| 1. |
- Johannesson, Gunvor, et al.
(author)
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Serum albumins are the major site for in vivo formation of hapten-carrier protein adducts in plasma from humans and guinea-pigs exposed to type-1 allergy inducing hexahydrophthalic anhydride
- 2001
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In: Clinical and Experimental Allergy. - 1365-2222. ; 31:7, s. 1021-1030
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Journal article (peer-reviewed)abstract
- BACKGROUND: Organic acid anhydrides (OAAs) are highly allergenic compounds used in the chemical industry. The OAAs probably act as haptens but the proteins that form conjugates with OAAs in vivo are still unknown. Conjugates between the anhydrides and serum albumins (SAs) have routinely been used when testing for OAA-specific antibodies. However, the use of SA as the carrier-protein in these tests has never been evaluated. OBJECTIVE: The aim of this study was to identify major and also immunologically relevant protein conjugates of a particularly sensitizing OAA, hexahydrophthalic anhydride (HHPA), in plasma. METHODS: Plasma was obtained from a HHPA-exposed worker, from a guinea-pig (GP) exposed to HHPA in an exposure chamber for 2 weeks (8 h/day, 5 days/week) and from a GP exposed once, nose-only, to tritium-labelled HHPA for 8 h. The plasma was fractionated using ion exchange chromatography and gel filtration. These fractions and also aliquots of unfractioned plasma were hydrolysed, derivatized and analysed for anhydride adduct content using gas chromatography-mass spectrometry. Further, plasma from the tritium labelled HHPA-exposed GP was separated by SDS gel electrophoresis and analysed by autoradiography. In addition, immunologically relevant proteins were identified through specific IgE and IgG immunoblottings using sera from exposed workers. RESULTS: For humans > 85% and for GPs > 74% of the HHPA-adducts coeluted with SA in plasma. Autoradiography of GP-plasma shows a single 66 kDa protein that binds HHPA. IgE immunoblotting shows a major 66 kDa and a minor 28 kDa protein which could be inhibited by HHPA-SA conjugate. IgG immunoblotting showed a major 66 kDa protein and several minor protein bands. CONCLUSION: This study shows SA to be the major protein in plasma that forms adducts in vivo with HHPA. The results also show that in an in vitro synthesized HHPA plasma protein conjugate, HHPA-specific IgE and IgG antibodies bind preferably to the SA.
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| 2. |
- Jönsson, Bo A, et al.
(author)
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Determination of cyclic organic acid anhydrides in air using gas chromatography .2. Sampling and determination of hexahydrophthalic anhydride, methylhexahydrophthalic anhydride, tetrahydrophthalic anhydride and octenylsuccinic anhydride
- 1996
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In: Analyst. - 1364-5528. ; 121:9, s. 1285-1290
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Journal article (peer-reviewed)abstract
- Methods for sampling and determination of four organic acid anhydrides are described. The methods were validated in a standard atmosphere and in the work environment. Hexahydrophthalic anhydride (HHPA), methylhexahydrophthalic anhydride (MHHPA), tetrahydrophthalic anhydride (THPA) and octenylsuccinic anhydride (OSA) were sampled using Tenax and Amberlite XAD-2 solid sorbents and determined by GC with flame ionization detection (FID) after elution. The precision was normally better than 10% but for OSA it was up to 19%. The detection limits were 0.1 µg per sample. MHHPA, THPA and OSA were also sampled using bubblers containing aqueous sampling solutions. MHHPA and THPA was derivatized with pentafluorobenzyl bromide (PFBBr) and determined by GC with MS detection. OSA was derivatized by methanol with boron trifluoride catalysis and determined by GC–FID. The precisions for MHHPA and THPA were 4 and 8%, respectively, and the detection limit was < 0.005 µg per sample. The precision for OSA was up to 58% and the detection limit was 0.2 µg per sample. HHPA and MHHPA were also sampled on glass-fibre filters, derivatized with PFBBr, and determined by GC–MS with good results. However, further validations of the filter methods are needed.
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| 3. |
- Lindh, Christian, et al.
(author)
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Binding of the potent allergen hexahydrophthalic anhydride in the mucosa of the upper respiratory and alimentary tract following single inhalation exposures in guinea pigs and rats
- 1999
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In: Toxicology. - 0300-483X. ; 134:2-3, s. 153-168
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Journal article (peer-reviewed)abstract
- Hexahydrophthalic anhydride (HHPA; CAS No. 13149-00-3) is a highly allergenic compound commonly used in the chemical industry. Guinea pigs and rats were exposed to [3H2]HHPA by inhalation for 3-8 h and were killed at various intervals during 7 days. The tissue distribution of non-volatile and covalently bound radioactivity was studied by autoradiography. Tissue bound radioactivity was mainly found in the mucosa of the upper respiratory airways, whereas negligible levels were observed in the lungs. In addition, tissue bound radioactivity was present in the gastrointestinal tract and conjunctiva. Moreover, in the cortex of the kidneys in rats, but not in guinea pigs, a low level of tissue bound radioactivity was found. The radioactivity in the tissues persisted for at least 7 days after the end of exposure. Plasma proteins and soluble proteins from trachea, lung, and kidney from [3H2]HHPA-exposed animals were separated by gel filtration. The radioactivity in dialysed plasma was mainly found in the same fractions as albumin. The soluble proteins from trachea, lung, and kidney in both rats and guinea pigs showed a similar pattern as found in blood. The radioactivity in dialysed plasma from both guinea pigs and rats seemed to decay according to a two-compartment model. The non-extractable binding of [3H2]HHPA in the upper respiratory airways and conjunctiva may be of relevance for symptoms in workers with allergy, since they mainly develop symptoms and signs from the nose and eyes.
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| 4. |
- Lindh, Christian, et al.
(author)
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Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers
- 1997
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 70:2, s. 128-132
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). METHODS: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. RESULTS: The time-weighted average (TWA) air levels ranged from 5 to 60 micrograms MHHPA/m3 during 8-h workshifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 micrograms MHHPA/m3 corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. CONCLUSION: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA.
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| 5. |
- Lindh, Christian, et al.
(author)
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Biological monitoring of toluene diisocyanate (TDI) exposure by analysis of urine from exposed workers
- 2002
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In: Proceedings 50th ASMS Conference on Mass Spectrmetry and Allied Topics. ; , s. 655-656
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Conference paper (peer-reviewed)abstract
- A gas chromatography-negative ion chemical ionization-selected ion monitoring-mass spectrometry (GC-NICI-SIM-MS) method was used to quantitate the metabolite toluene diamine (TDA) in urine samples of toluene diisocyanate (TDI) exposed workers. In order to validate the biological monitoring method, air samples were collected and analyzed using a liquid chromatography tandem mass spectrometry (LC-MS) method. The urine samples were treated with liquid-liquid extraction to retrieve the toluene diamine (TDA). It was observed that urinary TDA levels were applicable fro biological monitoring of TDI exposure.
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| 6. |
- Lindh, Christian, et al.
(author)
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Direct measurement of hexahydrophthalic anhydride in workplace air with a transportable Fourier transform infrared spectrometer
- 1996
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In: American Industrial Hygiene Association Journal. - : Informa UK Limited. - 0002-8894. ; 57:9, s. 832-836
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Journal article (peer-reviewed)abstract
- A method for direct measurement of hexahydrophthalic anhydride (HHPA) in workplace air by use of a Fourier transform infrared (FTIR) spectrometer was developed. Two visits were made to a plant manufacturing capacitors where HHPA was used. On the first visit a calibration method was developed according to what was expected to give the best calibration. This was performed by collection of 82 FTIR spectra from the air while simultaneously taking samples with a reference method using Amberlite XAD-2 sorbent tubes. On the second visit, two weeks later, the calibration method was used for prediction of HHPA concentrations (n = 52) in air; these were compared with XAD-2 determinations. The predicted FTIR values as a function of the XAD-2 determinations were used to evaluate some parameters regarding the FTIR method. The limit of detection was 120 micrograms HHPA/m3, and the precision at 150 micrograms/m3 was 22% and at 400 micrograms/m3 8%. When sampling from a pure HHPA atmosphere the obtained concentration by the FTIR was 103% of that of the XAD-2 tubes. The selection of different analytical parameters for the determinations are also discussed. The method is a useful tool in fast mappings of exposure levels.
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| 7. |
- Rosqvist, Seema, et al.
(author)
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Exposure-response relationships for hexahydrophthalic and methylhexahydrophthalic anhydrides with total plasma protein adducts as biomarkers.
- 2003
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In: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 29:4, s. 297-303
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study investigated the exposure-response relationships of hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) and evaluated the applicability of the total plasma protein adducts (TPPA) of these anhydrides as biomarkers of exposure and risk. METHODS: In a cross-sectional study of 139 workers in a plant manufacturing electrical capacitors, the long-term exposure to HHPA and MHHPA was assessed through the quantification of TPPA using gas chromatography-mass spectrometry. Smoking and medical histories were obtained through questionnaires. Work-related symptoms of the eyes and airways were recorded. Specific immunoglobulin (Ig) E (radioallergosorbent test) and IgG (enzyme-linked immunosorbent assay) were determined in serum. RESULTS: The mean level of the TPPA of HHPA was 840 fmol/ml and that of the TPPA of MHHPA was 1700 fmol/ml. There was no correlation between the TPPA of HHPA and the TPPA of MHHPA. Of all the workers, 19% were found to be positive for specific IgE and 17-19% for IgG. Positive associations were observed between HHPA exposure and specific IgE and IgG and between MHHPA exposure and specific IgG. Regarding work-related symptoms, 27% of the workers had symptoms of the nose, 21% had symptoms of the eyes, 11% had symptoms of the lower airways, and 8% had nose bleeding. There were significant exposure-response relationships for symptoms of the eyes and nose for HHPA exposure. CONCLUSIONS: The results show that there is an exposure-response relationship for HHPA both with specific antibodies and with work-related symptoms and down to adduct levels of 40 fmol/ml plasma. In addition, the results elucidate the potential power of TPPA as a relevant index of exposure and risk.
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| 8. |
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| 9. |
- Sennbro, Carl Johan, et al.
(author)
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Biological monitoring of exposure to toluene diisocyanate.
- 2004
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In: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 30:5, s. 371-378
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Journal article (peer-reviewed)abstract
- OBJECTIVES :Toluene diisocyanate (TDI) is used in the manufacture of polyurethane and is a potent inducer of diseases of the airways. In this study, 2,4- and 2,6-toluenediamine in hydrolyzed urine and plasma were evaluated as biomarkers of exposure to 2,4- and 2,6-TDI, respectively. METHODS: For 81 exposed workers from nine different plants, the personal 8-hour time-weighted-average exposure to TDI was monitored by a filter method with 1-(2-methoxyphenyl)piperazine. In parallel, urinary samples (U1) were collected during the last 4 hours of the workshift. On a different occasion, blood samples and additional urinary samples (U2) were collected from the exposed workers, and also from a reference group consisting of 121 unexposed workers. The biomarker levels were determined in urine and plasma by the use of alkaline hydrolysis. RESULTS: There were strong associations between the personal air and biomarker levels, with correlation coefficients in the range of 0.75-0.88 for the U1 samples and in the range of 0.50-0.78 for the plasma samples. By weighted linear regression, the relations were calculated between the air and biomarker levels. The slopes of the obtained regression curves ranged from 1.8 to 2.7 m3/1 for air-urine and from 2.2 to 2.9 m3/1 for air-plasma, and the intercepts were all close to the origin of the coordinates. Through the extrapolation of these regression curves, biological exposure limits were calculated. CONCLUSIONS: The biological monitoring methods and strategies presented in this report are useful for assessing exposure to TDI in practice.
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| 10. |
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