Search PubMedSearch

Biomedical subjects

H Welinder

Publications and source records attributed to H Welinder.

At least 19 recordsLinked to original sources

Methyltetrahydrophthalic anhydride in air--sampling and analysis.

Methyltetrahydrophthalic anhydride (MTHPA), an organic anhydride, is a sensitizing agent even at low air concentrations: no methods for its sampling and analysis have previously been reported. This paper outlines the use of Amberlite XAD-2 for sampling MTHPA vapour in air, followed by analysis using gas chromatography with flame ionization detection. The level of detection corresponds to a concentration in air of 10 micrograms m-3 for a 20 l. sampling volume. Up to 200 l. air has been sampled, at a sampling rate of 1 l. min-1, without detectable losses. The adsorption efficiency and the stability of the anhydride in the XAD-2 tubes were not influenced by a relative air humidity (RH) of 40%, but at RH 80% there was a loss of 18% at 50 l. air-sample volume. Results from sampling in XAD-2 tubes were 8% lower than those from parallel sampling in midget bubblers containing 10 ml 0.01 M sodium hydroxide.

Air Pollutants, Occupational

Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers.

One hundred and forty four current and 26 former workers in a plant producing barrels for rocket guns from an epoxy resin containing methyltetrahydrophthalic anhydride (MTHPA; time weighted average air concentration up to 150 micrograms/m3) were studied. They showed higher frequencies of work related symptoms from the eyes (31 v 0%; p < 0.001), nose (53 v 9%; p < 0.001), pharynx (26 v 6%; p < 0.01), and asthma (11 v 0%; p < 0.05) than 33 controls. Also they had higher rates of positive skin prick test to a conjugate of MTHPA and human serum albumin (16 v 0%; p < 0.01), and more had specific IgE and IgG serum antibodies (18 v 0%; p < 0.01 and 12 v 0%; p < 0.05 respectively). There were statistically significant exposure-response relations between exposure and symptoms from eyes and upper airways, dry cough, positive skin prick test, and specific IgE and IgG antibodies. There was a non-significant difference in reaction to metacholine between exposed workers and non-smoking controls. In workers with and without specific IgE antibodies, differences existed in frequency of nasal secretion (54 v 23%; p < 0.05) and dry cough (38 v 12%; p < 0.05). Workers with specific IgG had more dry cough (38 v 12%; p < 0.05), but less symptoms of non-specific bronchial hyperreactivity (0 v 26%; p < 0.05). Atopic workers sneezed more than non-atopic workers (65 v 30%; p < 0.01). In a prospective study five sensitised workers who left the factory became less reactive to metacholine, and became symptom free. In 41 workers who stayed, there was no improvement, despite a 10-fold reduction in exposure. The results show the extreme sensitising properties of MTHPA.

Adolescent

Determination of hexahydrophthalic anhydride in air using gas chromatography.

Two methods for the determination of hexahydrophthalic anhydride (HHPA) in air were developed. In a solid sorbent method, HHPA was sampled in Amberlite XAD-2 tubes, eluted in toluene and analysed by gas chromatography with flame ionization detection. The sampling rates were 0.2 and 1.0 l/min. At 15 micrograms/m3 (relative humidity less than 2%) and 27 micrograms/m3 (relative humidity 70%) no breakthrough was observed. However, at 160 micrograms/m3 (relative humidity less than 2%), 6% breakthrough was found. The sampling efficiency of the sampling rates 0.2 and 1.0 l/min did not differ. In a bubbler method, HHPA was sampled in bubblers filled with 0.1 M sodium hydroxide solution. The sodium salt of hexahydrophthalic acid was formed. No breakthrough was observed using a sampling rate of 1.0 l/min. The samples were stable during storage for eight weeks in a refrigerator. The HHP acid was esterified with methanol-boron trifluoride and analysed by gas chromatography-flame ionization detection. Apparatus for the generation of standard atmospheres of HHPA, in the range of 10-3000 micrograms/m3, was developed using the diffusion principle. For the solid sorbent method the precision (coefficient of variation) of the overall method was 2-7%, and for the bubbler method 3-19% (range 15-160 micrograms HHPA/m3; relative humidity = less than 2-70%). A comparison between the two methods was performed using the standard atmosphere. The concentrations found by the solid sorbent method were 86-98% of those found by the bubbler method (range 15-160 micrograms HHPA per m3; relative humidity = less than 2-70%). In work environment air, 93% was found using the solid sorbent method relative to the bubbler method at a mean concentration of 330 micrograms/m3 (coefficient of variation = 39%; range 200-540 micrograms/m3). For both methods, concentrations greater than 3 micrograms/m3 could be quantified at 60 min sampling with a sampling rate of 1.0 l/min.

Air Pollutants, Occupational

Serum IgE and lung function in workers exposed to phthalic anhydride.

A total of 23 phthalic anhydride (PA)-exposed workers (air levels up to 17 mg/m3) showed significantly (P less than 0.01) more workrelated symptoms in their eyes (48% vs 6%) and nose (39% vs 0) than did 18 unexposed control subjects. Two of the exposed workers had PA-associated asthma. Surprisingly, the control group exhibited significantly (P less than 0.05) more symptoms of nonspecific bronchial hyperreactivity (44% vs 13%). The exposed workers showed significantly higher levels of total serum IgE (medians, 32 vs 15 kIU/l, P less than 0.05), although values for specific IgE against PA did not differ. This may indicate that such exposure can facilitate the entry of common allergens. There was a significant difference in PA-specific IgG [enzyme-linked immunosorbent assay (ELISA) ratios 0.21 vs 0.12; P less than 0.01]. There were no differences in lung function with regard to vital capacity (VC) and forced expiratory volume (FEV1), closing volume expressed as a percentage of VC (CV%), volume of trapped gas (VTG) before and after inhalation of metacholine, or carbon monoxide transfer factor (TLCO), whereas exposed workers displayed significantly higher late expiratory flow rates (MEF50 and MEF25). In a [99mTc]-diethylenetriamine penta-acetate (DTPA) clearance test, there was no difference between exposed subjects and controls. In summary, exposure to PA did not cause subclinical effects of the lungs. Subjects with lower-airway symptoms showed lower FEV1, MEF50, and MEF25 values and higher VTG (after metacholine) than did those without symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

An epidemiological study of cancer risk among workers exposed to ethylene oxide using hemoglobin adducts to validate environmental exposure assessments.

Cancer morbidity was investigated in a cohort of 2,170 ethylene oxide (EO)-exposed workers from 2 plants producing disposable medical equipment. The subjects had been employed for at least 1 year during the periods 1970-1985 and 1964-1985, respectively. The exposure to EO was assessed for each of six job categories in the plants with respect to each calendar year, on which basis values for individual cumulative exposure to EO (ppm-years) were calculated. The levels of hydroxyethyl adducts to N-terminal valine (HOEtVal) in hemoglobin fitted well with the values estimated for airborne exposure to EO. No increased cancer incidence was found [standardized morbidity ratio (SMR), 0.78; 95% CI, 0.49-1.21)]. No leukemia was observed, but one case of non-Hodgkin's lymphoma, one case of myeloma, and one case of polycythemia vera were diagnosed as compared with two expected hematopoietic and lymphatic tumors (SMR, 1.54; 95% CI, 0.32-4.5). No stomach cancer was detected as compared with the 0.5 case expected. There were no significant exposure-response associations between estimates of exposure to EO and cancer morbidity.

Adult

Hexahydrophthalic acid in urine as an index of exposure to hexahydrophthalic anhydride.

Post-shift and next-morning urine was sampled from workers exposed to hexahydrophtalic anhydride (HHPA), an epoxy hardener, sensitising at low exposure levels. Exposure levels of HHPA in air (gas chromatography, GC) in the range of 30-270 micrograms/m3 corresponded to urinary concentrations of 0.9-2.8 mumol hexahydrophthalic acid (HHP acid; GC-mass spectrometry)/mmol creatinine. In the morning samples the concentrations were less than 0.04-0.3 mumol HHP acid/mmol creatinine. In unexposed controls, the level was less than 0.1 mumol/mmol creatinine. A correlation was found between the time-weighted levels of HHPA in air and HHP acid in the post-shift urine (rs = 0.93; P less than 0.023), indicating that the determination of HHP acid in urine is suitable for biologic monitoring of HHPA exposure.

Adult

Immunologic tests of specific antibodies to organic acid anhydrides.

The outcome of immunologic tests of antibodies directed against hapten conjugates of organic acid anhydrides and human serum albumin (HSA) has been studied in workers exposed to phthalic anhydride (PA), methyltetrahydrophthalic anhydride (MTHPA), hexahydrophthalic anhydride (HHPA), and methylhexahydrophthalic anhydride (MHHPA). HSA conjugates of PA, MTHPA, HHPA, MHHPA, and maleic anhydride (MA) have been prepared and used in the tests. The hapten densities (HD) of the conjugates were varied by different molar ratios of hapten and macromolecule in the preparative procedure. Skin prick reactions to MTHPA-HSA increased with rising HD over the range 6-13 mol/mol. The achieved HD was tested by spectrometric and gas chromatographic methods. In RAST of IgE antibodies MTHPA-HSA with HD six and 25 showed significantly lower bindings than conjugates with intermediate HD. There was a good correlation between skin prick tests and RAST. Of 234 workers tested [MTHPA (n = 145), and HHPA (n = 89)], 45 had a skin prick reaction greater than or equal to 50% of the histamine reaction (1 mg/ml). All but two of these were RAST positive (RAST value greater than 0.3%; 0.3% upper range in 147 controls; MTHPA, n = 63; HHPA, n = 84). Nine RAST positive workers had no obvious skin prick reaction. However, their RAST values were low (less than 0.8%). In exposed workers, the ELISA value of specific IgG antibodies to MTHPA-HSA showed optimal values when tested with the HD 13 conjugate.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay

Specific antibodies to methyltetrahydrophthalic anhydride in exposed workers.

A group of 145 workers exposed to methyltetrahydrophthalic anhydride (MTHPA) was investigated. They were working in a plant which, since 1983, handled an epoxy resin with MTHPA as a hardener. Specific IgE antibodies (RAST) to a conjugate between MTHPA and human serum albumin (HSA) were statistically significantly increased (P = 0.001; 26 subjects = 18% positive) in the exposed group, compared to a non-exposed control group (n = 33). One positive worker was only exposed for 2 months. Twenty-three exposed subjects were also skin-prick test positive to MTHPA-HSA. The exposed group was divided into three different exposure categories, according to their contact with the epoxy resin. The average exposure levels at the time of the investigation were, in zone I 0.085 mg/m3, in zone II 0.014 mg/m3, and in zone III 0.010 mg/m3, though the exposure probably had been higher earlier. There was an association between exposure intensity and RAST-positive persons (P = 0.0025, chi-square trend test). Forty-four persons (30%) were smokers, and 16 (11%) atopics. No association between sensitization and either atopy or smoking was found. There was an association between exposure intensity and specific IgG antibodies (P = 0.0003, chi-square trend test). Specific IgG4 antibodies were closely related to specific total IgG antibodies (P = 0.0001). These findings demonstrate that MTHPA is a sensitizing agent at low levels of exposure.

Antibody Specificity

Mortality and cancer morbidity in cohorts of asbestos cement workers and referents.

Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure).

Asbestos

Small airways function in workers processing polyvinylchloride.

In a polyvinyl chloride (PVC) processing plant, 20 workers employed as machine attendants and calender operators, and thus exposed to PVC thermal degradation products (PTDP) and phthalic acid esters (PAE; up to 2 mg/m3), were studied. The control group was 19 unexposed workers. The exposed subjects had more symptoms from eyes and upper airways than the controls, probably mainly associated with PTDP. Two (10%) exposed workers had mild work-related asthma vs no control; five (25%) vs one (5%) symptoms of unspecific bronchial hyperreactivity. One exposed subject had a significantly raised level of IgG against phthalic anhydride, indicating that sensitization can occur in PVC processing. No significant differences were found between exposed and control subjects with regard to spirometry (VC, FEV1, FEF50, FEF75) or volume of trapped gas (VTG, an indicator of small airways disease) before or after metacholine inhalation. Thus, we could not find effects of PTDP or PAE on the small airways.

Adult

Allergic airway disease caused by methyl tetrahydrophthalic anhydride in epoxy resin.

Work-associated rhinitis and asthma occurred in a subject exposed to methyl tetrahydrophthalic anhydride (MTHPA) used as a curing agent in an epoxy resin system. He displayed bronchial hyperreactivity in provocation with methacholine, as well as skin prick test positivity and specific immunoglobulin E (IgE) serum antibodies, against a conjugate of MTHPA and human serum albumin. Thus, it seems likely that the disease was caused by an IgE-mediated allergy.

Adult

Cytogenetic and hematological effects in plastics workers exposed to styrene.

For 20 glass-reinforced plastics workers exposed to styrene and 22 unexposed referents, the frequency and size distribution of micronuclei were determined for lymphocytes stimulated with phytohemagglutinin or pokeweed mitogen, and white blood cell counts were made. Furthermore, chromosome aberrations were scored for 11 of the exposed subjects and 15 of the referents. The mean level of styrene in the breathing zone of the workers was 56 mg/m3. Workers exposed to styrene did not show an increase in any of the cytogenetic end points studied when the effect of age and smoking was allowed for in a multiple regression analysis. A significant 30% increase in the number of peripheral monocytes was observed for the exposed workers. No correlations between the cytogenetic and hematological tests on one hand and the length of exposure time on the other could be detected.

Adolescent

Railroad workers with pleural plaques: I. Spirometric and nitrogen washout investigation on smoking and nonsmoking asbestos-exposed workers.

Eighty-seven workers exposed to asbestos in a railroad car repair shop, with characteristic asbestos-induced pleural plaques, underwent extensive lung-function examination. Vital capacity (VC) showed the greatest reduction among the static lung volumes, with an asymmetrical distribution of one-fourth of the subjects below 80% of the predicted value. Logistic regression demonstrated VC to be sufficient for optimal discrimination of asbestos-exposed subjects from a group of matched controls. No further discriminatory power was gained by additional spirometric measures, lung mechanics, blood gas analysis, or diffusing capacity. Smoking had an influence on dynamic but not on static lung volumes. In conclusion, reduced static lung volumes among smoking asbestos-exposed workers with pleural plaques should, in the absence of other lung diseases, be mainly attributed to the asbestos exposure.

Adult

Railroad workers with pleural plaques: II. Small airway dysfunction among asbestos-exposed workers.

Increased volume of trapped gas (VTG) was found in 87 asbestos-exposed railroad repair shop workers, divided into three subgroups according to smoking habits. All the examined subjects had pleural plaques. Determination of VTG was used to study function of small airways. Increased VTG was found among asbestos-exposed smokers as well as nonsmokers. In both groups the VTG:TLC ratio was elevated compared with controls. Increased VTG is a sign of small airways dysfunction. In asbestos-exposed subjects, it might be caused by an early peribronchial reaction to inhaled asbestos fibers.

Adult

Comparison among five mutagenicity assays in workers producing polyurethane foams.

Thirty-two male individuals exposed to isocyanates and amines during the production of plastic foams and 20 male referents were studied by cytogenetic methods (chromosomal aberrations, sister chromatid exchanges and micronuclei in lymphocytes) and by urinary mutagenic assays (thioether concentrations and mutagenic activity with Salmonella TA98 and E. Coli WP2 uvrA). The occupational exposure was monitored by measurements of toluene diisocyanate and N-methylmorpholine in work-room air. The levels were below the current Swedish hygienic standards. Although all parameters, except the sister chromatid exchanges, showed increased mean values for the exposed group compared to the referents, only the urinary thioether concentrations differed significantly. The study was, however, non-conclusive with regard to a genetic effect of the occupational exposure as measured by the cytogenetic parameters. This may be due to the low exposure level. In the micronuclei frequencies there was a significant effect of age. Smoking significantly affected the SCE frequencies, the thioether concentrations and the mutagenic activities in the Salmonella assay. There were statistically significant correlations between the urine specimens collected during one working day and the following morning with regard to the mutagenic activities in the Salmonella and E. coli assays, and in the thioether concentrations as well. The association between the different cytogenetic and urinary mutagenic assays were weak but there were several statistically significant correlation coefficients, indicating that the variables may have a common metabolic background.

Adult

Specific serum antibodies against phthalic anhydride in occupationally exposed subjects.

In two plants producing alkyde and unsaturated polyester resins, the time-weighted average air level during loading of phthalic anhydride (PA) was 6.6 (1.5 to 17.4) mg/m3. In a full workday the level was 0.4 mg/m3. In 60 workers, symptoms of rhinitis and/or conjunctivitis were frequently reported, mostly by heavily exposed workers (69%). Five workers (14%) with PA-associated asthma were found. All were heavily exposed during some period. There was no difference between the exposure groups with regard to total serum level of IgE, IgG, and IgM, nor specific IgE and IgM against PA. There was a significant difference of specific IgG against PA between heavy and low exposure groups (p = 0.01). One worker with asthma had an increased specific IgE level. Subjects with symptoms did not differ from subjects without symptoms in total serum IgE, IgM, IgA, or specific IgE and IgM. However, subjects with rhinoconjunctivitis had lower total IgG than the other workers (p = 0.01). The subjects with asthma had significantly higher values for specific IgG than the asymptomatic subjects (p = 0.005). Four subjects had specific IgG antibodies of subclass 4 (IgG4). Three of these four subjects had asthma, and one had rhinitis. These findings demonstrate that specific IgG is an index of PA exposure and support the hypothesis that specific IgG4 under some circumstances, may be a pathogenetic factor in asthma.

Antibodies

IgG antibodies against polyisocyanates in car painters.

A group of thirty car painters exposed to vapours and aerosols of paint containing prepolymer andmonomer of hexametylene diisocyanate (HDI) was investigated. Specific antibodies against monomer HDI and prepolymerized HDI were analysed with RAST (IgE) and ELISA (IgG) assays after conjugation of the haptens with human serum albumin. There was no significant increase of serum IgG antibodies against HDI monomer, nor of specific IgE antibodies against HDI monomer or prepolymer. Specific IgG antibodies against prepolymerized HDI were significantly increased, as compared with non-exposed referents (medians 0.11 vs 0.03 absorbance (A]. Six car painters were found to have specific IgG antibodies of subclass 4 against HDI prepolymer, four also against HDI monomer. This shows an association between exposure and specific IgG antibodies. Thirteen subjects had suffered symptoms of rhinitis and/or conjunctivitis, and ten had symptoms from the bronchi (two asthma). There was no significant association between symptoms and levels of specific antibodies. Most of the symptoms were slight and unspecific, probably due to irritative effects of the exposure.

Adult