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Biomedical subjects

L Hagmar

Publications and source records attributed to L Hagmar.

At least 109 records · Page 6Linked to original sources

B- and T-lymphocyte micronuclei in chimney sweeps with respect to genetic polymorphism for CYP1A1 and GST1 (class Mu).

Epidemiological studies have shown an increased incidence of lung cancer, bladder cancer, and esophageal cancer in chimney sweeps, probably due to their exposure to PAH in soot. The work environment for sweeps has, however, improved during the last decades. It was thus important to assess whether the present exposure still may cause genotoxic effects. A further objective was to assess whether genetic polymorphisms in metabolic enzyme activities could explain some of the variation in the parameters of genotoxicity. Venous blood samples were drawn from 71 chimney sweeps and 59 control subjects. Micronuclei were analyzed in activated peripheral B- and T-lymphocytes with preserved cytoplasm. Polymorphisms for CYP1A1 and GST1 in the sweeps were analyzed by a PCR technique. The sweeps did not have higher frequencies of micronuclei in B- or T-lymphocytes than the control subjects, when allowance was made for age and smoking in a multiple regression analysis. Further, there was no association between years of active work as a sweep and any of the two micronucleus parameters. None of the sweeps had the rare CYP1A1 genotype val/val and only one individual had the m2/m2 genotype. The presence of at least one GST1 allele (GST1+) was observed in 36 subjects (51.4%). Thirteen individuals (18.6%) were of the m1/m2 or m2/m2 genotype. And among those only seven had the combined GST1- and m1/m2 genotype. No difference was observed in B- or T-lymphocyte micronucleus frequencies between sweeps with the rare CYP1A1 genotypes m1/m2, m2/m2 or ile/val compared to individuals with the m1/m1 and ile/ile genotypes. Moreover, the GST1 deficient sweeps (GST1-) did not show any altered micronucleus frequency compared to the GST1 positive sweeps. A possible reason for the lack of genotoxic effect in sweeps is the improved hygienic conditions and change in fuels, which has decreased the exposure levels for PAH. Host polymorphisms for metabolizing enzymes did not influence the micronucleus frequencies. As the sweeps did not differ from the control subjects, with respect to micronucleus frequencies, no conclusion on the importance of host polymorphisms for genotoxic risk can be drawn.

Adult↗

Incidence of cancer and exposure to toluene diisocyanate and methylene diphenyldiisocyanate: a cohort based case-referent study in the polyurethane foam manufacturing industry.

OBJECTIVE: To assess the association between occupational exposure to toluene diisocyanate or methylene diphenyldiisocyanate and risk of cancer. DESIGN: A cohort based case-referent study. STUDY BASE: 7023 subjects employed during the period 1958 to 1987 in nine Swedish polyurethane foam manufacturing plants. MAIN OUTCOME MEASURES: Odds ratios adjusted with respect to the matching factors (age at risk, calendar year at risk, sex, and plant), calculated from the conditional logistic regression model. RESULTS: A non-significant association was found between high exposure to isocyanates and prostate cancer (OR 2.66, 90% confidence interval (90% CI) 0.39-18.1), which was not enhanced when an induction latency period of 10 years was applied. An association between isocyanate exposure and colon cancer was even weaker. No associations were seen for non-Hodgkin's lymphoma and rectal cancer. CONCLUSIONS: The tentative associations, derived from a previous cohort study, between isocyanate exposure and excess risk for non-Hodgkin's lymphoma and rectal cancer were not supported. Instead, non-significant associations with prostate cancer, and possibly colon cancer, were seen.

Case-Control Studies↗

Biological monitoring of occupational exposure to toluene diisocyanate: measurement of toluenediamine in hydrolysed urine and plasma by gas chromatography-mass spectrometry.

Exposure to toluene diisocyanate (TDI) was studied during 48 hours and biological samples from nine subjects were taken in a factory producing flexible polyurethane (PUR) foam. Five PUR workers, two white collar workers, and two volunteers were studied. The concentrations of TDI in air were determined by high performance liquid chromatography with the 9-(N-methylaminomethyl)-anthracene reagent. Urine and plasma samples were collected and the TDI related amines, 2,4-toluenediamine (2,4-TDA) and 2,6-toluenediamine (2,6-TDA), were determined (after hydrolysis) as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM) in the negative chemical ionisation mode. The concentration of TDI in air was 1%-10% of the Swedish threshold limit value (TLV) of 40 micrograms/m3. The ratio between 2,4-TDI and 2,6-TDI varied in the air samples in the range of 60%:40%-5%:95%. Calibration plots for human urine spiked with 2,6-TDA and 2,4-TDA in the range of 0.2-12 micrograms/l were produced on eight different occasions during five weeks. The SDS of the calibration plot slopes (n = 8) were less than 4%. Urine and blood samples were taken on six occasions for eight of the studied subjects and on four occasions for one subject during a two day period. The five male PUR workers showed the highest average urinary elimination rate of TDA. Two PUR workers and the two white collar workers had an elimination rate of 20-70 ng on average for the sum of 2,6-TDA and 2,4-TDA per hour and three PUR workers had an average of 100-300 ng TDA per hour. The elimination rate curves for all the studied subjects had a linear relation with exposure to TDI. The concentrations of 2,4-TDA and 2,6-TDA in plasma for the PUR factory employees were virtually stable. No relation between the elimination rates of TDA in urine and plasma concentrations of TDA was found. The five PUR workers showed plasma concentrations of the sum of 2,4-TDA and 2,6-TDA in the range 1-8 ng per ml. The two white collar workers, present only on occasions in the factory, had 0.2- ng TDA per ml plasma. The two volunteers showed an increasing concentration of TDA in plasma with time. At the end of the study their plasma concentrations were 0.6 ng/ml and 0.2 ng/ml plasma. Three subjects had the same concentration of the two TDA isomers in plasma, two subjects had about double, and two subjects had 12 times higher concentrations of 2,6-TDA than 2,4-TDA. The presented study indicates that it is possible to monitor exposure to TDI by monitoring plasma concentrations of TDA.

Adult↗

Cancer incidence and mortality in the Swedish polyurethane foam manufacturing industry.

Toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI) are used in large quantities in the polyurethane foam manufacturing industry. Both substances are mutagenic and at least TDI is carcinogenic to animals, but the occupational hazard with respect to cancer is not known. Cancer incidence and mortality patterns were therefore investigated in a cohort of 4154 workers from nine Swedish plants manufacturing polyurethane foam, employed for at least one year. Each workplace and job task in the nine plants was categorically assessed for each calendar year by an experienced occupational hygienist, for "no exposure", "low or intermittent exposure", or "apparent exposure" to TDI and MDI. The observed deficit for all cause mortality (standardised mortality ratio (SMR) 0.78, (95% confidence interval (95% CI) 0.66-0.93) became smaller (SMR 0.92) excluding the first 10 years since the start of exposure and was ascribed to a healthy worker effect. No increased risk for death from bronchial obstructive diseases was found. An almost statistically significant deficit occurred for all malignant neoplasms (standardised incidence ratio (SIR) 0.81, 95% CI 0.63-1.02); slight (not significant) increased risks were found for rectal cancer (SIR 1.66) and non-Hodgkin's lymphoma (SIR 1.53). The SIR for non-Hodgkin's lymphoma increased to 2.80 (95% CI 0.76-7.16) when the first 10 years since first exposure were excluded from the observation period. The corresponding figure for rectal cancer was 1.92 (95% CI 0.52-4.92). Further restricting the analysis to those who had experienced an apparent exposure to TDI or MDI increased the SIR for both rectal cancer (3.19, 95% CI 0.66-9.33), and non-Hodgkin's lymphoma (3.03, 95% CI 0.37-10.9). These estimates were based, however, on few incident cases. As the cohort is still young and little time has elapsed since the start of exposure, future follow ups will enable a more conclusive evaluation.

Adult↗

Mortality and incidence of cancer among sewage workers: a retrospective cohort study.

To study the incidence of and mortality from cancer among sewage workers a retrospective analysis was performed on a cohort of 656 men employed for at least one year at any one of 17 Swedish sewage plants during the years 1965-86. Assessment of exposure was done by classification of work tasks. Lower than expected total mortality (standardised mortality ratio (SMR) = 0.75, 95% confidence interval (95% CI) 0.58-0.97) and cardiovascular mortality (SMR = 0.61, 95% CI 0.39-0.91) was found. This was interpreted as a result of the healthy worker effect. For all cancers combined the mortality (SMR = 1.08, 95% CI 0.68-1.67) and morbidity (SMR = 1.02, 95% CI 0.72-1.38) were comparable with those of the general population. There were increased incidences for brain tumours (SMR = 2.19, 95% CI 0.45-6.39), gastric cancers (SMR = 2.73, 95% CI, 1.00-5.94), and renal cancers (SMR = 1.68, 95% CI = 0.35-4.90). For lung cancer the risk was reduced (SMR = 0.70, 95% CI 0.15-2.05). Allowance for a latency period of 10 years from the start of exposure did not change the pattern. Logistic modelling was used to search for exposure-response relations. In a logistic model with the confounder age forced in, renal cancer had a significant positive relation with a weighted sum of employment times, where the weights describe the classification of exposure. No exposure-response relations were found for brain tumors or gastric cancers. The increased risks are based on small numbers of cases. A future follow up will add more conclusive power to the study. Specific exposures need to be identified to allow for a better dose-response analysis.

Cause of Death↗

Increased prevalence of thyroid peroxidase antibodies (TPO-Ab) in women with glomerulonephritis.

In a cross-sectional study adjusting for age, gender, and catchment area, the prevalence of thyroid antibodies was assessed in 51 consecutive subjects with biopsy-proven glomerulonephritis and in 112 control subjects admitted for extracorporeal shock-wave lithotripsy treatment for renal stones. Women with glomerulonephritis had both a significantly greater prevalence of thyroid peroxidase antibodies (odds ratio 3.85, 95% confidence interval 1.04-14.3) and an increased prevalence of elevated serum TSH values (P = 0.007). No such difference was found in men. The prevalence of thyroglobulin antibodies did not differ between the groups. It is suggested that the possibility of an autoimmune thyroid disease should be taken into consideration in patients with glomerulonephritis, particularly in women.

Adult↗

Cancer incidence and mortality among Swedish Baltic Sea fishermen.

A 25% lower cancer mortality was found for 1360 Swedish fishermen who fished on the Baltic Sea than for the general population. The fishermen consumed twice as much fish as the population in the same county. In spite of the low overall cancer mortality, increased mortality from myeloma, as well as increased incidences of gastric carcinoma and squamous cell cancer of the skin and lips, was observed in the cohort. The decrease in risk for ischemic heart disease was not significant. Whether the dietary intake of fatty acids and selenium from fish contributed to the decreased risk was difficult to evaluate. Moreover, whether the consumption of fish from the Baltic Sea, contaminated with, for example, polychlorinated dioxins and dibenzofurans and other persistent organochlorine substances, contributed to the observed increased specific cancer risks is not known. However, the net health effect of high fish consumption from the Baltic Sea seems to be positive.

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↗

Cancer morbidity in nitrate fertilizer workers.

A cohort of 2,131 male nitrate fertilizer workers was evaluated for cancer morbidity from 1963 to 1986. No significant increase in total cancer, stomach cancer (5 actual vs 6.7 expected cases), or lung cancer (13 vs 13 expected) was found. On the other hand, 26 actual cases of prostate cancer were observed vs 16 expected cases (standardized morbidity ratio, SMR = 161; 95%, confidence interval, CI = 107-239). This risk increase however, was, not enhanced by applying at least a 10-year latency period. In a cohort of 1,148 male fertilizer workers who had never been exposed to nitrate, there was an increased incidence of lung cancer (SMR = 151,95% CI = 103-220) but not of stomach cancer or prostate cancer. There was no association between airborne nitrate exposure dose and total cancer, stomach cancer, lung cancer or prostate cancer, respectively.

Adult↗

A collaborative study of cancer incidence and mortality among vinyl chloride workers.

A large European multicentric cohort study has been coordinated by the International Agency for Research on Cancer with the objectives of investigating the dose-response relationship between liver cancer and exposure to vinyl chloride and assessing cancer risk for sites other than the liver. A nearly threefold increase in liver cancer was detected on the basis of 24 observed deaths and 8.4 expected (standardized mortality ratio 286, 95% confidence interval 186-425). The excess from liver cancer was clearly related to time since first exposure, duration of employment, and estimated ranked and quantitative exposures. Other cancer sites investigated on the basis of a priori hypotheses were either not in excess (lung) or apparently unrelated to the exposure variables (brain and lymphoma).

Adult↗

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant.

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.

Adult↗

Health effects of exposure to endotoxins and organic dust in poultry slaughter-house workers.

Twenty-three dust-exposed shacklers in the hanging departments of four poultry slaughter-house plants were examined immediately before work on a Monday morning with a standardized interview, pulmonary function tests (VC and FEV1), and blood sampling for analysis of complement factors. The examinations were repeated immediately after work the same day. Further, the individual breathing zone levels of both total dust and endotoxins were monitored during the whole work-shift. Moreover, spot samples of airborne bacteria and fungi were collected. The mean level of total dust was 6.3 mg/m3 (range 0.4-15.3 mg/m3) and of endotoxins 0.40 micrograms/m3 (range 0.02-1.50 micrograms/m3). Total levels of 4 x 10(5)-4 x 10(6) cfu/m3 of airborne bacteria, mainly coagulase-negative staphylococcal strains, but only 500-4000 cfu/m3 of fungi were found in the hanging departments. An over-shift increase in respiratory symptoms was found, but none of the workers had experienced any symptoms indicating extrinsic allergic alveolitis (EAA) or organic dust toxic syndrome (ODTS). Further, mean over-shift decreases of VC (3.1%) and FEV1 (4.1%) were found, indicating a harmful effect on the bronchi. There were, however, no associations between these over-shift decreases and the individual time-weighted average breathing zone levels of either total dust or of endotoxins. No over-shift change in serum complement factors was observed.

Abattoirs↗

An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Nordic Study Group on the Health Risk of Chromosome Damage.

To investigate whether high rates of chromosomal aberrations (CAs), sister chromatid exchange (SCE), or micronuclei(MN) in peripheral lymphocytes indicate an increased risk for subsequent cancer, a prospective cohort study of 2,969 subjects cytogenetically examined between 1970 and 1988 in four Swedish, two Finnish, and two Norwegian laboratories was initiated. To standardize for the interlaboratory variation, the results of the three cytogenetic endpoints were trichotomized for each laboratory into "low" (1st to 33rd percentile), "medium" (34th to 66th percentile), and "high" (67th to 100th percentile]. Thirty-four cancers had been diagnosed in the cohort during the observation period (1970 to 1985). The point-estimates of the standardized morbidity ratio (SMR) in the three CA strata were 90, 92, and 180, respectively. This trend for a positive association was not statistically significant (p = 0.06). There was no significant trend between SMR and the trichotomized rates of SCE. In the subcohort examined for MN only two cases of cancer had been diagnosed until now. If subjects with "high" frequencies of CA or SCE have a two-fold (or greater) risk of developing cancer as compared with individuals who have "medium" or "low" frequencies, we estimate that there is a likelihood of 80% and 70%, respectively, that this will be detectable as significant (p less than or equal to 0.05) differences after a further follow-up period of 5 years. Weaker associations between cancer risk and the cytogenetic endpoints would not be possible to evaluate until even later follow-ups.

Chromosome Aberrations↗

Comparison of the limulus amebocyte lysate test and gas chromatography-mass spectrometry for measuring lipopolysaccharides (endotoxins) in airborne dust from poultry-processing industries.

The lipopolysaccharide (endotoxin) content in airborne dust samples from three different poultry slaughterhouses was determined with both the chromogenic Limulus amebocyte lysate assay and gas chromatography-mass spectrometry analysis of lipopolysaccharide-derived 3-hydroxy fatty acids. Gram-negative cell walls were also measured by using two-dimensional gas chromatography/electron-capture analysis of diaminopimelic acid originating from the peptidoglycan. The correlation between the results of the Limulus assay and those of gas chromatography-mass spectrometry for determination of the lipopolysaccharide content in the dust samples was poor, whereas a good correlation was obtained between lipopolysaccharide and diaminopimelic acid concentrations with the gas chromatographic methods. The results suggest that it is predominantly cell-wall-dissociated lipopolysaccharides that are measured with the Limulus assay, whereas the gas chromatographic methods allow determination of total concentrations of lipopolysaccharide, including Limulus-inactive lipopolysaccharide, gram-negative cells, and cellular debris.

Air Pollutants, Occupational↗

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↗

Mortality and cancer morbidity in workers exposed to sulphur dioxide in a sulphuric acid plant.

To evaluate the risk of non-malignant respiratory disease and tumours at exposure to sulphur dioxide, a retrospective cohort study was performed on a group of 400 male workers, employed for at least six months during the period 1961-1981, in a sulphuric acid factory. Since 1969, fairly extensive measurements have been performed in the respiratory zone of the workers. The median level of total dust, over the years, was 2.2 mg/m3 (time-weighted average), of respirable dust 0.6 mg/m3, of sulphur dioxide 3.6 mg/m3, and of arsenic 11 micrograms/m3. There was a significantly increased total mortality in the period 1961-1985. Applying greater than or equal to 5 years latency period there were 47 observed deaths, giving a standardized mortality rate (SMR) of 1.57 (P = 0.002). The increased mortality was due to violence and intoxication (observed 9, SMR = 2.83; P = 0.006) and cardiovascular disease (SMR = 1.51, P = 0.05). The total tumour morbidity was not increased (observed 17, SMR = 1.17, P greater than 0.5) and there was no rise of either non-malignant or malignant lung diseases. However, there was an increase of bladder cancer (observed 5, SMR = 4.36, P = 0.006).

Chemical Industry↗