Efficacy of measures of hygiene in workers sensitised to acid anhydrides and the influence of selection bias on the results.
OBJECTIVES: Organic acid anhydrides are potential sensitisers and cause occupational airway diseases. In an intervention study the efficacy of measures of hygiene at the workplace and possible selection bias were investigated. METHODS: A first investigation with 110 workers exposed to hexahydrophthalic acid anhydride (HHPA) and methyltetrahydrophthalic acid anhydride (MTHPA) was carried out in July 1991. The results (skin prick test, specific serum IgE) showed that 20 people were sensitised, and in a challenge test the clinical relevance of the sensitisation was confirmed in six subjects. In December 1991, the hygiene conditions at the plant were improved. In November 1995 a second investigation of 84 people was performed (anamnesis, skin prick test, specific IgE, spirometry, and ambient and biological monitoring). The 27 people who had left the plant in the meantime were asked their reasons for leaving. RESULTS: The relative risk of people sensitised in 1991 of leaving the plant between 1991 and 1995 was 2.6 (95% confidence interval (95% CI) 1.4 to 4.9) compared with people without any sign of sensitisation. The percentage of people identified as sensitised in 1991, who were still working at the plant and came to the second investigation, was higher than for people without evidence of sensitisation (10/10 v 47/73; p < 0.05). In all the 10 sensitised people in 1991 the findings of the first investigation were confirmed in 1995. The rate of sensitisation in 1995 was 21%. None of the six people employed after 1991 showed evidence of sensitisation. Of the six people with clinically relevant sensitisation confirmed by a challenge test in 1991, five were still at their workplace. From 1991 they were only exposed to MTHPA at a reduced concentration (< 0.5-36 micrograms/m3 in 1995). All of them reported fewer symptoms than in 1991. No signs of bronchial obstruction were detected by spirometry at the workplace. CONCLUSIONS: In cross sectional studies there is a selection bias with a risk of underestimating the incidence of allergic diseases. The results further suggest that the improved hygiene conditions probably had a positive effect on the symptoms in sensitised people. (+info)
Determination of methyltetrahydrophthalic anhydride in air using gas chromatography with electron-capture detection.
Methyltetrahydrophthalic anhydride (MTHPA) stimulates the production of specific IgE antibodies which can cause occupational allergy even at extremely low levels of exposure (15-22 micrograms/m3). Safe use in industry demands control of the levels of exposure causing allergic diseases. Thus, the air monitoring of MTHPA is very important, and sensitive methods are required to measure low air concentrations or short-time peak exposures. This paper outlines the use of silica-gel tubes for sampling airborne MTHPA vapour, followed by analysis using gas chromatography with electron-capture detection. No breakthrough was observed at 113, 217, 673 and 830 micrograms/m3 (sampling volume 30, 60, 60 and 20 l, respectively; relative humidity 40-55%). Concentrations > 1.0 microgram/m3 could be quantified at 20-min sampling with a sampling rate of 1 l/min. The present method can also be applied to measurements of exposure to hexahydrophthalic and methylhexahydrophthalic anhydride. The risk of MTHPA exposure in two condenser plants was also assessed by determining MTHPA levels in air of the workplace. In conclusion, our method was found to be reliable and sensitive, and can be applied to the evaluation of MTHPA exposure. (+info)
Human leucocyte antigens (HLA) and trimellitic anhydride (TMA) immunological lung disease.
Occupational immunological lung disease, due to low molecular weight, reactive chemicals such as trimellitic anhydride (TMA), is an emerging health problem. If there were a marker that was highly predictive of the ability of the immune system to recognize TMA as an allergen, better prevention strategies could be employed with at risk individuals. The purpose of this study is to evaluate whether human leucocyte antigen (HLA) class specificity is associated with the development of late respiratory systemic syndrome (LRSS) or asthma due to immunological sensitivity to trimellitic anhydride (TMA). This is a case control study of 17 individuals with LRSS, 12 with asthma and 22 TMA similarly exposed individuals who did not develop LRSS or asthma. Comparing the sensitized individuals (LRSS or asthma) with the non-sensitized individuals (controls), we found no difference in frequency of any HLA antigen. In summary, the lack of association of HLA antigens with LRSS or asthma due to TMA suggests that these will not be useful markers to identify at risk individuals. (+info)
Trimellitic anhydride-induced allergic response in the guinea pig lung involves antibody-dependent and -independent complement system activation.
Trimellitic anhydride (TMA) is one of many low molecular weight compounds known to cause occupational asthma. In our previous studies the TMA-induced allergic response in guinea pigs was attenuated by depletion of complement. Specifically, the leakage of red blood cells and infiltration of inflammatory cells into the lung after TMA challenge was significantly reduced. Thus, we hypothesize that in the presence of specific antibody, TMA activates the complement system and complement activation products play a role in mediating inflammatory cell infiltration into the lung and lung hemorrhage. Guinea pigs were sensitized by intradermal injection of TMA in corn oil. An increase in the complement activation product C3a was detected in bronchoalveolar lavage, but not in plasma, of both sensitized and nonsensitized guinea pigs after intratracheal challenge with TMA conjugated to GPSA (TMA-GPSA). In vitro experiments demonstrated that TMA-GPSA caused complement activation by antibody-dependent as well as antibody-independent pathways. In sensitized animals, TMA-GPSA challenge caused significant increases in eosinophils, neutrophils, and macrophages in lung, along with increases in red blood cells and protein in the airspace. The infiltration of eosinophils was unique in that the magnitude of the GPSA/TMA-GPSA effect was significantly different between nonsensitized and sensitized animals. C3a concentrations in BAL correlated with all measures of cell infiltration in sensitized animals, but not in nonsensitized animals. These data indicate that complement activation in the absence of antibody is not sufficient for the complete allergic response to occur. Both sensitization and the complement system are required for TMA-induced eosinophilia. (+info)
Synthesis of corollosporine, an antibacterial metabolite of the marine fungus Corollospora maritima.
Corollosporine [(+/-)-3-hexyl-3,7-dihydroxy-1(3H)-isobenzofuran-1-one], an antibacterial metabolite of the marine fungus, Corollospora maritima, was synthesized by four different routes from 3-hydroxyphthalic anhydride or 2-methoxybenzoic acid as the starting material to verify its proposed structure. (+info)
Total plasma protein adducts of allergenic hexahydrophthalic and methylhexahydrophthalic anhydrides as biomarkers of long-term exposure.
OBJECTIVES: The aim of this study was to evaluate the applicability of total plasma protein adducts (TPPA) of 2 sensitizing low-molecular-weight allergens, hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA), as biomarkers of long-term exposure. METHODS: Urine samples from occupationally exposed workers were analyzed for the levels of urinary metabolites of HHPA and MHHPA, and the levels were used as the index of exposure. In addition, blood samples were obtained from the same persons, and the levels of TPPA were determined. Reversed solid phase extraction, derivatization using pentafluorobenzyl bromide, and gas chromatography-mass spectrometry analysis in the negative ion chemical ionization mode were used to quantify the exposure. To assess the suitability of TPPA as a biomarker of exposure to the anhydrides, the TPPA levels were correlated to urinary metabolite levels and hemoglobin (Hb) adducts. The toxicokinetics of TPPA were also studied to determine the elimination half-time of the adducts. RESULTS: The levels of TPPA correlated exceptionally well with the metabolite levels in the urine sampled repeatedly, giving r=0.97 for HHPA and r=0.92 for MHHPA. The TPPA of HHPA correlated highly with the Hb adducts with r=0.86. There were also good correlations between single urinary determinations and the TPPA levels (r(s)=0.71 and 0.81, respectively, for HHPA and MHHPA). The in vivo decay of TPPA gave an elimination half-time of 22 days for HHPA and 24 days for MHHPA. CONCLUSIONS: TPPA levels of HHPA and MHHPA are excellent biomarkers of long-term exposure to anhydrides. (+info)
Trimellitic anhydride-induced eosinophilia in a mouse model of occupational asthma.
Trimellitic anhydride (TMA) is a low-molecular-weight chemical known to cause occupational asthma. The present study was designed to determine if TMA elicited eosinophil infiltration into lungs of sensitized mice similar to previous studies with the protein allergen ovalbumin (OA). BALB/c mice were sensitized intradermally with 0.1 ml of 3% TMA or 0.3% OA in corn oil followed by intratracheal instillation with TMA conjugated to mouse serum albumin (TMA-MSA; 30 or 400 microg) or OA (30 microg). Nonsensitized mice received corn oil vehicle intradermally and MSA (30 microg) intratracheally. The allergic response was elicited 3 weeks later by intratracheal instillation of 30 or 400 microg TMA-MSA, OA, or control MSA. Cellular infiltration into bronchoalveolar lavage fluid (BAL) was determined 72 h later. Eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in lung homogenates was used as an estimate of numbers of eosinophils and neutrophils, respectively, in lung tissue. In TMA-sensitized mice, TMA-MSA challenge significantly increased numbers of eosinophils in BAL and EPO in lung, indicating an increase in number of eosinophils in the airway and tissue. In nonsensitized mice, TMA-MSA challenge also caused a small but significant increase in eosinophils in BAL compared to MSA control. Total IgE in both plasma and BAL was significantly higher in TMA-sensitized compared to nonsensitized mice. The eosinophil infiltration in TMA-sensitized mice was similar in magnitude to the response in OA-sensitized mice. These studies are the first to demonstrate TMA-induced eosinophilia in mouse lung and to provide a model for comparing mechanisms and mediators responsible for the substantial eosinophilia induced by TMA and OA. (+info)
Exposure to hexahydrophthalic and methylhexahydrophthalic anhydrides--dose-response for sensitization and airway effects.
OBJECTIVES: This study clarified the exposure-response relationships for the organic acid anhydrides (OAA) hexahydrophthalic (HHPA) and methylhexahydrophthalic (MHHPA) anhydrides and the development of specific immunoglobulin (IG) E and G antibodies and work-related symptoms. METHODS: In an epoxy resin-using factory, air levels of OAA were determined by gas chromatography-mass spectrometry. Occupational, smoking, and medical histories (questionnaire) were obtained for 154 exposed workers and 57 referents. Work-related symptoms of the eyes and airways were recorded, and OAA metabolites were analyzed in urine. A skin-prick test with common allergens and conjugates of OAA were performed. Specific IgE (radioallergosorbent test) and IgG (enzyme-linked immumosorbent assay) antibodies were determined in serum, and spirometry was performed. RESULTS: Air levels of the OAA were low (HHPA < 1 to 94, MHHPA < 3 to 77 microg/m3) and associated with the concentrations of the OAA metabolites in urine. Furthermore, for the exposed workers, there were high prevalences of sensitization (IgE 22%, IgG 21%), which correlated with the exposure. Neither atopy nor smoking increased this risk significantly. Furthermore, work-related symptoms were more prevalent among the exposed workers than among the referents (eyes 23% versus 14%, nose 28% versus 16%, nose bleeding 8% versus 0%, lower airways 10% versus 4%), and they were related to the exposure (adjusted prevalence odds ratios (POR) in the highest group 7.7, 3.6 and 17, respectively) and the IgE levels (POR 4.9, 3.1 and 5.6, respectively). CONCLUSIONS: In spite of the very low OAA levels in the air and metabolites in the urine, there were high and exposure-related risks of specific IgE and IgG sensitization and of work-related symptoms for the eyes, nose (especially bleeding), and lower airways. (+info)