| 1. |
- Jönsson, Bo A, et al.
(författare)
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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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Ingår i: Analyst. - 1364-5528. ; 121:9, s. 1285-1290
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Jönsson, Bo A, et al.
(författare)
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Determination of hexahydrophthalic and methylhexahydrophthalic acids in urine by gas chromatography-negative-ion chemical-ionisation mass spectrometry
- 1996
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Ingår i: Chromatographia. - 0009-5893. ; 42:11-12, s. 647-652
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Tidskriftsartikel (refereegranskat)abstract
- A method for determining hexahydrophthalic (HHP acid) and methylhexahydrophthalic acids (MHHP acid) from human urine was developed. These acids are metabolites of the highly sensitising hexahydrophthalic anhydride and methylhexahydrophthalic anhydride. The acids were purified from urine by liquid-solid extraction and derivatised with pentafluorobenzyl bromide to the corresponding esters. These were analysed by GC-MS in the negative-ion chemical-ionisation mode with ammonia moderating gas. Deuterium labelled HHP acid and MHHP acid were internal standards. The precision for HHP acid was 3–6% in the range 70–620 ng mL–1 and that for MHHP acid was 2–8% in the range 60–680 ng mL–1. Overall recovery of HHP acid from urine was 74–88% and that for MHHP acid 98–101%. Detection limits were 11 ng HHP acid mL–1 urine and 17 ng MHHP acid mL–1 urine. There were no significant differences between determinations of HHP acid by a previous method and the present method. Some instability of the acids in urine were found after extended storage at –20°C. The method was applicable for determination of HHP acid and MHHP acid from exposed workers.
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| 3. |
- Lindh, Christian, et al.
(författare)
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Analysis of methylhexahydrophthalic acid in human urine
- 1996
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Ingår i: Chromatographia. - 0009-5893. ; 43:11-12, s. 668-670
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Tidskriftsartikel (refereegranskat)abstract
- A method for analysis of urinary methylhexahydrophthalic acid (MHHP acid), a metabolite of the highly sensitising methylhexahydrophthalic anhydride, is described. The method is based on a double liquid-solid extraction of the MHHP acid from urine, esterification with methanol and boron trifluoride catalysis, and analysis with gas chromatography-mass spectrometry in the electron impact mode. The detection limit was 3 ng mL–1 and the precision between 2 and 5% in the range 34 to 340 ng mL–1. The method gave similar results compared to another method. Urine stored for five years at –20°C lost between 38 and 86% of the MHHP acid (range 16–85 ng mL–1).
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| 4. |
- Lindh, Christian, et al.
(författare)
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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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Ingår i: Toxicology. - 0300-483X. ; 134:2-3, s. 153-168
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Lindh, Christian, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 6. |
- Lindh, Christian, et al.
(författare)
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Determination of hexahydrophthalic acid and methylhexahydrophthalic acid in plasma after derivatisation with pentafluorobenzyl bromide using gas chromatography and mass spectrometric detection
- 1997
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Ingår i: Journal of Chromatography. B. - 1387-2273. ; 691:2, s. 331-339
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Tidskriftsartikel (refereegranskat)abstract
- A method for the simultaneous determination of hexahydrophthalic acid (HHP acid) and methylhexahydrophthalic acid (MHHP acid) in human plasma was developed. The procedure was a rapid, single step extractive derivatisation with pentafluorobenzyl bromide as the derivatisation agent. The formed pentafluorobenzyl esters were analysed by gas chromatography-mass spectrometry in negative ion chemical ionisation mode with ammonia as the moderating gas. Deuterium-labeled HHP acid and MHHP acid were used as internal standards. The detection limit was 0.4 ng/ml for HHP acid (m/z 153) and 0.3 ng/ml for MHHP acid (m/z 365). The within-day precision of the method was between 2 and 3% and the between-day precision was between 3 and 12%. The overall recovery was between 65 and 83%. A comparison between HHP acid determinations with a previous and this method showed that the methods gave similar results. The method was applicable for analysis of plasma from occupationally exposed workers.
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| 7. |
- Lindh, Christian, et al.
(författare)
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Direct measurement of hexahydrophthalic anhydride in workplace air with a transportable Fourier transform infrared spectrometer
- 1996
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Ingår i: American Industrial Hygiene Association Journal. - : Informa UK Limited. - 0002-8894. ; 57:9, s. 832-836
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Lindh, Christian, et al.
(författare)
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Human hemoglobin adducts following exposure to hexahydrophthalic anhydride and methylhexahydrophthalic anhydride
- 1998
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Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 153:2, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- Hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) are highly allergenic compounds used in the chemical industry. The aim of this study was to characterize the protein adducts in erythrocytes following exposure to HHPA and MHHPA. Blood and urine samples were obtained from 51 HHPA- and MHHPA-exposed workers. Erythrocytic proteins from HHPA- and MHHPA-exposed workers were fractionated by gel filtration and ion exchange chromatography. In vitro synthesized conjugates between tritium-labeled and unlabeled HHPA and hemoglobin (Hb) were hydrolyzed by acid or digested by Pronase E. Levels of in vivo formed anhydride-Hb adducts and urinary/plasma levels of the corresponding acids were analyzed by gas chromatography-mass spectrometry (GC-MS) and correlated. The decay of adducts was studied in workers leaving employment or during vacation. More than 85% of the adduct forming protein in vivo coeluted with Hb in gel filtration and ion exchange chromatography. At least 70% of the HHPA in the in vitro formed adducts was found on lysine by GC-MS. Similar findings were obtained using Pronase E-digested tritium-labeled Hb-HHPA. The adduct levels in workers ranged 0-26 pmol/g Hb (mean 2. 7 pmol/g Hb) for HHPA, and the range for MHHPA was 0-55 pmol/g Hb (mean 4.1 pmol/g Hb). The Spearman's rank correlation coefficient between urine data and adducts was for HHPA rs = 0.80 and for MHHPA, rs = 0.78. For the plasma, the correlation using HHPA data was rs = 0.80 and for MHHPA, rs = 0.69. The adducts seemed to be stable in vivo. The adduct levels may be used as biomarkers of exposure to HHPA and MHHPA.
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| 9. |
- Lindh, Christian
(författare)
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Metabolism and Biological Monitoring of Organic Acid Anhydrides
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to describe the metabolism and to develope methods for biological monitoring for two organic acid anhydrides (OAAs), namely hexahydrophthalic anhydride (HHPA) and methylhexa-hydrophthalic anhydride (MHHPA). The OAAs are reactive, low molecular weight chemicals used in vast quantities in the industry. Many OAAs, including HHPA and MHHPA, are potent IgE sensitisers inducing asthma, rhinitis, and conjunctivitis. Analytical methods for analyses of hexahydrophthalic acid (HHP acid) and methylhexahydrophthalic (MHHP acid; metabolites of HHPA and MHHPA) in plasma and urine and the hemoglobin (Hb) adducts of HHPA and MHHPA in erythrocytes were developed using pentaflourobenzyl bromide derivatisation and gas chromatography mass spectrometry (GC-MS). The kinetics of MHHP acid and protein adducts were investigated and the Hb adducts briefly characterised by means of gel filtration, reversed-phase liquid chromatography, and GC-MS. The levels of the acids in plasma and urine and of the Hb adducts from workers were correlated to their exposure of HHPA and MHHPA. Further, the distribution of tritium-labelled HHPA was investigated in an animals study using autoradiography and gel filtration/ scintillation. The analyses of HHP and MHHP acid in urine and plasma had high precision and accuracy. The analysis of HHPA and MHHPA adducts had a good precision. All methods had a detection limit sufficiently low for application in exposed workers. The major adduct-forming protein in human erythrocytes seemed to be Hb and the major HHPA-binding amino acid was lysine. Strong correlations were found between MHHP acid levels in plasma and urine and MHHPA in air and between levels of Hb-adducts of HHPA and MHHPA and long term or short term exposure, as determined by biomonitoring using HHP or MHHP acid in urine or plasma. Thus, the methods are applicable for biological monitoring of exposure. A fast elimination of MHHP acid in urine show that MHHP acid in plasma and urine reflect one day of exposure. The Hb adducts seemed to be stable in vivo and thus reflecting the exposure during months. In the animal study, tissue-bound HHPA/metabolites mainly occurred in the upper respiratory airways, alimentary tract, whereas no bound radioactivity was observed in the lung. A low selective binding was also observed in kidney of rats. The presented methods and results can be used for exposure assessment of OAAs and for studies of mechanisms behind allegies.
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| 10. |
- Lindh, Christian, et al.
(författare)
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Quantification method of human hemoglobin adducts from hexahydrophthalic anhydride and methylhexahydrophthalic anhydride
- 1998
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Ingår i: Journal of Chromatography. B. - 1387-2273. ; 710:1-2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- A method was developed for the determination of human hemoglobin (Hb) adducts from hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA). The procedure includes lysis of erythrocytes, dialysis of the Hb-solution followed by acid hydrolysis. The released hexahydrophthalic (HHP) acid and methylhexahydrophthalic (MHHP) acid were purified using a combined liquid-liquid and solid-phase extraction procedure followed by derivatization with pentafluorobenzyl bromide. The derivatives were analyzed using GC-MS in negative ion chemical ionization mode with ammonia as moderating gas. As internal standards, deuterium-labeled HHP and MHHP acids were used. The detection limits were 0.3 pmol/g Hb for HHP acid and 0.9 pmol/g Hb for MHHP acid. The between-day precisions for HHP acid were 18% at 2 pmol/g Hb and 10% at 13 pmol/g Hb. For MHHP acid, the precision was 27% at 2 pmol/g Hb and 14% at 22 pmol/g Hb. The method was applicable for analysis of Hb adducts from workers occupationally exposed to HHPA and MHHPA.
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