Non-Hodgkin lymphoma and occupational exposures: multiple exposures not = multiple papers.
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Biomedical subjects
Publications and source records attributed to R Vermeulen.
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AIMS: To study the validity of using a cross-sectional industry-wide exposure survey to develop exposure groupings for epidemiological purposes that extend beyond the time period in which the exposure data were collected. METHODS: Exposure determinants were used to group workers into high, medium, and low exposure groups. The contrast of this grouping and other commonly used grouping schemes based on plant and department within this exposure survey and a previously conducted survey within the same industry (and factories) were estimated and compared. RESULTS: Grouping of inhalable and dermal exposure based on exposure determinants resulted in the highest, but still modest, contrast (epsilon approximately 0.3). Classifying subjects based on a combination of plant and department resulted in a slightly lower contrast (epsilon approximately 0.2). If the determinant based grouping derived from the 1997 exposure survey was used to classify workers in the 1988 survey the average contrast decreased significantly for both exposures (epsilon approximately 0.1). On the contrary, the exposure classification based on plant and department increased in contrast (from epsilon approximately 0.2 to epsilon approximately 0.3) and retained its relative ranking overtime. CONCLUSIONS: Although determinant based groupings seem to result in more efficient groupings within a cross-sectional survey, they have to be used with caution as they might result in significant less contrast beyond the studied population or time period. It is concluded that a classification based on plant and department might be more desirable for retrospective studies in the rubber manufacturing industry, as they seem to have more historical relevance and are most likely more accurately recorded historically than information on exposure determinants in a particular industry.
BACKGROUND: The authors recently developed a Dermal Exposure Assessment Method (DREAM), an observational semiquantitative method to assess dermal exposures by systematically evaluating exposure determinants using pre-assigned default values. AIM: To explore the accuracy of the DREAM method by comparing its estimates with quantitative dermal exposure measurements in several occupational settings. METHODS: Occupational hygienists observed workers performing a certain task, whose exposure to chemical agents on skin or clothing was measured quantitatively simultaneously, and filled in the DREAM questionnaire. DREAM estimates were compared with measurement data by estimating Spearman correlation coefficients for each task and for individual observations. In addition, mixed linear regression models were used to study the effect of DREAM estimates on the variability in measured exposures between tasks, between workers, and from day to day. RESULTS: For skin exposures, spearman correlation coefficients for individual observations ranged from 0.19 to 0.82. DREAM estimates for exposure levels on hands and forearms showed a fixed effect between and within surveys, explaining mainly between-task variance. In general, exposure levels on clothing layer were only predicted in a meaningful way by detailed DREAM estimates, which comprised detailed information on the concentration of the agent in the formulation to which exposure occurred. CONCLUSIONS: The authors expect that the DREAM method can be successfully applied for semiquantitative dermal exposure assessment in epidemiological and occupational hygiene surveys of groups of workers with considerable contrast in dermal exposure levels (variability between groups >1.0). For surveys with less contrasting exposure levels, quantitative dermal exposure measurements are preferable.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Although the main risk factor is smoking, 15-19% of COPD even in smokers has been attributed to occupational exposures. The aim of this study was to investigate the association between occupational exposure and risk of COPD. METHODS: Participants were part of a cross sectional study of risk factors for COPD. A total of 1232 completed a detailed respiratory questionnaire, spirometric testing and measurement of gas transfer. Job histories were coded according to the International Standard Classification of Occupations. These codes were then used to establish occupational exposures using the ALOHA job exposure matrix. RESULTS: The prevalence of emphysema was 2.4%, chronic obstructive bronchitis 1.8%, and COPD 3.4%. Subjects ever exposed to biological dusts had an increased risk of chronic obstructive bronchitis (OR 3.19; 95% CI 1.27 to 7.97), emphysema (OR 3.18; 95% CI 1.41 to 7.13), and COPD (OR 2.70, 95% CI 1.39 to 5.23). These risks were higher in women than in men. For biological dust, the risk of emphysema and COPD was also significantly increased in both the duration of exposure categories, again in women but not in men. No significant increased risks for COPD were found for mineral dust (OR 1.13; 95% CI 0.57 to 2.27) or gases/fumes (OR 1.63; 95% CI 0.83 to 3.22). CONCLUSION: In this general population sample of adults, occupational exposures to biological dusts were associated with an increased risk of COPD which was higher in women. Preventive strategies should be aimed at reducing exposure to these agents in the workplace.
AIMS: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). METHODS: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (>/=25 revertants/cm(2)), low (<25 revertants/cm(2))) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (>/=210 revertants/m(3)), low (<210 revertants/m(3))). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. RESULTS: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. DISCUSSION: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry.
Mutagenic exposure conditions in several rubber manufacturing companies (n=9) in The Netherlands were studied. Mutagenicity of total suspended particulate matter in air (TSPM) and of wipe samples from possible contact surfaces were measured in the Ames mutagenicity assay with Salmonella typhimurium YG1041 in the presence of a metabolic activation system. Large differences in median mutagenicity of TSPM samples were observed between companies (range 49-1056rev/m(3)) and to a lesser extent between production functions (range 129-402rev/m(3)). The production function curing revealed overall the highest TSPM mutagenicity levels. Forty-one percent of the surface wipe samples revealed mutagenic activity ranging from 26 to 665rev/cm(2). Mixing had the largest proportion of positive samples resulting in a median surface mutagenic contamination of 39rev/cm(2). Surface mutagenic contamination, averaged per department/company combination, showed only a weak correlation with TSPM mutagenicity (r=0.28, P=0.05). Company, production function and total soluble matter (e.g. mass collected upon extraction with organic solvents with different polarity) explained 79 and 81% of the variability in mutagenicity of TSPM and surface contamination levels, respectively. "Company" was identified as the most important exposure determinant for mutagenic activity in TSPM and surface wipe samples. This indicates the importance of company specific determinants like production volume and rubber chemicals used for the encountered mutagenic exposure conditions. Detection of substantial mutagenic activity on possible contact surfaces supports furthermore the potential importance of the dermal route in the uptake of genotoxic compounds of workers in the rubber manufacturing industry.
Skin diseases, such as hand dermatitis, are thought to be a common problem in the rubber manufacturing industry, as workers are exposed to a wide range of chemicals with known irritant and sensitizing potential. We conducted a cross-sectional survey of a representative sample of rubber manufacturing workers (N = 202), selected from nine different rubber companies. Prevalence of hand dermatitis ("major" and "minor" dermatitis) and skin injuries was assessed on the basis of a diagnosis by a dermatologist. We investigated the possible relations between actual skin exposure, handwashing practices, and hand dermatitis. Prevalence of major hand dermatitis (7%) was comparable with that in the general population; however, minor signs of dermatitis were more common among the surveyed population (28%), as were traumata of the skin (17%). Dermal exposure to cyclohexane-soluble agents at work was related to the occurrence of major hand dermatitis, but not to the occurrence of minor hand dermatitis. Moderate and frequent handwashing especially with industrial surfactants containing scrubbing particles were found to be strongly associated with the occurrence of minor dermatitis [odds ratio = 4.27 (95% confidence interval = 0.90-20.27) and odds ratio = 6.38 (95% confidence interval = 1.33-30.17, respectively)].
A database of dermal exposure measurements (DERMDAT) comprising data from 20 surveys was created. The majority of dermal exposure measurements were from agricultural settings in which workers' exposure to pesticides was investigated. Other data came from studies of workers exposed to polycyclic aromatic hydrocarbons (e.g. coke-oven workers and paving workers) and from studies of subjects exposed to complex mixtures (rubber industry). The database contains approximately 6400 observations. Grouping the workers by job title, factory and body location and excluding groups with more than 25% data below the limit of detection, or with less than two workers with at least two repeats, resulted in 283 groups with 1065 workers and 2716 measurements. Analyses of variability showed median values of the total, within- and between-worker geometric standard deviations of respectively 2.55, 1.98 and 1.47, strikingly similar to what has been published previously for respiratory exposure. Within-worker variability ((w)S(2)y) was in general higher than between-worker variability ((b)S(2)y) in dermal exposure levels. Agricultural groups of re-entry workers showed very little to no between-worker variability, while industrial groups did show some variability in individual mean exposures (range (b)S(2)y=0.15-0.29). When the between-body-location component (bl)S(2)y) was also addressed, it turned out to be the most prominent component (median (b)S(2)y=0.004; median (w)S(2)y=0.12; median (bl)S(2)y=0.34). In agriculture the between-body-location component was smaller than in industry. Day-to-day variability in dermal exposure levels appeared to be significant for specific locations, but not for the average of several body-location. Underlying exposure scenarios (transfer and deposition) also played an important role.
We present measurements of absorption by the 21 cm hyperfine transition of neutral hydrogen toward radio sources at substantial look-back times. These data are used in combination with observations of rotational transitions of common interstellar molecules to set limits on the evolution of the fine structure constant: alpha/ alpha<3.5x10(-15) yr(-1), to a look-back time of 4.8 Gyr. In the context of string theory, the limit on the secular evolution of the scale factor of the compact dimensions, R, is &Rdot/ R<10(-15) yr(-1). Including terrestrial and other astronomical measurements places 2sigma limits on slow oscillations of R from the present to the epoch of cosmic nucleosynthesis, just seconds after the big bang, of DeltaR /R<10(-5).
The aim of this study was to evaluate current mutagenic activity of ambient rubber dust and fume exposure in the mixing and curing departments of two rubber tire companies situated in The Netherlands and Sweden. Salmonella typhimurium strains YG1021, YG1024 and YG1041 were used to study the possible presence of mutagenic nitroarenes and aromatic amines. A large difference in mutagenic activity was found between the two companies. While the rubber tire company situated in The Netherlands revealed overall high mutagenic activity of rubber dust and fumes in the mixing and curing departments, respectively, 430 and 279 rev/m(3) (YG1041), the Swedish company showed almost no mutagenic activity, respectively, 18 and 54 rev/m(3) (YG1041). Further identification of the mutagenic profile showed that mutagenic activity was exclusively observed in S. typhimurium strains with elevated levels of O-acetyltransferase activity (YG1041 and YG1024) in the presence of a metabolic active liver S9 fraction, possibly indicating the presence of indirect mutagenic aromatic amines. These results show that although production processes and lay-out within rubber tire companies are comparable, differences in rubber chemicals used and overall level of control measures (e.g., good housekeeping, cleanliness) are likely to result in substantial differences in mutagenic exposure levels between companies.
Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of patients treated with anti-neoplastic drugs and particulate phase anti-neoplastic drugs in the air of outpatient and nursing clinics. A new visual scoring technique using a fluorescent tracer was developed. The method showed a very low limit of detection (0.02 microl of contamination) and a very high inter-observer agreement (ICC=0.99). Evaluation of IV systems and connectors showed distinct differences between the systems. It was estimated that 0.5-250 microg of a drug can become available for contamination during each infusion. Differences in average contamination between nurses were negligible in the experimental set-up. Widespread and frequent contamination due to spillage of contaminated urine was revealed and appeared not to be restricted to the patient's room. Airborne particulate concentrations went undetected for 80% of the measurements. However, in a few cases concentrations up to 2 ng/m(3) of cyclophosphamide were measured predominantly in a room of a patient treated with this anti-neoplastic drug. Based on these results and a recently proposed conceptual model for dermal exposure a most likely exposure scenario was postulated both for nurses involved in administering drugs and nurses caring for treated patients. Estimation of all relevant mass transport rates will be a challenge for the near future.
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We have developed a stable isotope breath test to trace physiological remnant metabolism. Validity of the test depends on the injected lipid emulsion mimicking chylomicron remnant (CR) clearance and on subsequent metabolism of the emulsion cholesteryl ester (CE). Oxidation of CE fatty acids could involve both mitochondrial and peroxisomal pathways. In the present studies various agents were used to inhibit the binding of remnants, CE hydrolysis or mitochondrial fatty acid oxidation. Treatment of mice with suramin or lactoferrin markedly delayed the clearance and metabolism of remnants as shown by the significantly lower enrichment of 13CO(2) in the breath when compared with untreated mice. In hepatectomized rats injected with remnant-like emulsions, enrichment with 13CO(2) was virtually abolished. Treatment of mice with chloroquine or rats with methyl palmoxirate (an inhibitor of mitochondrial fatty acid oxidation) markedly impaired the recovery of label in the breath. Compared with mice fasted overnight, Intralipid by gavage decreased the breath enrichment with 13CO(2) consistent with competition between endogenous CR and the injected emulsion particles. These findings show that the breath test reliably measures the metabolism of CR and that CE fatty acid is metabolised by mitochondrial pathways.
In this study, the applicability of a symptom-based questionnaire on hand dermatitis was assessed in a population of rubber workers. The questionnaire was previously validated in a study among nurses. 224 subjects employed in 9 different companies completed a questionnaire on skin complaints. Subsequently, 202 workers attended the physical examination of the skin by a dermatologist. The ascertainment of skin complaints according to the questionnaire was compared to the medical evaluation. The 2 different diagnostic tools used for assessing dermatitis resulted in dissimilar estimates of the prevalence of active hand dermatitis, ranging from 6.9% to 38.1% of all workers. Using the medical evaluation as 'gold standard' we observed a moderate sensitivity and specificity (respectively 71.4%; 95% CI: 47.7-95.1 and 76.1%; 95% CI: 70.0-82.2), a low positive predictive value (18.2%; 95% CI: 8.0-28.4) and a high negative predictive value (97.3%; 95% CI: 94.7-99.9) for the classification based on the self-administered questionnaire. When evaluated against 'first symptoms of dermatitis' the sensitivity decreased, while the specificity remained almost the same. The deviant findings between the present and the original validation study of the same questionnaire among nurses hamper its applicability in populations with different occupations. Therefore, if questionnaires are to be used, validity studies have to be carried out to evaluate differences in perception of skin diseases between different (occupational) populations.
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Exposure to inhalable particulates and dermal exposure to cyclohexane soluble matter (CSM) were evaluated in seven rubber manufacturing companies in 1988 and 1997. The identified exposure trends were used to study the effectiveness of control measures implemented over a nine-year period. Sampling and analytical methodologies were identical in both surveys. Inhalable particulate exposure was measured with a PAS6 sampling head. Dermal exposure was assessed by means of a dermal pad sampler worn at the lower wrist of the hand of preference. Changes in working organization and control measures taken after 1988 were identified based on discussions with management representatives and two walk-through surveys performed in 1994 and 1997. Exposure data were aggregated for comparison between years both at company and production function level. The mixed effect statistical procedure was used to evaluate the influence of control measures and seniority on current exposure levels. Comparison of the exposure levels between 1988 and 1997 revealed a reduction rate of 5.7 and 6.7% per year for inhalable particulate and dermal exposure, respectively. Companies and production functions with the highest exposure levels in 1988 and workers with seniority (more experience) showed a steeper decline in exposure levels. Fifty-seven control measures, mostly designed to control the levels of inhalable exposure were identified. Elimination of sources significantly reduced the inhalable particulate and dermal exposure by two-thirds of the level of 1988. Reduction of emission did not show a significant overall decrease in exposure concentrations. Control measures designed to control the levels of contaminants showed a significant reduction for both inhalable and dermal exposure, respectively 34 and 49% of the exposure level of 1988. These results indicate that efforts taken to improve work conditions in the rubber manufacturing industry in The Netherlands over this decade have been successful in reducing both inhalable particulate and dermal contamination.