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Biomedical subjects

D Sherson

Publications and source records attributed to D Sherson.

At least 19 recordsLinked to original sources

Urinary 1-hydroxypyrene, a PAH biomarker in foundry workers.

Exposure to PAH in foundry workers has been studied by urinary 1-hydroxypyrene (HPU) levels, quantitatively measured by reversed phase HPLC. Seventy male foundry workers and 68 matched controls were investigated. Polycyclic aromatic hydrocarbon (PAH) exposure was defined by 17 breathing zone hygienic samples, consisting of 16 selected PAH compounds. Mean total PAH concentration (SD) was 10.40 (4.04) mu g/m3. A multiple regression model of tobacco consumption, age, airborne PAH-exposure and foundry work on log HPU showed a significant correlation, p < 0.001, r2 = 0.69. Only foundry work (p < 0.0001) and airborne PAH exposure (p = 0.0478) contributed significantly to the model. These data suggest that HPU is a sensitive biomarker for low-dose PAH exposure.

Adult↗

Estimation of reference values for urinary 1-hydroxypyrene and alpha-naphthol in Danish workers.

In order to assess environmentally and occupationally related exposures to PAH compounds it is essential to have reference or normal values in human body fluids. The establishment of reliable reference intervals is an absolute pre-requisite in determining relationships between internal PAH exposure in humans and health effects in occupationally exposed workers. In this context the estimation of the biological level of PAH metabolites in urine from reference populations has become increasingly important in the field of environmental and occupational toxicology. The present study describes the calculation of tentative reference values for urinary 1-hydroxypyrene on the basis of two reference populations and for urinary alpha-naphthol on the basis of one reference population in accordance with IFCC recommendations. The study subjects were 115 healthy male workers occupationally exposed to PAH at low levels and 121 reference subjects non-occupationally exposed to PAH. Tentative reference values for urinary 1-hydroxypyrene were estimated. In addition, 236 healthy male workers were used to estimate tentative reference values for urinary alpha-naphthol. The reference populations were described by distribution free one-sided tolerance intervals. The 95% one-sided tolerance limit calculated for 1-hydroxypyrene in urine was 0.053 mumol/mol creatinine for non-occupationally exposed individuals and 0.169 mumol/mol creatinine for low level PAH exposed workers, with the coverage interval (95 +/- 4.5) percent at a probability of 0.95. Thus, the probability was 0.975 that the tolerance interval included at least 90.5% of the distribution. In addition, the probability was 0.025 that the tolerance interval included > 99.5% of the population. The tolerance interval for alpha-naphthol in urine was 5.665 mumol/mol creatinine with the coverage interval (95 +/- 4.5) percent at a probability of 0.95.

Air Pollutants, Occupational↗

Correlation between work process-related exposure to polycyclic aromatic hydrocarbons and urinary levels of alpha-naphthol, beta-naphthylamine and 1-hydroxypyrene in iron foundry workers.

In two Danish iron foundries the concentration of polycyclic aromatic hydrocarbons (PAH) in 24 personal air samples of workers employed in selected processes, i.e. melters, melted iron transporters, casters, machine molders, hand molders, shake-out workers and finishing workers, were measured and correlated to levels of 1-hydroxypyrene, alpha-naphthol and beta-naphthylamine in the urine of exposed workers. The highest total airborne PAH concentrations (sum of 15 selected PAH compounds: 9.6-11.2 micrograms/m3) were associated with casting, machine molding, and shake-out. The highest concentrations of the sum of six selected airborne carcinogenic PAH compounds were found for melting, casting and machine and hand molding. As seen in other working environments involving low-level PAH exposure, the content of naphthalene was high, in general exceeding 85% of the total content of PAH compounds. The present study demonstrates that 1-hydroxypyrene is a useful and direct biomarker of low-dose occupational exposure to PAH compounds. Molding and casting had the highest pyrene levels in iron foundries. Furthermore, the data shows that levels of beta-naphthylamine in urine are significantly elevated in iron foundry workers. Hand molders, finishing workers and truck drivers tended to have the highest levels. Concerning alpha-naphthol the highest concentrations were measured in urine from casters and shake-out workers. With regard to epidemiologic studies demonstrating that molders and casters have a higher risk of lung cancer, the present study suggests that the elevated risk may be due to exposure to carcinogenic PAH compounds in iron foundries, particularly in some high-risk work processes, e.g. casting and molding. In addition, the present study suggests that biological monitoring of 1-hydroxypyrene and beta-naphthylamine may be used to estimate the individual exposure, which seems to be correlated with exposure during individual work processes.

2-Naphthylamine↗

Exposure of iron foundry workers to polycyclic aromatic hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as biomarkers for exposure.

Exposure to polycyclic aromatic hydrocarbons (PAHs) in foundry workers has been evaluated by determination of benzo(a)pyrene-serum albumin adducts and urinary 1-hydroxypyrene. Benzo(a)pyrene binding to albumin and 1-hydroxypyrene were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and reverse phase high performance liquid chromatography (HPLC), respectively. 70 male foundry workers and 68 matched controls were investigated. High and low exposure groups were defined from breathing zone hygienic samples, consisting of 16 PAH compounds in particulate and gaseous phase. Mean total PAH was 10.40 micrograms/m3 in the breathing zone, and mean dust adsorbed PAH was 0.15 microgram/m. All carcinogenic PAH was adsorbed to dust. Median benzo(a)pyrene-albumin adduct concentrations (10-90% percentiles) were similar in foundry workers (smokers 0.55 (0.27-1.00) and non-smokers 0.58 (0.17-1.15)) pmol/mg albumin and age matched controls (smokers 0.57 (0.16-1.45) and non-smokers 0.70 (0.19-1.55) pmol/mg albumin). Median 1-hydroxypyrene concentrations were significantly higher (P < 0.0001) in smoking and non-smoking foundry workers (0.022 (0.006-0.075) and 0.027 (0.006-0.164)) mumol/mol creatinine than in smoking and non-smoking controls (0 (0-0.022) and 0 (0-0.010) mumol/mol creatinine). Dose-response relations between total PAH, pyrene, carcinogenic PAHs, and 1-hydroxypyrene for smokers, and polycyclic aromatic hydrocarbons adsorbed to dust for non-smokers are suggested. Exposure to PAHs adsorbed to dust showed an additive effect. There was no correlation between the concentrations of 1-hydroxypyrene and benzo(a)pyrene-albumin adducts. The change in 1-hydroxypyrene over a weekend was also studied. Friday morning median 1-hydroxypyrene concentrations were significantly higher in both smokers and non-smokers (0.021 (0-0.075) and 0.027 (0.06-0.164)) mumol/mol creatinine than Monday morning median concentrations (0.007 (0-0.021) and 0.008 (0-0.021) mumol/mol creatinine). Smoking did not affect the concentrations of 1-hydroxypyrene or benzo(a)pyrene-albumin adducts. These data suggest that 1-hydroxypyrene is a sensitive biomarker for low dose PAH exposure. Exposure to PAHs may be aetiologically related to increased risk of lung cancer in foundry workers.

Adult↗

Superoxide anion release from blood monocytes and alveolar macrophages in patients with diffuse lung fibrosis.

Superoxide anion release (O2-) after stimulation with phorbol myristate acetate was measured in alveolar macrophages (AM) obtained by bronchoalveolar lavage and in blood monocytes from 47 patients with diffuse interstitial lung disease: idiopathic pulmonary fibrosis (N = 15), hypersensitivity pneumonitis (N = 7), pneumoconiosis (N = 6) and sarcoidosis (N = 19). Differential cell counts demonstrated a lymphocyte predominance in patients with hypersensitivity pneumonitis (HP) and sarcoidosis while the other groups had neutrophil predominance. No correlation between O2- activity in alveolar macrophages (AM) or blood monocytes (BM) compared to lung function (VC and diffusing capacity) could be demonstrated. Smoking pneumoconiotics had significantly decreased BM O2- release (1.25 +/- 0.25 (SEM) nmol/min/10(6) cells) and significantly increased AM/BM O2- ratios (2.04 +/- 0.26) compared to smokers with idiopathic pulmonary fibrosis (IPF) who had the following mean values: BM O2- release = 2.58 +/- 0.25 and AM/BM O2- ratio = 0.86 +/- 0.23. When matched for sex and smoking, a significantly increased AM/BM O2- ratio was seen among patients with HP (2.19 +/- 0.98) in comparison with patients who had sarcoidosis (0.40 +/- 0.18). Patients with either HP or pneumoconiosis had generally elevated AM O2- release and reduced BM O2- release. These results suggest that environmentally related interstitial lung disorders (HP and pneumoconiosis) may be associated with elevated AM O2- release relative to BM O2- release in comparison to non-environmentally related disorders (IPF or sarcoidosis).

Adult↗

Interaction of smoking, uptake of polycyclic aromatic hydrocarbons, and cytochrome P450IA2 activity among foundry workers.

An increased lung cancer risk has been described among foundry workers. Polycyclic aromatic hydrocarbons (PAHs) and silica are possible aetiological factors. This study describes a urinary PAH metabolite, 1-hydroxypyrene (hpU), as well as the degree of cytochrome P450IA2 activity/induction as reflected by the urinary caffeine ratio (IA2) in 45 foundry workers and 52 controls; IA2 was defined as the ratio of paraxanthine 7-demethylation products to a paraxanthine 8-hydroxylation product (1,7-dimethyluric acid). Mean exposure concentrations for foundry workers were defined by breathing zone hygienic samples (respirable dust 1.2 to 3.52 mg/m3 (93 samples)) and as total PAH (0.46 micrograms/m3) and pyrene concentrations (0.28 micrograms/m3) (six samples). Non-smoking controls and foundry workers had similar IA2 ratios (5.63, 95% confidence interval (95% CI) 4.56-6.70 and 4.40, 95% CI 3.56-5.24). The same was true for smoking controls and foundry workers (9.10, 95% CI 8.00-10.20 and 8.69, 95% CI 7.37-10.01). Both smoking groups had raised IA2 ratios compared with non-smokers (p less than 0.01). Non-smoking controls and foundry workers had similar hpU concentrations (0.16, 95% CI 0.10-0.22 and 0.11, 95% CI 0.09-0.13 mumol/mol creatinine). Smoking foundry workers had raised hpU concentrations (0.42, 95% CI 0.25-0.59) compared with smoking controls (0.26, 95% CI 0.18-0.34) (p less than 0.01). A small subgroup of smoking foundry workers with the highest exposures to both silica and PAH also had the highest hpU concentrations (0.70, 95% CI - 0.07-1.47 mumol/mol creatinine) (p less than 0.04). Increased hpU concentrations in smoking foundry workers suggest a more than additive effect from smoking and foundry exposures resulting in increased PAH uptake. Increased P450IA2 enzyme activity was only found in smokers and no additional effect of foundry exposures was seen. These data suggest that smoking as well as work related PAH exposure may be casually related to increased risk of lung cancer in foundry workers.

Adult↗

Comparison of alveolar macrophage and blood monocyte oxidative burst response in pulmonary sarcoidosis.

The alveolitis of sarcoidosis is dominated by lymphocytes and mononuclear phagocytes and chronic macrophage activation may play a role in the pulmonary interstitial fibrosis of sarcoidosis. We measured superoxide anion release of alveolar macrophages from sarcoidosis patients after in vitro stimulation, as toxic oxygen radicals have been proposed as mediators of chronic tissue damage. In untreated patients alveolar macrophage activity was normal, but significantly lower than in blood monocytes. However, a negative correlation between lymphocytosis in bronchoalveolar lavage fluid and macrophage oxidative metabolism was observed, showing that only patients with high intensity alveolitis have a decreased oxidative burst response after in vitro stimulation. This may reflect in vivo activation of the cells with subsequent reduced ability to respond after additional stimulation in vitro. Patients with radiological stage I had lower alveolar macrophage response than patients in stage II or III. There was no correlation with SACE levels, lung function tests or smoking habits. Nine patients were reinvestigated after treatment with prednisolone. Although the lymphocytosis of lavage fluid was only insignificantly changed, all but one patient showed improved macrophage release of superoxide anion. Blood monocyte oxidative burst response was normal in all patients before and after treatment. In conclusion, only mononuclear phagocytes of the target organ (lung) showed an altered function and the most pronounced decrease was observed in sarcoid patients with active alveolitis. Chronic low grade toxic oxygen radical release of alveolar macrophages may be involved in the pathology of pulmonary sarcoidosis.

Adult↗

Biological monitoring of foundry workers exposed to polycyclic aromatic hydrocarbons.

This investigation describes benzo(a)pyrene (BP) serum protein adduct concentrations in 45 foundry workers and 45 matched non-occupationally exposed controls. High and low BP exposure groups were defined using breathing zone hygienic samples for both quartz and BP exposures. A newly developed enzyme linked immunosorbent assay detected benzo(a)pyrenediolepoxide-I binding to serum protein. Mean BP protein adduct concentrations (SD) for non-smoking (24.0 BP equivalents/100 micrograms protein (21.0] and smoking (28.0 (18.2] foundry workers were significantly higher than mean values for non-smoking (7.23 (8.72] and smoking (14.2 (24.4] controls. Foundry workers with high exposures to either quartz (28.4 (15.5] or BP (30.7 (19.3] had slightly raised mean adduct concentrations compared with foundry workers with low exposure for quartz (23.9 (23.1] or BP (24.5 (19.4). Highest mean adduct concentrations were found among a small group of workers with simultaneous high exposures to both quartz and BP (39.2 (6.5] suggesting an additive effect. These data support the ideas of a possible aetiological connection between an increased risk of lung cancer and BP exposure among foundry workers, and an additive effect between BP and quartz. Measurement of BP serum protein adduct concentrations appears to be a useful method by which groups exposed to BP may be biologically monitored.

Adult↗

A dental technician with pulmonary fibrosis: a case of chromium-cobalt alloy pneumoconiosis?

A 45 yr old male developed pulmonary fibrosis after 29 yrs of employment as a dental technician. He subsequently developed adenocarcinoma of the lung. Diffuse interstitial fibrosis was seen using light microscopy. Neutron activation analysis of non-neoplastic lung tissue demonstrated high levels of chromium and cobalt suggesting the possibility of a chromium-cobalt alloy pneumoconiosis.

Biopsy↗

Morbidity of pulmonary tuberculosis among silicotic and nonsilicotic foundry workers in Denmark.

Increased tuberculosis risk associated with silicosis is well described. The present study defines the incidence of pulmonary tuberculosis among 5424 nonsilicotic and 155 silicotic male foundry workers observed between 1967 and 1986. For the 18-year follow-up period, the following groups had statistically significant increased standard incidence rates (SIR) for pulmonary tuberculosis: silicotics, SIR = 1000 (95% CI = 272 to 2561, P less than .01); nonsilicotics employed at least 25 years, SIR = 353 (95% CI = 130 to 768, P less than .01); and for the entire cohort, SIR = 201 (95% CI = 125 to 397, P = .01). These results suggest that silica exposure may cause an increased pulmonary tuberculosis risk among nonsilicotic foundry workers.

Cohort Studies↗

Occupationally related respiratory symptoms in trout-processing workers.

All eight production workers from a small trout-processing factory were studied because of respiratory or rhinitis symptoms when working next to the automatic gutting machine. Seven of the eight had positive histamine provocation tests. Four patients had elevated total IgE levels while one had a slightly elevated eosinophil count. All workers had either weakly or moderately positive RAST against contaminated water from the outlet drain of the gutting machine. This water contained 1 microgram endotoxin/ml. We concluded that five of the workers had probably developed occupationally related asthma from inhalation of contaminated aerosol from the gutting machine. Inhalation of endotoxin from gram-negative bacteria may be the cause of this disorder. An alternative explanation is a Type I allergy caused by fish or bacterial protein with or without a simultaneous effect of endotoxin.

Adult↗

Small opacities among dental laboratory technicians in Copenhagen.

After a case of advanced pneumoconiosis occurred in a dental laboratory technician, 31 other dental technicians and 30 control subjects controlled for smoking habits, sex, and age were investigated. More technicians (55%) than controls (30%) had at least grade 1 dyspnoea (p greater than 0.05). Multiple regression analysis showed that 13 technicians who had produced dental prostheses for at least 15 years had consistently lower lung function (FVC, FEV1, FEV1/FVC, MEF50, and DCO single breath), although the differences were not statistically significant. All mean lung function values for technicians and controls were within normal limits. Increases in MEF50 after breathing 80% helium and 20% O2 failed to show small airways dysfunction among the technicians. Of the six with radiological pneumoconiosis (5 simple, 1 advanced) four had symptoms. All three biopsy specimens showed varying degrees of pulmonary fibrosis. DCO single breath was diminished in four of the six. One male dental technician had scleroderma and possibly Erasmus syndrome. Blind readings showed an increased number of suspicious chest x rays films (greater than or equal to category 0/1) among older smokers and ex-smokers (p = 0.013) regardless of occupation. Our results support other evidence that dental technicians are at risk of developing pneumoconiosis. Therefore, adequate hygienic control of dental laboratories is indicated.

Adolescent↗