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Biomedical subjects

R Vermeulen

Publications and source records attributed to R Vermeulen.

32 records · Page 2Linked to original sources

Dermal exposure assessment.

Assessing dermal exposure is a complex task. Even the most commonly used methods face fundamental problems and there are large gaps in the documentation and validation of sampling methods. Still larger uncertainties exist regarding strategies for measurement. We propose a strategy based on a conceptual model and which draws on the considerable insight gained for airborne contaminants, including EN 689 for assessing exposure by inhalation. The vast amount of air sampling data has provided good insight into the statistical properties of short-term and long-term exposure levels, which is essential for designing cost-effective exposure studies. For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Transport rates away from the skin contaminant layer determine the 'memory' of a dermal sample and measurement principles are proposed depending on these rates. It is argued that uptake is the ultimate dermal exposure metric for risk assessment and should be the basis for devising dermal occupational exposure limits.

Cost-Benefit Analysis↗

Use of qualitative and quantitative fluorescence techniques to assess dermal exposure.

Fluorescent tracers provide a way of simultaneously assessing the mass of a contaminant hazardous substance on the surface of the skin of a worker and the area of skin exposed. These parameters, along with the duration of exposure and the estimated contaminant concentration in the skin contamination layer, can be used to calculate the likely uptake through the skin. Repeated assessment of the mass of tracer on a surface within a room or on the surface of the skin can also allow the net transfer of contaminant to that compartment to be estimated. Qualitative evaluation of transfer processes using fluorescent tracers can help identify important secondary sources of exposure.

Environmental Monitoring↗

Identification of dermal exposure pathways in the rubber manufacturing industry.

Current existing dermal exposure assessment strategies are predominantly based on regulatory protocols. In order to develop effective and efficient strategies more data driven approaches are needed. In a recently developed conceptual model for dermal exposure, compartments, barriers and mass transport processes relevant for dermal exposure were described. We systematically applied this conceptual model to the rubber manufacturing industry to assess dermal exposure to cyclohexane soluble matter (CSM) and used quantitative data to design an exposure assessment strategy. Identification of the spatial distribution of the dermal contamination showed high CSM surface concentrations for the upper body. Moreover, because of the high correlation between dermal exposure at the wrist and calculated total body exposure (r=0.89, P<0.01) an exposure assessment strategy based on only one pad sampler was employed to estimate CSM surface concentrations in the skin contaminant layer. Qualitative and quantitative evaluation of the relevant compartments and related mass transport processes demonstrated the importance of deposition of airborne contaminants and direct transfer of contaminants from sources and surfaces to the skin contaminant layer. Interestingly, the importance of the different exposure pathways varied considerably between production functions. The use of a model driven exposure assessment strategy in the rubber manufacturing industry revealed relevant skin regions, compartments and mass transport processes and enabled development of an effective and efficient strategy for dermal exposure assessment and hazard control in this particular occupational setting.

Bias↗

Weekly patterns in smoking habits and influence on urinary cotinine and mutagenicity levels: confounding effect of nonsmoking policies in the workplace.

Lifestyle factors such as smoking have been shown to influence urinary mutagenicity. Therefore, these factors have to be considered carefully when evaluating occupational genotoxic exposures. We investigated day-to-day variability in active and passive tobacco smoke exposure by studying urinary cotinine levels and determined their influence on observed urinary mutagenicity. Urinary cotinine was assessed for 105 subjects employed in the rubber manufacturing industry in the Netherlands on Sunday, Wednesday, and Thursday. Urinary mutagenicity was measured by the Salmonella typhimurium strain YG1041 with metabolic activation for the Sunday urine sample and a pooled weekday urine sample. A sharp decrease in urinary cotinine concentration was observed during the week compared to Sunday for smokers (39%; P < 0.01) and nonsmokers (23%). Different smoking habits on Sunday resulted in higher regression coefficients for categorical proxies for smoking habits and urinary mutagenicity levels. However, regression coefficients for urinary cotinine and urinary mutagenicity were similar for the Sunday and weekday urine samples (beta = 0.29 and beta = 0.28, respectively). Consequently, these estimates were used to adjust urinary mutagenicity for tobacco smoke intake. Cotinine-adjusted urinary mutagenicity levels were comparable between smokers and nonsmokers, and a similar increase in urinary mutagenicity of 39% and 34%, respectively, was observed for both smokers and nonsmokers due to occupational genotoxic exposures or other changes in lifestyle factors. These results indicate that the introduction of nonsmoking policies in the workplace has reduced exposure to mainstream and environmental tobacco smoke, resulting in a temporal variation in lifestyle-related mutagenicity. Therefore, adequate adjustment for daily tobacco smoke exposure is a necessity when using the urinary mutagenicity assay to evaluate possible genotoxic exposures in the workplace.

Adult↗

Conceptual model for assessment of dermal exposure.

Dermal exposure, primarily to pesticides, has been measured for almost half a century. Compared with exposure by inhalation, limited progress has been made towards standardisation of methods of measurement and development of biologically relevant exposure measures. It is suggested that the absence of a consistent terminology and a theoretical model has been an important cause of this lack of progress. Therefore, a consistent terminology based on a multicompartment model for assessment of dermal exposure is proposed that describes the transport of contaminant mass from the source of the hazardous substance to the surface of the skin. Six compartments and two barriers together with eight mass transport processes are described. With the model structure, examples are given of what some existing methods actually measure and where there are limited, or no, methods for measuring the relevant mass in a compartment or transport of mass. The importance of measuring the concentration of contaminant and not mass per area in the skin contaminant layer is stressed, as it is the concentration difference between the skin contamination layer and the perfused tissue that drives uptake. Methods for measuring uptake are currently not available. Measurement of mass, concentration, and the transport processes must be based on a theoretical model. Standardisation of methods of measurement of dermal exposure is strongly recommended.

Air Pollutants↗

Assessment of occupational exposures in a general population: comparison of different methods.

OBJECTIVES: To evaluate the relative merits of job specific questionnaires and various alternative assessment methods of occupational exposures often used in general population studies. METHODS: Subjects were participants in a hospital based case-control study of risk factors for male infertility. Estimates of exposure to organic solvents and chromium, based on job specific questionnaires, generic questionnaires, self reports of exposure, an external job exposure matrix (JEM), and a population specific JEM were compared with passive diffuse dosimeter results and measurements in urine. Urine samples from the end of the shift were analysed for metabolites of toluene, xylene, several glycol ethers, trichloroethylene, and chromium. Passive dosimeter date, metabolites of specific solvents, and urinary chromium concentrations were available for 89, 267, and 156 subjects, respectively. The alternative methods and measurements in urine were compared by means of the Cohen's kappa statistic and by computing the positive predictive value, sensitivity, and specificity of the alternative methods against measurements in urine. RESULTS: Passive dosimeter results indicated that exposure classifications with job specific questionnaire information could discriminate between high and low exposures. The kappa coefficients were < 0.4, so agreement between the various methods and measurements in urine was poor. Sensitivity of the methods ranged from 0.21 to 0.85, whereas specificity ranged from 0.34 to 0.94. Positive predictive values ranged from 0.19 to 0.58, with the highest values for job specific questionnaires. CONCLUSIONS: The results indicate that the implementation of job specific questionnaires in a general population study might be worth the extra expense it entails, bearing in mind the paramount importance of avoiding false positive exposure estimates when exposure prevalence is low.

Case-Control Studies↗

Pulmonary ventilatory defects and occupational exposures in a population-based study in Spain. Spanish Group of the European Community Respiratory Health Survey.

We assessed the association between occupational exposures and symptoms of chronic bronchitis and pulmonary ventilatory defects in a general population-based study of five areas in Spain. This study forms part of the European Community Respiratory Health Study (ECRHS). Subjects (n = 1,735; age range, 20-44 yr; 52.4% of those initially selected) completed a respiratory questionnaire on symptoms and occupation and underwent baseline spirometry. Occupation was translated with an ad hoc developed job-exposure matrix (EM) into none, low, and high exposure to biological dust, mineral dust, and gases and fumes. Exposure to high levels of biological dust was associated with cough for more than 3 mo (odds ratio [OR], 1.9; p = 0.07), a reduction in FEF(25-27) to 478 ml/s (SD 178), and a reduction in FEV1 to 151 mL (SD 71). These associations remained after excluding subjects with asthma symptoms or bronchial responsiveness. Smokers tended to have a higher risk for respiratory symptoms, but smoking did not modify the association of occupation with pulmonary function. Exposure to mineral dust and gases/fumes was less consistently related to pulmonary function or to respiratory symptoms and this association further decreased after excluding subjects with asthma. In conclusion, exposure to high levels of biological dust in young adults is associated with symptoms of chronic bronchitis and pulmonary ventilatory defects, independently of asthma and smoking.

Adult↗

Disinfectant use as a risk factor for atopic sensitization and symptoms consistent with asthma: an epidemiological study.

Exposure to some nonallergenic compounds has been shown to increase the risk of atopic sensitization and asthmatic symptoms. In order to gain more insight into the largely unknown aetiology of respiratory symptoms in pig farmers, we studied the role of nonallergic exposure. We evaluated associations between chronic respiratory symptoms, specific and total serum immunoglobulin E (IgE) levels, use of disinfectants, and endotoxin exposure levels in a population of 194 Dutch pig farmers. Atopic sensitization (defined as increased production of IgE to common allergens) was found to occur more frequently in farmers who used disinfectants containing quaternary ammonium compounds (QACs) (odds ratio (OR) 7.4; 95% confidence interval (95% CI) 1.3-43.1). ORs for other disinfectants ranged 2.3-4.1 (NS). Atopic sensitization was not found to occur more frequently in farmers with a high endotoxin exposure. The use of disinfectants was only related to respiratory symptoms consistent with asthma in atopics. This is illustrated by the significantly elevated ORs for farmers with IgE to common allergens (house dust mite, grass pollen, birch pollen), and who used disinfectants containing QACs, in the total population and in a subgroup of the total population restricted according to bronchial hyperresponsiveness to histamine (symptomatics with a provocation dose of histamine producing a > or = 10% decrease in forced expiratory volume in one second (PC10) < or = 16 mg.mL-1, compared with asymptomatics with a PC10 > 16 mg.mL-1) (OR 4.4, 95% CI 1.3-14.6; and OR 8.2, 95% CI 1.6-42.6, respectively). Atopy and use of QACs and endotoxin exposure level taken individually were not associated with respiratory symptoms. A combination of atopic sensitization and high endotoxin exposure (> 101 ng.m-3) was strongly associated with respiratory symptoms in the restricted population (OR 6.1; 95% CI 1.0-36.2). Our results suggest that occupational exposure to nonallergenic agents (disinfectants) may induce immunoglobulin E sensitization to common aeroallergens, and that the combination of atopy and exposure to nonallergenic agents (disinfectants and endotoxin) is an important risk factor for development of symptoms consistent with asthma.

Adult↗

Comparison of urine with urethral swabs for the detection of Chlamydia trachomatis in men attending an STD clinic.

Urethral swabs and first-catch urine specimens for the detection of Chlamydia trachomatis were collected from 370 black men with urethritis who attended a sexually transmitted disease (STD) clinic in Pretoria. An enzyme immunoassay (EIA) for C. trachomatis was carried out on all urethral swabs and urine specimens. Chlamydial culture and a direct immunofluorescent antibody (DFA) test (Imagen, Dako, UK) were also carried out on urethral swabs; DFA was used for confirmation of urine EIA positives. Based on culture and/or DFA, C. trachomatis was detected in 96 (26%) urethral swab specimens. The sensitivity of urine EIA investigation was 94% and the specificity 99%, compared with those of urethral swab EIA which were 97% and 99% respectively. The positive and negative predictive values for urine were 96% and 98% compared with 96% and 99% respectively for urethral swabs. Urine examination was therefore sensitive and specific compared with urethral swab examination in these STD patients. In view of this, the advantage of urine as an alternative to urethral swabs for C. trachomatis detection is that sampling is non-invasive and non-traumatic.

Adolescent↗

Covalent dimerization of vascular permeability factor/vascular endothelial growth factor is essential for its biological activity. Evidence from Cys to Ser mutations.

Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is an important factor in the regulation of vascular growth and vascular permeability. VPF is a secreted, dimeric protein and has 8 cysteine residues conserved with platelet-derived growth factor (PDGF). To study the role of some of these cysteine residues in maintaining the structure and function of VPF, we replaced the codons for the second, third, fourth, and fifth cysteine by serine codons, and expressed the mutant proteins in a mammalian expression system. Cysteine residues 2 and 4 in VPF were found to be directly involved in anti-parallel interchain disulfide bonds, as in PDGF. VPF mutants lacking one of these cysteins were severely impaired in their S-linked dimerization, while upon coexpression of both mutants the ability to form dimers was restored. The VPF mutants lacking cysteine residue 2 or 4 also competed poorly for receptor binding of labeled VPF and had low biological activity, but these defects were also complemented by coexpressing the two mutants, indicating that for efficient receptor binding and activation VPF needs to be a covalent dimer, unlike PDGF-BB. Furthermore, cysteine residue 5 was found to be essential for VPF dimerization and activity, while the mutant lacking cysteine residue 3 was only mildly affected in its ability to dimerize and had partial biological activity.

Binding, Competitive↗

Newer beta blockers and the treatment of hypertension.

Beta-adrenoceptor blocking agents are established as one of the principal classes of antihypertensive agents. Despite progressive refinements over the years, they still possess some unwanted effects, which limit their considerable value. In recent years a wide range of variations upon the beta-blocker theme has been developed. The full clinical advantages of the newer agents remain to be defined.

Adrenergic beta-Antagonists↗

Electrocardiographic signs of chronic cor pulmonale in 40 376 patients with silicosis.

The records of all patients who were examined for silicosis at the Fund of Occupational Diseases between 1972 and 1976 are reviewed. In 3627 cases the mechanographical record was incomplete leaving 40 376 patients in the study. Electrocardiographic signs of chronic cor pulmonale (C.C.P.) were detected in 5.58 per cent. The severity of C.C.P. was evaluated and the prevalence of the different electrocardiographic signs was examined. The presence and severity of C.C.P. was compared to the radiological stage of silicosis, to the pulmonary function, to the duration of professional exposure to the risk of silicosis and to the use of tobacco. The value of the electrocardiographic signs of C.C.P. was evaluated. It is concluded that the mechanographical record obtained in insurance medicine is a valuable tool for statistical analysis of a disease and that C.C.P. is an infrequent and mostly late complication of silicosis.

Belgium↗