Martie van Tongeren

The INTERPHONE study: design, epidemiological methods, and description of the study population

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case–control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case–control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

Mobile phone use and risk of glioma in adults: case-control study

Abstract Objective To investigate the risk of glioma in adults in relation to mobile phone use. Design Population based case-control study with collection of personal interview data. Setting Five areas of the United Kingdom. Participants 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists. Main outcome measures Odds ratios for risk of glioma in relation to mobile phone use. Results The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use. Conclusions Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias.

Occupational cancer burden in Great Britain

A sound knowledge base is required to target resources to reduce workplace exposure to carcinogens. This project aimed to provide an objective estimate of the burden of cancer in Britain due to occupation. This volume presents extensive analyses for all carcinogens and occupational circumstances defined as definite or probable human occupational carcinogens by the International Agency for Research on Cancer. This article outlines the structure of the supplement – two methodological papers (statistical approach and exposure assessment), eight papers presenting the cancer-specific results grouped by broad anatomical site, a paper giving industry sector results and one discussing work-related cancer-prevention strategies. A brief summary of the methods and an overview of the updated overall results are given in this introductory paper. A general discussion of the overall strengths and limitations of the study is also presented. Overall, 8010 (5.3%) total cancer deaths in Britain and 13, 598 cancer registrations were attributable to occupation in 2005 and 2004, respectively. The importance of cancer sites such as mesothelioma, sinonasal, lung, nasopharynx, breast, non-melanoma skin cancer, bladder, oesophagus, soft tissue sarcoma and stomach cancers are highlighted, as are carcinogens such as asbestos, mineral oils, solar radiation, silica, diesel engine exhaust, coal tars and pitches, dioxins, environmental tobacco smoke, radon, tetrachloroethylene, arsenic and strong inorganic mists, as well as occupational circumstances such as shift work and occupation as a painter or welder. The methods developed for this project are being adapted by other countries and extended to include social and economic impact evaluation.

Conceptual model for assessment of inhalation exposure to manufactured nanoparticles

As workplace air measurements of manufactured nanoparticles are relatively expensive to conduct, models can be helpful for a first tier assessment of exposure. A conceptual model was developed to give a framework for such models. The basis for the model is an analysis of the fate and underlying mechanisms of nanoparticles emitted by a source during transport to a receptor. Four source domains are distinguished; that is, production, handling of bulk product, dispersion of ready-to-use nanoproducts, fracturing and abrasion of end products. These domains represent different generation mechanisms that determine particle emission characteristics; for example, emission rate, particle size distribution, and source location. During transport, homogeneous coagulation, scavenging, and surface deposition will determine the fate of the particles and cause changes in both particle size distributions and number concentrations. The degree of impact of these processes will be determined by a variety of factors including the concentration and size mode of the emitted nanoparticles and background aerosols, source to receptor distance, and ventilation characteristics. The second part of the paper focuses on to what extent the conceptual model could be fit into an existing mechanistic predictive model for ‘‘conventional’’ exposures. The model should be seen as a framework for characterization of exposure to (manufactured) nanoparticles and future exposure modeling.

History of allergies and risk of glioma in adults

Epidemiological studies have consistently reported an inverse association between a history of allergic disease and risk of glioma. The reason for this association is unclear, and there is a lack of studies with the detail and size to explore the association in depth. We conducted a UK population‐based case‐control study with 965 glioma cases and 1,716 controls to investigate glioma risk in relation to allergic disease. Risk was reduced in subjects reporting a history of asthma (odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.54–0.92), hay fever (OR = 0.73, 95% CI: 0.59–0.90), eczema (OR = 0.74, 95% CI: 0.56–0.97) and other allergies (OR = 0.65, 95% CI: 0.47–0.90). Risk was reduced for all the main histological groups. There was no significant trend of risk with age, at the onset of each condition, or the number of conditions reported. Risk reductions were strongest for asthma or hay fever with recent onset. Risk in asthmatic subjects was not related to frequency of use of antiasthmatic drugs, but was significantly reduced for use of antiallergenic medication among subjects with hay fever. The study showed an inverse association of glioma risk with allergic disease. Possible reasons for the association, as well as potential immunological aetiology, include confounding, bias and reverse causality.

Assessing exposure misclassification by expert assessment in multicenter occupational studies

Background: In a multicenter case-control study of lung cancer in central and eastern Europe and in Liverpool, exposure to occupational agents was assessed by teams of local experts. We performed an interteam agreement study to estimate the levels of exposure misclassification and the expected attenuation of the risk estimate. Methods: Eight teams of experts and a reference rater assessed exposure to 70 putative lung carcinogens for 19 jobs. Agreement among teams was calculated through Cohen’s kappa, sensitivity, and specificity. Results: Each team showed an overall fair to good agreement with the reference (kappa between 0.53 and 0.64). The agreement among teams in the presence of exposure was excellent for 9 agents, fair to good for 16, and poor for 29. For all agents the specificity was high (average 0.94), although sensitivity varied considerably. Conclusions: This study of expert exposure assessment showed a small range in reliability among teams of experts, but large differences among agents. This paper presents the range in levels of misclassification that can be expected using experts for assessing occupational exposure to different agents, and the attenuation of the odds ratio that can be expected to result from this misclassification.

Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case–control study

Objectives Retrospective exposure assessment remains a problematic aspect of population-based case–control studies. Different methods have been developed, including case-by-case expert assessment and job–exposure matrices (JEM). The present analyses compare exposure prevalence and risk estimates derived by different exposure assessment methods. Methods In the context of a case–control study conducted in seven European countries, exposure was estimated for asbestos, diesel motor emissions (DME) and crystalline silica, using three different assessment methods. First, experts assigned exposures to all reported jobs on a case-by-case basis. Second, a population-specific JEM (PSJEM) was developed using the expert assessments of controls only, and re-applied to all study subjects. Third, an independent general population JEM (GPJEM) was created by occupational exposure experts not involved in the original study, and applied to study subjects. Results from these methods were compared. Results There was poor to fair agreement in assigned exposure between expert assessment and the GPJEM (kappas: asbestos 0.17; DME 0.48; silica 0.38). Exposure prevalence was significantly heterogeneous (p<0.01) between countries for all three agents and assessment methods. For asbestos and DME, significant country heterogeneity in risk estimates was observed when using expert assessment. When applying the GPJEM, the heterogeneity in risk estimates for asbestos and, to some extent, silica diminished. Conclusions It has been previously advocated that the expert assessment approach to assign exposures based on detailed questionnaire responses provides more accurate exposure estimates than JEM-based results. However, current results demonstrated little, if any, advantage of case-by-case assessment when compared to a JEM approach.

Grouping and Read-Across Approaches for Risk Assessment of Nanomaterials

Physicochemical properties of chemicals affect their exposure, toxicokinetics/fate and hazard, and for nanomaterials, the variation of these properties results in a wide variety of materials with potentially different risks. To limit the amount of testing for risk assessment, the information gathering process for nanomaterials needs to be efficient. At the same time, sufficient information to assess the safety of human health and the environment should be available for each nanomaterial. Grouping and read-across approaches can be utilised to meet these goals. This article presents different possible applications of grouping and read-across for nanomaterials within the broader perspective of the MARINA Risk Assessment Strategy (RAS), as developed in the EU FP7 project MARINA. Firstly, nanomaterials can be grouped based on limited variation in physicochemical properties to subsequently design an efficient testing strategy that covers the entire group. Secondly, knowledge about exposure, toxicokinetics/fate or hazard, for example via properties such as dissolution rate, aspect ratio, chemical (non-)activity, can be used to organise similar materials in generic groups to frame issues that need further attention, or potentially to read-across. Thirdly, when data related to specific endpoints is required, read-across can be considered, using data from a source material for the target nanomaterial. Read-across could be based on a scientifically sound justification that exposure, distribution to the target (fate/toxicokinetics) and hazard of the target material are similar to, or less than, the source material. These grouping and read-across approaches pave the way for better use of available information on nanomaterials and are flexible enough to allow future adaptations related to scientific developments.

A cohort mortality study of U.K. carbon black workers, 1951–1996

BACKGROUND Carbon black, a powdered form of elemental carbon is used in the manufacture of rubber products, paints, plastics, and inks. In 1974, the Health and Safety Executive initiated a cohort mortality study on possible carcinogenic effects on carbon black workers. METHODS The mortality of a cohort of 1,147 male manual workers from five U.K. factories manufacturing carbon black was investigated for the period 1951-1996. All subjects were employed in the carbon black industry for 12 months or more, and all were first employed before 1975. Limited work histories were used to calculate estimates of individual cumulative exposure to carbon black, using a job-exposure matrix derived by the study team. RESULTS Based on serial rates for the general population of England and Wales, significantly elevated mortality was observed in the main study cohort for all causes (Obs 372, Exp 328.7, SMR 113, P < 0.05) and for lung cancer (Obs 61, Exp 35.3, SMR 173, P < 0.001). There were highly elevated lung cancer SMRs at two of the factories, and unexceptional SMRs at the remaining three factories. There was no indication of lung cancer SMRs increasing with period from first employment. Poisson regression analyses failed to find significant trends of lung cancer risks increasing either with cumulative exposure to carbon black (4 levels) or with duration of employment at the participating factories (4 levels). CONCLUSIONS Confident interpretation of the elevated SMRs found for lung cancer in two of the factory subcohorts is not possible but the study has been unable to link cumulative exposure to carbon black with elevated risks of lung cancer.

Levels of second hand smoke in pubs and bars by deprivation and food-serving status: a cross-sectional study from North West England

BackgroundThe UK government proposed introducing partial smokefree legislation for England with exemptions for pubs and bars that do not prepare and serve food. We set out to test the hypothesis that pubs from more deprived areas and non food-serving pubs have higher levels of particulate air pollution.MethodsWe conducted a cross sectional study in four mainly urban areas of the North West of England. We recruited a stratified random sample of 64 pubs divided into four groups based on whether their local population was affluent or deprived (using a UK area based deprivation measure), and whether or not they served food. The timing of air quality monitoring stratified to ensure similar distribution of monitoring by day of the week and time of evening between groups. We used a portable air quality monitor to collect fine particle (PM2.5) levels over a minimum of 30 minutes in areas where smoking was allowed,, and calculated mean time-time weighted average PM2.5 levels.ResultsMean PM2.5 was 285.5 μg/m3 (95% CI 212.7 to 358.3). Mean levels in the four groups were: affluent food-serving pubs (n = 16) 188.1 μg/m3 (95%CI 128.1 to 248.1); affluent non food-serving (n = 16) 186.8 μg/m3 (95%CI 118.9 to 254.3); deprived food-serving (n = 17) 399.4 μg/m3 (95%CI 177.7 to 621.2); and deprived non food-serving (n = 15) 365.7 μg/m3 (195.6 to 535.7). Levels were higher in pubs in deprived communities: mean 383.6 μg/m3 (95% CI 249.2 to 518.0) vs 187.4 μg/m3 (144.8 to 229.9); geometric mean 245.2 μg/m3 vs 151.2 μg/m3 (p = 0.03). There was little difference in particulate levels between food and non food-serving pubs.ConclusionThis study adds to the evidence that the UK government’s proposals for partial smokefree legislation in England would offer the least protection to the most heavily exposed group - bar workers and customers in non food-serving pubs in deprived areas. The results suggest these proposals would work against the UK government’s stated aim to reduce health inequalities.