyanate-HSA, diphenylmethane diisocyanate-HSA, and hexamethylene diisocyanate-HSA were determined by inhibition studies with a variety of isocyanate haptenized carriers. The other isocyanate substituted carriers were either noninhibitory or caused only partial inhibition as contrasted with the complete inhibition achieved by HSA conjugated to the isocyanate to which the worker was exposed. We interpret these specificity studies as indicating that the inhalation of isocyanates results in production of antibody that recognizes new antigenic determinants that develop from the coupling of isocyanates to homologous proteins.

Antibodies↗
PubMed1990

Application of tryptamine as a derivatising agent for airborne isocyanate determination. Part 3. Evaluation of total isocyanates analysis by high-performance liquid chromatography with fluorescence and amperometric detection.

Determination of total airborne isocyanates using tryptamine as the derivatising agent was investigated. Tryptamine derivatised isocyanates were analysed by reversed-phase high-performance liquid chromatography (HPLC). The column was equipped with dual detectors of fluorescence emission and amperometric oxidation. The characteristics of fluorescence emission and amperometric oxidation of tryptamine were retained even after its reaction with isocyanates. With this unique behaviour, all tryptamine derivatised isocyanates can be quantified using HPLC by employing a single, pure derivative, such as tryptamine derivatised hexamethylene diisocyanate as the calibration standard. This is especially important for analysing polymeric isocyanates when identical calibration standards are not always available. The applicability of this method for air sampling was evaluated by comparison with the established method of Bagon et al. involving 1-(2-methoxyphenyl)piperazine. Simulation of air sampling was performed in a Test Atmosphere Generation System by the vaporisation of toluene diisocyanate. Satisfactory results were obtained, indicating the applicability of this technique for the determination of total airborne isocyanates.

Air Pollutants, Occupational↗
PubMed1989

The use of isocyanate paints in auto refinishing--a survey of isocyanate exposures and related work practices in South Australia.

A survey of 45 crash repair workshops where two-pack polyurethane spray paints are used has been carried out. Painters were interviewed using a combined health-work practice questionnaire. Monitoring for airborne isocyanate was undertaken in 14 spray shops. Health data from the questionnaire were compared with corresponding data for control groups of mechanics and industrial spray painters, not exposed to isocyanates. Compared with the other two groups, the isocyanate spray painters generally reported more respiratory and skin problems. Airborne isocyanate concentrations associated with various operations were monitored with both impinger and paper tape methods. A direct comparison of the two methods is presented.

Air Pollutants, Occupational↗
PubMed1979

Isocyanate asthma: respiratory symptoms due to 1,5-naphthylene di-isocyanate.

Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.

Adult↗
PubMed1989

Investigations on the acute toxic, cytogenetic, and embryotoxic activity of phenyl isocyanate and diethoxyphosphoryl isocyanate.

Phenyl isocyanate (I) and diethoxyphosphoryl isocyanate (II), used as intermediates in organic chemical syntheses, were tested for their acute toxic, cytogenetic, and embryotoxic activity on mice of different strains. The oral LD50 values for male CFLP mice were determined to be 196 mg/kg for I and 4080 mg/kg for II. Single oral doses of 1/40 and 1/20, respectively, of the LD50 of I (4.9 and 9.8 mg/kg) and II (102 and 204 mg/kg) did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice. After oral administration of 9.8 mg/kg I and 204 mg/kg II to pregnant Halle-AB-Jena and Halle-DBA mice at various days of gestation (4, 7, 11, or 15), none of the compounds tested were embryotoxic.

Animals↗
PubMedDate not supplied

Biotransformation of methyl isocyanate in the rat. Evidence for glutathione conjugation as a major pathway of metabolism and implications for isocyanate-mediated toxicities.

S-(N-Methylcarbamoyl)-N-acetylcysteine (AMCC), a chemically labile mercapturic acid conjugate, was identified by liquid chromatography-mass spectrometry (LC-MS) in the urine of rats dosed intraperitoneally with methyl isocyanate (MIC; 45.2 mumol). The corresponding cysteine conjugate, however, was not detected in urine. Following methylation, urine extracts were analyzed by thermospray LC-MS and the AMCC methyl ester was quantified by means of a stable isotope dilution assay procedure which utilized S-(N-methylcarbamoyl)-N-[2H3]-acetylcysteine [( 2H3]AMCC) as internal standard. The results showed that the fraction of the injected dose of MIC which appeared in 24-h urine collections as AMCC was 24.8 +/- 1.9% (mean +/- SD, N = 4). Thus, conjugation of MIC with glutathione (GSH), followed by metabolism of the resulting adduct to AMCC, appears to represent a quantitatively important pathway of biotransformation of MIC in the rat. However, in view of the known carbamoylating properties and in vitro cytotoxicity of S-linked conjugates of MIC, it seems unlikely that the GSH pathway of metabolism fulfills a conventional detoxification role in the case of MIC. In contrast, it is proposed that carbamate thioester conjugates of MIC, which can revert spontaneously to free MIC under physiological conditions, may actually contribute to the multisystem adverse effects of this highly toxic isocyanate in vivo.

Acetylcysteine↗
PubMed1992

Application of tryptamine as a derivatizing agent for the determination of airborne isocyanates. Part 5. Investigation of tryptamine-coated XAD-2 personal sampler for airborne isocyanates in workplaces.

The development of an efficient solid sorbent personal sampler with increased convenience for sample collection in workplaces is described. Several solid sorbents were coated with tryptamine, and sampling tubes were prepared with the coated sorbents. These tubes were evaluated for the collection of phenyl isocyanate vapour generated in a commercial test atmosphere generation system that permits the simultaneous collection of up to 12 uniformly loaded samples. Tryptamine-coated XAD-2 resin was shown to be the most efficient solid sorbent for the collection of airborne phenyl isocyanate. The optimum amount of tryptamine needed for coating XAD-2 resin was investigated.

Air Pollutants, Occupational↗
PubMed1989

Immunologic specificity of isocyanate-induced IgE antibodies in serum from 10 sensitized workers.

A procedure for the preparation of RAST disks used to assay isocyanate-specific IgE antibodies was developed. The outcome of the RAST was found to be strongly dependent on how the isocyanate test antigen was synthesized. Specific IgE from selected workers with isocyanate asthma reacted optimally to conjugates with less than or equal to 10 isocyanate molecules bound per molecule of human serum albumin. Further haptenization resulted in decreased specific binding and increased nonspecific binding because of high levels of total IgE. The hapten and carrier specificity of isocyanate-induced IgE antibodies were studied by direct RAST and RAST inhibition. The existence of new antigenic determinants related to both the isocyanate hapten and the carrier could be demonstrated. It was important to use a test antigen prepared from the same isocyanate as that to which the worker had been exposed, since the cross-reactivity between different isocyanate haptens was partial and varied from one patient to another. It was confirmed that isocyanate-specific IgE antibodies can be demonstrated only in a subgroup of workers with isocyanate-related bronchial asthma.

Antibody Specificity↗
PubMed1992

Workers' exposure to isocyanates.

A model of exposure to isocyanates, based on knowledge of industrial processes and starting materials and the results of industrial hygiene surveys, is proposed. This model of exposure suggests the concentration and physical form of airborne isocyanate monomers and oligomers. A new sampling and analytical system was developed that is capable of determining the physical and chemical characteristics of occupational exposure to a variety of aliphatic and aromatic isocyanates as required by the exposure model. The sampling system consisted of a dual-filter 37-mm cassette, in which the first filter captured aerosol phase contaminants and the second captured vapor phase isocyanates through derivatization with 9-(N-methylaminomethyl) anthracene (MAMA). Urea derivative recovery by the sampling system, isocyanate-MAMA reactivity, and linearity of the calibration curve were evaluated in the laboratory. The practicality of the system was evaluated during field trials. Sampling times are reduced to 15 min, and the detection limit for TDI, HDI, and MDI was 1.0 micrograms/m3. A partial validation of the new sampling system was performed for HDI vapor by comparison to a standard method in field trials and for TDI vapor in a controlled test atmosphere. The analytical system may also be used to measure the concentration of oligomeric isocyanates. Airborne concentrations of isocyanates were measured in two foam plants, nine paint shops, and two foundries to verify the usefulness of the model. Exposure in foam plants was predominantly to gaseous monomeric isocyanates. Exposure to oligomer isocyanates was higher than expected in paint shops. Both monomer and oligomer isocyanates were undetectable in foundries.

Air Pollutants, Occupational↗
PubMed1975

Inhibition of rat liver DNA polymerase by nitrosoureas and isocyanates.

The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexl-1-nitrosourea, and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea on two nonmitochondrial DNA polymerases (I and II) purified from rat liver and hepatoma were examined. The activity of DNA polymerase I was not altered by treatment with any of the nitrosoureas or the corresponding isocyanates, 2-chloroethyl isocyanate and cyclohexyl isocyanate. Incubation of DNA polymerase II with the nitrosoureas (1 mM) inhibited its enzymatic activity 30 to 45%. DNA polymerase II was inhibited 75 and 90% by 1.mM 2-chloroethyl isocyanate and cyclohexyl isocyanate, respectively. The nitrosoureas appear to exert their inhabitory action on the enzyme (DNA polymerase II) rather than on the DNA template. Pretreatment of the enzyme increased the degree of inhibition by 1 mM nitrosourea (50 to 60% inhibition) or 2-chloroethul isocyanate (greater than 90% inhibition), whereas pretreatment of the DNA template did not enhance the inhibitory effect. The three nitrosoureas are equally effective as inhibitors of DNA polymerase II. 2-Chloroethyl isocyanate and cyclohexyl isocyanate are better inhibitors than are the nitrosoureas. Since further decomposition products of the isocyanates, 2-chloroethylamine and cyclohexylamine, do not inhibit DNA polymerase II, we conclude that the isocyanates, which are decomposition products of the nitrosoureas, are the active inhibitors of the enzyme.

Animals↗
PubMed1989

Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.

Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.

Adult↗
PubMed1977

Active site specific inactivation of chymotrypsin by cyclohexyl isocyanate formed during degradation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

Prolonged incubation of 1-(2-chloroethyl)-3-([1-14C]cyclohexyl)-1-nitrosourea with chymotrypsin resulted in covalent modification and concomitant inactivation of chymotrypsin via degradation of the nitrosourea to form cyclohexyl isocyanate. Cyclohexyl isocyanate was shown to be an active-site-specific inactivator of chymotrypsin. A cyclohexyl isocyanate to enzyme molar ratio of 0.63 was required to produce 50% enzyme inactivation, thus demonstrating the high specificity of inactivation. At 2.38 X 10(-4) M chymotrypsin this near stoichiometric inactivation was not significantly affected by the presence of 1, 5, and 10 mM L-lysine. Degradation of an excess of 1-(2-chloroethyl)-3-([1-14C]-cyclohexyl)-1-nitrosourea in the presence of enzyme yielded 1.11 +/- 0.07 mol of covalently bound [14C]cyclohexyl moiety per mol of enzyme inactivated. Short-term incubation demonstrated that the nitrosourea neither inhibited nor protected the enzyme from cyclohexyl isocyanate inactivation. Treatment of chymotrypsin with less than stoichiometric amounts of cyclohexyl isocyanate or titration of the active-site serine with phenylmethanesulfonyl fluoride followed by in situ degradation of excess 1-(2-chloroethyl)-3-([1-14C]cyclohexyl)-1-nitrosourea resulted in a decreased amount of covalently bound 14C proportional to the extent of inactivation by these reagents prior to 14C labeling. These results strongly suggest that cyclohexyl isocyanate, whether added directly or generated by CCNU degradation, reacted almost exclusively with the active site of the enzyme. The extent of this inactivation indicates that 70% of the CCNU degraded in such a manner as to form cyclohexyl isocyanate.

Binding Sites↗
PubMed1989

Isocyanate exposure and hypersensitivity pneumonitis--report of a probable case and prevalence of specific immunoglobulin G antibodies among exposed individuals.

A car painter experienced three episodes of a hypersensitivity pneumonitis-like disease after exposure to two-component acrylic lacquers with hexamethylene diisocyanate (HDI) as the curing agent. High titers of HDI-specific immunoglobulin (Ig) G antibodies were found in the patient's serum by means of enzyme-linked immunosorbent assay (ELISA). In the ELISA, 5 to 10% of the sera from 455 isocyanate-exposed but asymptomatic workers were positive, depending on the criterion used for a positive test, whereas 0% of the sera from 157 unexposed referents was found to be positive. Among 10 subjects with isocyanate-induced asthma and isocyanate-specific IgE antibodies, 50% had specific IgG. It was concluded that the presence of isocyanate-specific IgG antibodies in serum is correlated with isocyanate exposure rather than with symptoms of isocyanate-induced disease.

Adult↗
PubMed1992

Closed-circuit methodology for inhalation challenge tests with isocyanates.

The diagnosis of isocyanate-induced occupational asthma can be made by exposing subjects to isocyanates in small challenge rooms. There are, however, several pitfalls inherent in this procedure. Isocyanate concentrations may not remain stable throughout the exposure and may exceed the recommended TLV ceiling of 20 ppb. This can induce irritant or unduly severe bronchial reactions. To overcome these problems, a closed-circuit apparatus for generating isocyanates in a gaseous form was developed; it was assessed in 20 subjects suspected of having isocyanate-induced asthma. Subjects were tested using both the small challenge room method and the new closed-circuit method in a randomized sequential way. Isocyanate concentrations were more stable with the closed-circuit apparatus than with the challenge room method (mean of individual variance of 6.3 and 61.8, respectively; p less than 0.001). The percentage of the total exposure time during which concentrations were above 20 ppb was reduced from 11.3 to 4.5% (p less than 0.001). The two methods yielded the same number of positive and negative responses, except for one subject who did not have a positive reaction when tested with the challenge room method. The pattern and magnitude of asthmatic reactions were similar for both methods. However, the duration of exposure was shorter with the challenge room method than with the closed-circuit methods (p = 0.04).

Administration, Inhalation↗
PubMed1988

Occupational asthma due to isocyanates.

162 subjects who had been exposed to isocyanates, who had developed symptoms during the exposure period, or in the evening or night and, therefore, had a history compatible with isocyanate-induced asthma, were studied with inhalation challenge testing to isocyanates (toluene diisocyanate and methylene diphenyl diisocyanate) and methacholine, because they were suspected of having occupational asthma. None of these subjects had symptomatic asthma before employment. The diagnosis of occupational asthma was delayed (duration of symptoms before diagnosis: 3.9 +/- 0.4 yrs). Isocyanate-asthma documented by a positive inhalation challenge to isocyanates was present in 57.4% of the subjects. A higher degree of airway responsiveness to methacholine was present in subjects with a positive isocyanate inhalation challenge compared to subjects with a negative challenge (Gmean and GESM: 0.407 (1.14) vs 0.942 (1.14) mg). The majority of the subjects complained of shortness of breath and cough. The low proportion of atopic subjects (21.5%) and of smokers (7.5%), and the high proportion of subjects with the late component in the asthmatic reaction (71%) appear to be common features in this disease.

Adult↗
PubMed1990

S-(N-methylcarbamoyl)glutathione: a reactive S-linked metabolite of methyl isocyanate.

S-(N-methylcarbamoyl)glutathione, a chemically-reactive glutathione conjugate, has been isolated from the bile of rats administered methyl isocyanate and characterized, as its N-benzyloxycarbonyl dimethylester derivative, by tandem mass spectrometry. The ability of this glutathione adduct to donate an N-methylcarbamoyl moiety to the free -SH group of cysteine was evaluated in vitro with the aid of a highly specific thermospray LC/MS assay procedure. The glutathione adduct reacted readily with cysteine in buffered aqueous media (pH 7.4, 37 degrees C) and after 2 hr, 42.5% of the substrate existed in the form of S-(N-methylcarbamoyl)cysteine. The reverse reaction, i.e. between the cysteine adduct and free glutathione, also took place readily under these conditions. It is concluded that conjugation of methyl isocyanate with glutathione in vivo affords a reactive S-linked product which displays the potential to carbamoylate nucleophilic amino acids. The various systemic toxicities associated with exposure of animals or humans to methyl isocyanate could therefore be due to release of the isocyanate from its glutathione conjugate, which thus may serve as a vehicle for the transport of methyl isocyanate in vivo.

Animals↗