HLA and immune nonresponsiveness in workers exposed to organic acid anhydrides.
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Case-Control Studies↗
Biomedical subjects
S Skerfving
Publications and source records attributed to S Skerfving.
Measurement by ICP-MS of lead in plasma and whole blood of lead workers and controls.
OBJECTIVES: To test a simple procedure for preparing samples for measurement of lead in blood plasma (P-Pb) and whole blood (B-Pb) by inductively coupled plasma mass spectrometry (ICP-MS), to measure P-Pb and B-Pb in lead workers and controls, and to evaluate any differences in the relation between B-Pb and P-Pb between people. METHODS: P-Pb and B-Pb were measured by ICP-MS in 43 male lead smelter workers and seven controls without occupational exposure to lead. For analysis, plasma and whole blood were diluted 1 in 4 and 1 in 9, respectively, with a diluted ammonia solution containing Triton-X 100 and EDTA. The samples were handled under routine laboratory conditions, without clean room facilities. RESULTS: P-Pb was measured with good precision (CV = 5%) even at concentrations present in the controls. Freeze storage of the samples had no effect on the results. The detection limit was 0.015 microgram/l. The P-Pb was 0.15 (range 0.1-0.3) microgram/l in controls and 1.2 (0.3-3.6) micrograms/l in lead workers, although the corresponding B-Pbs were 40 (24-59) micrograms/l and 281 (60-530) micrograms/l (1 microgram Pb/I = 4.8 nmol/l). B-Pb was closely associated with P-Pb (r = 0.90). The association was evidently non-linear; the ratio B-Pb/P-Pb decreased with increasing P-Pb. CONCLUSIONS: By means of ICP-MS and a simple dilution procedure, P-Pb may be measured accurately and with good precision down to concentrations present in controls. Contamination of blood at sampling and analysis is no major problem. With increasing P-Pb, the percentage of lead in plasma increases. In studies of lead toxicity, P-Pb should be considered as a complement to current indicators of lead exposure and risk.
Adult↗
Biomarkers of exposure, antibodies, and respiratory symptoms in workers heating polyurethane glue.
OBJECTIVES: The pathogenic basis of respiratory disorders associated with isocyanates are still obscure. One reason for this is the lack of good estimates of human exposure. In this study exposure was estimated by measurement of isocyanate metabolites in biological samples. METHODS: In a factory using isocyanate based polyurethane (PUR) glue, isocyanate concentrations in air were measured by liquid chromatography. Samples from 174 employees were analysed for metabolites of 4,4'-methylene diphenyl diisocyanate (MDI) in plasma (P-MDX) and urine (U-MDX). After hydrolysis, 4,4'-methylenedianiline was measured by gas chromatography-mass spectrometry (GC-MS). The employees were screened for work related respiratory symptoms and tested for specific immunoglobulin E (IgE) and IgG antibodies directed against isocyanate conjugated to human serum albumin. RESULTS: The time weighted isocyanate concentrations in air were low (MDI < 0.2-7; hexamethylene diisocyanate (HDI) < 0.1-0.7; 2,6-toluene diisocyanate (TDI) < 0.1 microgram/m3). All subjects had detectable P-MDX and U-MDX. There were significant associations between the estimates of exposure to thermal degradation products of an MDI based glue and P-MDX (range < or = 0.10-5.5 micrograms/l); and U-MDX (< or = 0.04-5.0 micrograms/g creatinine); in cases of heavy exposure. P-MDX and U-MDX were associated with each other (r = 0.64; P = 0.0001), work related symptoms (P-MDX: P = 0.03; Mann-Whitney U test), and serum concentrations of MDI specific IgG antibodies (r = 0.26; P = 0.0007). Unexpectedly, high P-MDX and U-MDX concentrations were also encountered in workers cutting textile (P-MDX 2.4-4.5 micrograms/l; U-MDX 0.81-3.8 micrograms/g creatinine); the reason is still unknown. Equally unexpected, there were significant negative associations between P-MDX and liver function tests. CONCLUSIONS: The results clearly show the value of biomarkers for isocyanate exposure; in particular, P-MDX is useful. Further, these results show the risk connected with thermal degradation of PUR.
Adhesives↗
Structure-activity relationships of organic acid anhydrides as antigens in an animal model.
Relationships between chemical structure and immunogenicity have been studied in 13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride (cis-HHPA), trans-cyclohexane-1,2-dicarboxylic anhydride (trans-HHPA), 4-methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA3456), cis-3-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG1, and IgG2 antibodies against guinea-pig serum albumin conjugates of the anhydrides were determined by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA). Specific IgG was significantly increased in all animals, except those immunized with THPA3456 and SA, which sensitized only 3/9 and 7/9 animals, respectively. Furthermore, the specific IgG values were very low in the SA group. The titers of specific IgG1 and IgG2 were increased in the IgG-positive animals. Specific IgE was positive in all animals immunized with MA, MHHPA, MTHPA (both isomers), and MPA, and in 6/9 and 5/9 guinea pigs immunized with TMA and MMA, respectively. The IgE titers were generally very low; PCA was negative after dilutions to 1:32, or less. The results indicate a considerable variation in the sensitizing potential between different organic acid anhydrides. The most marked general effect of the chemical structure on immunogenicity was the enhancement of antibody formation when a hydrogen atom in the anhydride was substituted with a methyl group.
Anhydrides↗
Repetitive industrial work and neck and upper limb disorders in females.
A cross-sectional study was performed in which physical examinations of the neck and upper limbs were conducted on 82 currently working female industrial workers with exposure to repetitive work tasks and on 64 currently working referent subjects without exposure to repetitive work tasks. Associations between results of symptom questions and physical examination were sought with variables related to the work environment and to the individuals. In a multivariate model, there were statistically significant associations between exposure to repetitive work and diagnoses in both the neck/shoulders (prevalence odds ratio, POR = 4.6) and elbows/hands (POR = 3.5). In addition, age (POR = 1.9, 75th vs. 25th percentiles), tendencies towards subjective muscular tension (POR = 2.3), and stress/worry (POR = 1.9) were also associated with diagnoses in the neck/shoulders; however, there was not an association between these variables and the prevalence of diagnoses in elbows/hands. Standardized evaluation of videotape recordings in 74 of the industrial workers revealed significant associations between neck flexion, and elevation and abduction of the arm and the prevalence of neck/shoulder diagnoses. In the multivariate model, neck flexion was significantly associated with diagnoses in the neck/shoulders (p = 0.005). In addition, low muscle strength, lack of emotional well-being at work, and a variety of psychosomatic symptoms were associated with diagnoses in the neck/shoulders (all p < 0.001). Lack of strength was also associated with disorders of elbows/hands (p = 0.007). This study demonstrated a substantial prevalence of neck and upper limb disorders associated with repetitive work performed with a flexed neck and elevated and abducted arms, as well as a possible potentiation of these ergonomic factors by certain personal traits in some workers.
Adult↗
Cadmium in kidneys in Swedes measured in vivo using X-ray fluorescence analysis.
An X-ray fluorescence (XRF) technique using plane polarized X-rays for excitation was used for in vivo measurements of cadmium in the kidney cortex among non-occupationally exposed members of the general population in southern Sweden. The measured concentrations of cadmium in the kidney cortex of smokers (median 28 micrograms/g, n = 10) were significantly higher (P = 0.0036) as compared to those in non-smokers (median 8 micrograms/g, n = 10), and so were the cadmium concentrations in blood and urine. The results show that smoking considerably increases the cadmium concentration in the kidney cortex and that smoking is a major source of cadmium exposure in the general population of Sweden. Except in the presence of very deeply situated kidneys, where the minimum detectable concentration is high, non-invasive in vivo XRF analysis of kidney cadmium should be a useful tool for evaluating the effects of long-term low-level exposure to cadmium and the risk of kidney damage.
Adult↗
Biomonitoring of 4,4'-methylene dianiline by measurement in hydrolysed urine and plasma after epicutaneous exposure in humans.
Five healthy volunteers were dermally exposed for 1 h to 0.75-2.25 mumol 4,4'-methylene dianiline (MDA) dissolved in isopropanol, by use of a patch-test technique. Determination of MDA remaining in the patch units after exposure showed that a median of 28% (range 25-29%) was absorbed. By analysis of hydrolysed plasma, an initial accumulation of MDA could be shown, and then a decline. MDA was also detected in hydrolysed urine. The maximum rate of MDA excretion in urine was found 6-11 h after the onset of exposure. Within two subjects studied at three doses, the urinary excretion was proportional to the exposure. The elimination half-lives (elim-t1/2) in plasma and urine had medians of 13 and 7 h, respectively. In eight out of nine exposures, the elim-t1/2 was longer in plasma than in urine. Slow acetylation seemed to be associated with short elim-t1/2 in urine. The median of total MDA amount excreted in urine during 48 h, was 33 nmol for the five subjects exposed to 0.75 mumol, which corresponded to roughly 16% (range 2%-26%) of the absorbed dose while only a limited number of individuals were studied, the data still indicated that MDA in hydrolysed plasma or urine can be used for biological monitoring of occupational dermal exposure. However, the individual variation must be taken into account. Sampling should preferably be made several hours post shift. Urine is preferred before plasma at low exposures, because of its higher concentrations of MDA.
Acetylation↗
Selenoprotein P and glutathione peroxidase (EC 1.11.1.9) in plasma as indices of selenium status in relation to the intake of fish.
In Sweden fish is considered to be an important source of dietary Se. Therefore Se status was assessed in forty-one middle-aged men with widely varying fish consumption. Glutathione peroxidase (EC 1.11.1.9) and selenoprotein P in plasma were measured by radioimmunoassay. Plasma Se among the men increased slightly with increasing consumption of fish, but no such increases in the concentrations of glutathione peroxidase and selenoprotein P in plasma were observed. Moreover, no correlation was found between plasma Se and glutathione peroxidase or selenoprotein P. Instead, glutathione peroxidase was significantly correlated with selenoprotein P (r 0.73, P < 0.001), indicating that both glutathione peroxidase and selenoprotein P were functional indicators of Se status in this group. The proportion of plasma Se located in glutathione peroxidase decreased with increasing plasma Se. The results suggest that the Se consumed from fish had no apparent effect on the amount of Se incorporated into the functional selenoproteins of plasma. It is concluded that in some cases selenoproteins may be better biological markers of Se status than the total concentration of Se.
Animals↗
Mortality and cancer incidence among secondary lead smelter workers.
OBJECTIVES: To examine the mortality pattern and the cancer incidence in a cohort of long term smelter workers exposed to lead. METHODS: The cohort consists of 664 male lead battery workers, employed for at least three months in 1942-87. From 1969 the values of all blood lead samples repeatedly obtained from these workers every two to three months, have been collected in a database. The expected mortality and morbidity 1969-89 was estimated from the county rates, specified for cause, sex, five-year age groups, and calendar year. Individual exposure matrices have been calculated and used for dose-response analyses. RESULTS: The total cohort showed an increased overall mortality (standardised mortality ratio (SMR) 1.44; 95% confidence interval (95% CI) 1.16-1.79), an increased mortality from ischaemic heart diseases (SMR 1.72; 95% CI 1.20-2.42) and all malignant neoplasms (SMR 1.65; 95% CI 1.09-2.44). These risk estimates were unaffected or slightly decreased when applying a latency period of 15 years, and no dose-response pattern was shown. The non-significantly raised cancer incidence in the gastrointestinal tract (11 malignancies) in the total cohort, increased to a barely significant level in the quartile with the highest cumulative lead exposure (standardised incidence ratio (SIR) 2.34, 95% CI 1.07-4.45). No clear dose response pattern was evident when further subdividing the data into those first employed up to 1969 v those first employed after 1969 when the blood lead monitoring programme started. The risk estimate for malignancies in the gastrointestinal tract was not related to latency time. The cancer incidence was not increased at other sites. CONCLUSIONS: A slightly increased incidence of gastrointestinal cancers was found in workers exposed to lead and employed before 1970. The lead cohort also showed an increased mortality from ischaemic heart diseases. These risk estimates did not show a dose-response pattern and were not associated with latency time. The results must also be interpreted with caution because of limited numbers, and lack of dietary and smoking data.
Adult↗
Substantial decrease of blood lead in Swedish children, 1978-94, associated with petrol lead.
OBJECTIVES: To study the potential impact of environmental exposure to petrol lead, residential area, age, sex, and lead exposing hobby, on blood lead concentrations (BPb) in children. METHODS: In the south of Sweden, yearly from 1978-94, BPb was measured in 1230 boys and 1211 girls, aged between 3 and 19 (median 10; quartiles 9 and 12) years. RESULTS: For the samples of 1978, the geometric mean (GM) was 67 (range 30-250) micrograms/l in boys and 53 (18-161) micrograms/l in girls, whereas the corresponding GMs for 1994 were 27 (12-122) and 23 (12-97) micrograms/l. The sex difference was present only in children over eight. Moreover, residential area affected BPb; in particular, children living near a smelter area had raised BPbs. There was a clear ecological relation between BPb (adjusted GM) and annual lead quantity in petrol sold in Sweden, which was estimated to be 1637 tonnes in 1976 and 133 tonnes in 1993 (P < 0.001, ecological linear regression analysis, where a two year lag of petrol lead was applied). In the 171 boys and 165 girls who were sampled twice with an interval of one to four years, the decreases in BPb were estimated to be 6% (95% confidence interval 4%-8%) and 10% (8%-13%)/year, respectively. CONCLUSIONS: The present report points out the considerable beneficial effect of the gradual banning of petrol lead on the lead exposure affecting the population and differential sex specific BPb patterns due to a pronounced age effect in girls, which may be caused by older girls' lower food intake per kg of body weight, lower lung ventilation, cleaner life style, and loss of blood lead through menstrual bleedings.
Adolescent↗
Neuropathy in female dental personnel exposed to high frequency vibrations.
OBJECTIVE: To evaluate early neuropathy in dental personnel exposed to high frequency vibrations. METHODS: 30 dentists and 30 dental hygienists who used low and high speed hand pieces and ultrasonic scalers were studied, and 30 dental assistants and 30 medical nurses not exposed to vibration (all women). Vibrotactile sensibility, strength, motor performance, sensorineural symptoms and signs, and vascular symptoms in the hands, as well as mercury concentrations in biological samples and cervicobrachial symptoms, were studied. RESULTS: The two groups exposed to vibration had significant impairments of vibrotactile sensibility, strength, and motor performance, as well as more frequent sensorineural symptoms. In the dentists there were significant associations between the vibrotactile sensibility and strength, motor performance, superficial sensibility, and sensorineural symptoms. There were no associations between these findings and cervicobrachial symptoms, mercury concentrations, or smoking. There was no increase of vascular symptoms of the hands in the groups exposed to vibration. CONCLUSION: Dental hygienists and dentists had a slight neuropathy, which may be associated with their exposure to high frequency vibrations, and which may be detrimental to their work performance. Thus, development of safer equipment is urgent.
Adult↗
Effect of dietary intake of trimethylamine on human metabolism of the industrial catalyst dimethylethylamine.
OBJECTIVES: The aim was to study the effect of trimethylamine (TMA) on the metabolism of the industrial catalyst dimethylethylamine (DMEA) to ascertain whether biological monitoring of industrial exposure to DMEA is compromised and excretion of the malodorous DMEA in sweat and urine is increased by dietary intake of TMA. METHODS: DMEA (0/25 mg) and TMA (0/300/600 mg) were given simultaneously once weekly for six weeks to five healthy volunteers. Plasma was collected before and one hour after the doses, and urine 0-2, 2-4, 4-6, 6-8, and 8-24 hours after the doses. Specimens were analysed by gas chromatography with a nitrogen sensitive detector. RESULTS: Both amines were readily absorbed from the gastrointestinal tract and excreted in urine within 24 hours (DMEA 80%; TMA 86%). Oral intake of TMA increased the DMEA content of plasma and urine dose dependently, although there were large individual differences. Plasma and urinary TMA concentrations also increased, but not dose dependently. Moreover, the findings suggested the formation of endogenous TMA, little dealkylation of DMEA and TMA, and considerable first-pass metabolism. CONCLUSIONS: Although intake of TMA reduced N-oxygenation of DMEA and TMA, total urinary DMEA values (aggregate of DMEA and its oxide DMEAO excretion) were unaffected. Thus, monitoring occupational exposure to DMEA by analysis of biological specimens is not confounded by dietary intake of TMA, provided that total urinary DMEA is monitored. Although the increased urinary and hidrotic excretion of DMEA may contribute to body odour problems, they were primarily due to TMA excretion, which is much the greater.
Administration, Oral↗
Exposure to pollutants through consumption of contaminated fish.
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Animals↗
Lead intoxication caused by skeletal disease.
BACKGROUND: Inorganic lead is accumulated in the skeleton, which harbors more than 90% of the body burden of lead. If rapidly mobilized, this pool may constitute a health risk. However, clear evidence of this theory has been lacking. HISTORY: A previously healthy 36-year-old Swedish man with more than 10 years of work-related lead exposure developed headache, musculoskeletal pain, and paresthesia of both arms. Two months after the cessation of exposure, the lead level in his blood (B-Pb) was 5.5 mumol.l-1, and treatment with chelating agents was started. Shortly after the treatment period, he had an accident causing a fracture of the right collum femoris. The B-Pb was fairly stable around 1.5 mumol.l-1 for about two years after the end of exposure (95th percentile 0.6 mumol.l-1 for occupationally unexposed Swedish men). The examination showed that the patient had high skeletal turnover and clearly reduced bone density, as well as signs of tubular dysfunction. He was given the diagnosis idiopathic osteoporosis. His moderately raised bone lead concentration (about 20 micrograms.g wet weight-1; normal level in Sweden 4 micrograms.g-1) can only partly explain the raised B-Pb, remaining for years after the cessation of exposure. Instead, the main explanation is probably the increased skeletal turnover. CONCLUSIONS: A combination of a moderately increased bone lead pool and skeletal disease seems to increase the risk for lead poisoning.
Adult↗
Acid precipitation--effects on trace elements and human health.
Environmental pollution by acid precipitation increases the solubilization and mobilization of toxic metals. Through the food chain, this may alter the intake of toxic and essential elements in man. Potential adverse health effects could follow after increased human exposure. For the general population, the exposure pattern and health effects caused by aluminium, cadmium, lead and mercury are of particular concern. Although there are several indications that the exposure to toxic elements (e.g. aluminium, cadmium, lead and methylmercury), as well as the intake of essential elements (e.g. selenium), may be affected by acid precipitation, there is presently no firm evidence of adverse health effects in man. However, the present data clearly indicate that the safety margins are small. Thus, the ongoing acidification in many areas must be stopped before such effects become evident. The effects on trace element status and human health by acid precipitation were discussed at the ISTERH (International Society for Trace Element Research in Humans) Conference in Stockholm, May, 1992. The main findings are briefly summarized here.
Acid Rain↗
An assessment of neck and upper extremity disorders by questionnaire and clinical examination.
To study the usefulness of a screening questionnaire for neck/upper extremity complaints, 165 women in either repetitive industrial, or mobile and varied work, were studied by the questionnaire and by a detailed clinical physical examination. A total of 94 subjects recorded complaints in the questionnaire. In 140 subjects findings were recorded at the examination. Most subjects with findings at the clinical examination of shoulders reported complaints in the questionnaire (sensitivity 80%). For the other anatomical regions, the sensitivity was rather low (42-65%). For all regions, most subjects without findings reported no complaints (specificity 77-97%). A total of 75 subjects were given clinical diagnoses according to a set of predetermined diagnostic criteria. The capacity of the questionnaire to identify diagnoses of shoulders was higher (sensitivity 92%) than for the other regions (66-79%). Of subjects who did not qualify for diagnosis, a majority (specificity 71-81%) did not report complaints in the questionnaire. We conclude that the questionnaire approach gives a fairly good picture of the neck/upper extremity status of a working female population. However, a clear view of the size of a problem is obtained only by a detailed clinical examination, particularly as regards the neck, elbows and hands, for which the questionnaire gave an underestimate.
Adult↗
Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride.
Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems. A high fraction of HHPA-exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE-sensitized against HHPA (positive in RAST and in skin-prick test against the HHPA-HSA conjugate), and who reported work-related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work-related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE-mediated mast cell degranulation, followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.
Adult↗
Symptoms and immunologic markers induced by exposure to methyltetrahydrophthalic anhydride.
A study was performed in 43 workers exposed to methyltetrahydrophthalic anhydride (MTHPA) used as a hardener in an epoxy resin system. Ten workers sensitized to MTHPA (group SS; presence of serum IgE antibodies against a conjugate of MTHPA and human serum albumin (HSA) detected by RAST) had significantly higher levels of tryptase in nasal lavage fluid than 19 nonsensitized workers with work-related nasal symptoms (group NS) and 14 nonsensitized workers without nasal symptoms (group NN). This suggests an ongoing mast-cell-mediated reaction in the sensitized group. No statistically significant differences were found in the three groups concerning eosinophil cationic protein (ECP) and TAME-activity in lavage fluid. However, there was a significant increase in serum ECP in the SS group, as compared with a group of unexposed controls. Nasal challenge with MTHPA-HSA, performed in a subsequent study in seven workers from the SS group, six from the NS group, and seven from the NN, caused a larger increase of symptom score and a more pronounced decrease in nasal inspiratory peak flow in the SS group than in the other two groups. No significant rise was recorded for tryptase and ECP in lavage fluid in any of the three groups after challenge. The combined results of the two studies indicate that specific IgE antibodies play a pathogenetic role in at least some of the cases of work-related nasal symptoms associated with MTHPA exposure.
Blood Proteins↗