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Biomedical subjects

J M Meijers

Publications and source records attributed to J M Meijers.

At least 19 recordsLinked to original sources

The predictive value of animal data in human cancer risk assessment.

Carcinogenic effects of chemicals can be investigated in animal experiments and epidemiological studies of exposed humans, mostly in the workplace. In this article epidemiologic evidence is compared with the animal data for 35 chemicals. Risk calculations are compared for 22 chemicals. The chemicals showing no or unclear carcinogenic effects in humans were more likely to show toxic side effects in the animal studies, indicating that the test concentrations were above the maximum tolerated dose. In addition, the animal experiments with these chemicals more often showed neoplastic effects on multiple sites than chemicals for which clear positive epidemiological studies are available. These findings may explain the existence of discrepancies between the outcomes of animal testing and human studies. They suggest that carcinogenic effects in multiple organs in animals could be seen as ultimate manifestations of the side effects of the testing method and that they have limited predictive value for the human situation.

Animals↗

Mortality of Dutch coal miners in relation to pneumoconiosis, chronic obstructive pulmonary disease, and lung function.

OBJECTIVES: To analyse the mortality patterns of former Dutch coal miners, focusing on coal workers' pneumoconiosis (CWP) and chronic obstructive pulmonary diseases (COPD) in relation to pre-existing impairment of lung function. METHODS: 3790 selected miners, medically examined between 1952 and 1963, were followed up to the end of 1991 with the municipal population registries and the causes of death from the death certificates were ascertained and converted to the codes from the ninth revision of the international classification of diseases (ICD-9). Mortality comparisons were made with the male population in The Netherlands, resulting in standardised mortality ratios (SMRs). 3367 miners had radiological manifestation of CWP at medical examinations. RESULTS: 80% of the miners died during the follow up period. Excess mortalities from CWP (SMR 4523) and COPD (SMR 179) were found. Coal miners without CWP also showed an increased mortality from COPD (SMR 2913). A diminished lung function (forced expiratory volume in one second (FEV1), or FEV1/FVC (forced vital capacity) ratio) at medical examination resulted in a significantly increased SMR for COPD (322 and 212 respectively) whereas normal lung function yielded expected mortalities from COPD. A positive correlation also emerged between diminished lung function and the SMR due to CWP. The body mass index (BMI) at the moment of medical examination was correlated with the risk of dying of COPD and CWP: a decreasing BMI resulting in an increased SMR. CONCLUSIONS: Not only infectious diseases and CWP but also COPD is an important cause of occupational mortality in miners with extensive exposure to coal mine dust. No obvious connection between pre-existing CWP and the COPD mortality exists. Impaired FEV1 and FEV1/FVC ratios are predictors of an increased risk of COPD death. The BMI seems to indicate the severity of the COPD, resulting in premature death.

Adult↗

Mortality and lung cancer in ceramic workers in The Netherlands: preliminary results.

A retrospective cohort study in 1794 male ceramic workers in the Netherlands was carried out to analyze the lung cancer risk in relation to crystalline silica exposure and silicosis. They had all been employed for two years or longer in ceramic industries between 1972 and 1982. During a health survey, 124 cases of simple pneumoconiosis were diagnosed; after 14 years of follow-up, 161 deaths had occurred. No increased overall and cause-specific mortality was found in the total group of ceramic workers, and a statistically significant cumulative dose-response relation for silica exposure and lung cancer did not emerge. An excess lung cancer mortality appeared among workers with simple pneumoconiosis. The authors conclude that the disease process resulting in silicosis in the ceramic industry carries an increased risk of lung cancer, which is supportive of a nongenotoxic pathway.

Adult↗

Risk of gastric cancer in pneumoconiotic coal miners and the effect of respiratory impairment.

OBJECTIVES: This study was carried out to investigate the mortality patterns in a group of 3790 coal miners. The study population had abnormal chest x ray films at a routine medical examination that was performed in the 1950s. METHODS: The total group of 3790 coal miners were followed up for mortality up to 1 January 1992. Causes of death, determined and coded at time of death, were traced with help from the Central Bureau of Statistics. RESULTS: Total mortality in this group of coal miners with abnormal chest x ray films was significantly higher than expected (SMR 127.1, 95% CI 122.5-131.6), mainly a reflection of the increase in mortality from non-malignant respiratory disease (SMR 411.0, 95% CI 382.3-441.3). Mortality from gastric cancer was also significantly increased (SMR 147.5, 95% CI 122.3-176.3). This risk of mortality from gastric cancer was confined to workers with no pneumoconiosis or only a mild form. Despite the strong relation to duration of employment and pneumoconiosis the group of workers with more severe manifestations of pneumoconiosis did not experience an excess in mortality from gastric cancer. CONCLUSION: This study confirms the earlier reported risk of gastric cancer in coal miners. Also it confirms the hypothesis that this risk of gastric cancer is limited to workers with a mild degree of pneumoconiosis or none. In workers with severe forms of pneumoconiosis the pulmonary clearance system is impaired in such a way that the inhaled coal dust does not reach the digestive tract.

Adult↗

Cancer mortality and residence near electricity transmission equipment: a retrospective cohort study.

Several studies in recent years have raised the possibility that exposure to extreme low frequency (ELF) electromagnetic fields may be hazardous to human health, in particular by the promotion or initiation of leukaemia and other cancers. To determine if this exposure creates a long-term hazard to the public, the mortality of a group of people identified as having lived in an urban quarter of Maastricht in which two 150 kiloVolt (kV) powerlines and one transformer substation are located was investigated. Using the Dutch population registry it was possible to identify retrospectively 3549 inhabitants of the quarter who lived there for at least 5 years between 1956 and 1981. Of these 1552 study subjects lived within 100 m of the electricity transmission equipment and were exposed to magnetic field intensity of 1.0-11.0 milliGauss. The overall standardized mortality ratio and cancer mortality ratios were either not or only slightly elevated. The study does not support previously reported associations of exposure to ELF electromagnetic fields with leukaemia, brain cancer and breast cancer.

Cause of Death↗

Occupational epidemiological studies in risk assessment and their relation to animal experimental data.

The role of epidemiological and animal experimental studies in the process of qualitative and quantitative risk assessment is discussed. So far little agreement exists between animal experimental data and epidemiological outcomes in the procedure of qualitative risk assessment. Several reasons for these discrepancies are mentioned. The application of existing epidemiological study results in quantitative risk assessment is hampered by factors, such as the lack of exact exposure information (compound, level, duration), undefined other exposures in and outside the working environment, small sample sizes, the comparatively short duration of epidemiological studies and the absence of detailed information about the specific effects. All this resulted in a relatively small impact of epidemiological studies in risk assessment. Recommendations are made in order to improve the impact of epidemiology in risk assessment.

Animals↗

[Course and distribution of mortality of pleural mesothelioma in The Netherlands, 1970-1987].

In this article the sex- and age-specific trends and geographical distribution of asbestos related pleural mesothelioma mortality in the Netherlands between 1970 and 1987 are investigated. For men total mortality increased from 10.8 per million during 1970-1978 to 20.9 per million during 1979-1987. The highest mortality occurred with 147.7 per million in 1987 in the age group between 65 and 74 years. Mortality rates for the age group between 55 and 64 years amounted to 96.5 per million in 1987. The geographical distribution over the country showed a strong concentration of male mesothelioma cases in the regions with many harbours, shipyards and heavy industries round Amsterdam, IJmuiden, Rotterdam, Dordrecht and Walcheren. Using linear regression techniques, it was calculated that several thousands new mesothelioma cases will occur in the Netherlands during the next two decades. A significant decrease in mesothelioma mortality can not be expected before 2010.

Adult↗

Long-term mortality in miners with coal workers' pneumoconiosis in The Netherlands: a pilot study.

In order to investigate whether the prolonged exposure to coal mine dust increases the cancer risk for coal miners, a pilot study in a selected cohort of 334 Dutch miners with coal workers' pneumoconiosis (CWP), followed from 1956 until 1983, was conducted. In total, 165 miners had died (49.4%); for 162 (98.2%) the cause of death was traced. In comparison to the general Dutch male population, total mortality in the cohort was statistically significantly increased (SMR: 153). This was in general due to the significantly higher than expected cancer mortality (SMR: 163), cancer of stomach and small intestine (SMR: 401) and nonmalignant respiratory disease (SMR: 426). The lung cancer mortality was within the expected range.

Adult↗

Neuropsychiatric disorders among solvent-exposed workers. First results from a Dutch case-control study.

This case-control study was undertaken to determine whether exposure to organic solvents, as experienced by Dutch painters, causes an increased risk of disability due to neuropsychiatric disorders. Cases and controls were selected from the Dutch Painters' and Construction Workers' Organizations. Cases were defined as male persons receiving disability benefits due to neuropsychiatric disorders. The controls consisted of a random sample of 1000 male persons from the total study population. Cases (n = 252) and controls (n = 822) participated in our study by returning the completed questionnaires. The questionnaire was used to collect information about occupational history and the presence of potentially confounding factors. The adjusted Odds Ratio for the total group of neuropsychiatric disorders did not reach a statistically significant level (OR = 1.17; P less than 0.30). Although a stronger association was suggested between "neuroses" (ICD 300) and exposure to organic solvents (OR = 2.30; P less than 0.05), there are indications that this relationship is merely the result of classification bias. The results of this study do not confirm, but also do not completely exclude, that Dutch painters are at increased risk of being prematurely disabled due to neuropsychiatric disorders.

Adult↗

Silica exposure and lung cancer in ceramic workers: a case-control study.

The results are presented from a case-control study, concerning the possible relation between silica exposure in the Dutch fine ceramic industry and lung cancer. For this purpose 381 male, age-matched pairs of primary lung cancer cases and controls were selected from the pathology department of the University Hospital in the region, where two large ceramic companies are located. Information about employment in the ceramic industry was obtained from the personnel and financial administration departments of the two companies. On the basis of job titles a panel of occupational hygiene experts reached consensus about the qualitative exposures of each individual worker. Twenty one per cent of the cases were employed in the ceramic industry, compared with 19% of the controls (odds ratio 1.11; 95% Cl: 0.77-1.61). Although the average employment period of cases and their relative silica exposure surpassed those of controls, odds ratios for long duration of employment and considerable exposure to respirable silica dust did not reach statistical significance. After constructing a qualitative exposure index, based on the amount and duration of exposure, a tendency towards a positive correlation with lung cancer emerged. No relation between specific histological tumour cell types and working in the ceramic industry emerged. Although the study does not suggest a consistent cause-effect relation between silica exposure in the regional, Dutch fine ceramic industry and lung cancer, an increased risk for the high exposure group in the past can not be totally excluded.

Adenocarcinoma↗

Trends and geographical patterns of pleural mesotheliomas in the Netherlands 1970-87.

The sex and age related trends and geographical distribution of asbestos related mortality from pleural mesothelioma in the Netherlands between 1970 and 1987 were investigated. Deaths from pleural malignancies recorded by the Dutch Central Bureau of Statistics (CBS) were used and death rates were age adjusted per year by the indirect method. Standardised mortality ratios (SMRs) were computed for 43 regions over the period 1979-86. For men, total mortality increased from 10.8 per million in the period 1970-8 to 20.9 per million during 1979-87. The highest mortality occurred in the group aged between 65 and 74 with 147.7 per million in 1987. The death rate for the group aged between 55 and 64 was 96.5 per million in 1987. For women, total death rates for pleural mesothelioma showed a moderate increase from 2.5 per million in the period 1970-8 to 3.6 per million during 1979-87. The highest mortality occurred in the group aged over 65, fluctuating around 10-15 per million. For men and women under 45 mortality was very low and presented no upward trend. The geographical distribution over the country for the period 1979-86 showed a pattern with a clear concentration of deaths from mesothelioma in men, in conurbations with many harbours, shipyards, and heavy industry near the river mouths and along the North Sea Coast.

Adult↗

Epidemiologic studies of inorganic dust-related lung diseases in The Netherlands.

The results of two epidemiologic investigations on dust-related lung diseases are presented. The two studies had different aims and designs. A cross-sectional study was done to investigate the silicosis prevalence in Dutch fine ceramic workers. In the small ceramic workshops in the Gouda region, simple pneumoconiosis is still commonly present (13.3%), whereas the silicosis prevalence in the highly mechanized industries is low (1.7%). Furthermore, heavy smoking seems to enhance the risk for silicosis after long-term exposure to quartz. A case-control study was performed to analyze the relation between dust exposure in the fine ceramic and coal mining industries and lung cancer. No relation between a work history in the dusty trades and lung cancer emerged, and a correlation with a specific histologic tumor cell type could not be demonstrated. Apparently, workers in the Dutch fine ceramic or coal mining industry have no increased risk of developing lung malignancies.

Case-Control Studies↗

Molecular epidemiology of coal worker's pneumoconiosis: application to risk assessment of oxidant and monokine generation by mineral dusts.

It is generally accepted that fibrotic lung diseases are mediated by macrophage-derived cytokines and growth factors. Basic research continues to find new factors involved in these disease processes to incorporate into new hypotheses. Two hypotheses implicitly generated by recent findings were tested in an epidemiologic approach among workers in coal mines. This approach is described as molecular epidemiology and is exemplified by two studies focused on different mechanistic aspects of coal workers' pneumoconiosis (CWP): antioxidants in red blood cells of miners with CWP and generation of tumor necrosis factor (TNF) by blood monocytes of miners with CWP. Most findings in the antioxidant study may merely be reflections of pulmonary inflammatory processes. Some data in the TNF study indicate, however, that TNF release is a risk factor for the development of lung fibrosis after prolonged exposure to coal mine dust.

Adult↗

Exposure-outcome relationships between organic solvent exposure and neuropsychiatric disorders: results from a Dutch case-control study.

In this article the material collected for a case-control study is analyzed in order to evaluate the existence of relationships between organic solvent exposure and the entitlement to disability benefits due to neuropsychiatric disorders. Questionnaires were used to collect information on 252 cases receiving compensation due to neuropsychiatric disorders and 822 controls about their occupational history and work practices related to organic solvent exposure. In order to estimate the exposure to organic solvents, three exposure indices were used: duration of exposure, painters' index, and general exposure index. Analysis showed some tendencies indicating positive exposure-outcome relationships. Furthermore, some work activities and working conditions associated with high exposure to organic solvents (e.g., poor ventilation, using paint removers) resulted in a marked increase of the likelihood for receiving disability benefits due to neuropsychiatric disorders.

Case-Control Studies↗

Occupational cohort studies: the influence of design characteristics on the healthy worker effect.

A cross-sectional analysis of the relation between the estimated healthy worker effect (HWE), as measured by a total Standardized Mortality Ratio (SMR) less than 100, and relevant design characteristics in 270 published retrospective occupational cohort studies is presented. The majority of the reviewed studies showed a HWE, varying in SMR from 50 to 99 (mean: 84). The estimated HWE seemed to influence the final outcomes of the studies to a great extent. A tendency for a positive relation between the study size in terms of the number of exposed workers, total number of person-years of follow-up, and the HWE emerged. Studies with a comparatively short follow-up period had an increased chance of resulting in a HWE. Cross-sectional cohorts did not show a stronger HWE than open cohorts. Studies of chemical exposures revealed a fivefold excess of having a HWE compared with other studies.

Cohort Studies↗

Risk assessment of leukaemia and occupational exposure to benzene.

Experimental toxicological studies have offered clear evidence that benzene induces haematopoietic neoplasms, and it is generally accepted that exposure to benzene is a risk factor for leukaemia, in particular for acute non-lymphatic leukaemia. Quantitative aspects of benzene risk assessment are still a matter of controversy, however. In several risk assessments an estimated 50 deaths from leukaemia per 1000 deaths would arise from exposures to benzene of 10 ppm during a working life of 30 years. The assessment presented in this paper leads to lower estimates, which are more in agreement with the weak toxicological data. Furthermore, an approach is presented to incorporate the results of low exposure epidemiological studies into the process of quantitative risk assessment.

Benzene↗