The UK Childhood Cancer Study: maternal occupational exposures and childhood leukaemia and lymphoma

Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and postnatally. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data.     

WHO's health risk assessment of ELF fields

The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), WHO's scientific collaborating centres (including the UK's National Radiological Protection Board (NRPB)) and over 50 participating Member States are participants of WHO's International EMF Project. As part of WHO's health risk assessment process for extremely low frequency fields (ELF), this workshop was convened by NRPB to assist WHO in evaluating the potential health impacts of electrical currents and fields induced by ELF in molecules, cells, tissues and organs of the body. This paper describes the process by which WHO will conduct its health risk assessment. WHO is also trying to provide information on why exposure to ELF magnetic fields seems to be associated with an increased incidence of childhood leukaemia. Are there mechanisms that could lead to this health outcome or does the epidemiological evidence incorporate biases or other factors that need to be further explored?     

Exposure to electromagnetic fields and the risk of childhood leukaemia: a review

Extremely low-frequency magnetic fields have been classified as possibly carcinogenic to humans, mainly based on epidemiological studies consistently showing an association between long-term average exposures to magnetic fields above 0.3/0.4 microT and the risk of childhood leukaemia. No mechanism to explain this finding has been established and no support for a causal link emerged from experimental studies. Chance or bias cannot be ruled out with reasonable confidence as an explanation for the observed association. If the association is causal, it explains only a small fraction of childhood leukaemia cases. There were some reports of childhood leukaemia clusters in the vicinity of high-power radio and television broadcast transmitters in studies in Australia and Italy. However, recent large-scale systematic studies in Korea and Germany show no association between exposure to radio frequency electromagnetic fields emitted from broadcast towers and childhood leukaemia risk. Studies on mobile phone use and leukaemia risk in adolescents and young adults may be indicated.     

Exposure assessment: implications for epidemiological studies of ionizing radiation

Quantitative estimates of ionizing radiation exposure are often available for use in epidemiological studies. However, depending on the context, the quality of the exposure estimates can vary. For example, the estimates may be specific to individuals in the study or generic values averaged over populations; unavailable for some of the potential study subjects or vary in their form between individuals; based on contemporary measurements or assessed retrospectively; based on measurements alone, on surrogate measures of exposure, or on an exposure assessment model; or, as is often the case, cover one source of radiation exposure rather than all of them. Various ways in which ionizing radiation exposures have been assessed are illustrated through reference to some studies of childhood leukaemia, concerning environmental, medical, natural and parental occupational exposures. Based on this, implications for the interpretation of radiation epidemiological studies are discussed.     

Assessment of environmental exposures from agricultural pesticides in childhood leukaemia studies: challenges and opportunities

Pesticides are ubiquitous in environments of many rural communities due to drift from agricultural applications and home/garden use. Studies of childhood leukaemia predominantly relied on retrospective pesticide exposure assessment and parental recall of use or proximity to fields or pesticide applications. Sample size requirements mostly preclude the collection of individual-level exposure information, biomarkers or environmental measurements of pesticides prospectively in cohorts. Yet such measures can be used in nested case-control approaches or for validating exposure models that can be applied to large populations. Recently developed models incorporate geographic information system technology and environmental databases of pesticide and/or crop data to assess exposure. Models developed in California to estimate residential exposures are presented by linking addresses to agricultural pesticide application data and land-use maps. Results from exposure validation and simulation studies and exposure measurement error issues are discussed.     

Assessment of plutonium exposures for an epidemiological study of US nuclear workers

An ongoing case-control study evaluating the association between workplace external radiation exposures and leukaemia mortality required an assessment of internal plutonium exposures as a potential confounder. Of the study participants, 1,092 were employed at four Department of Energy sites where plutonium-bearing materials were processed or stored. Exposures were assessed by first categorising exposure potentials based on available bioassay data, then estimating doses for workers in the highest categories using recent recommendations of the International Commission on Radiological Protection. Given the aetiology of leukaemia, equivalent dose to active bone marrow was chosen as the exposure variable. There were 556 workers each with at least one plutonium bioassay result, assigned to one of three evaluation categories. Dose estimates were made for 115 workers resulting in a collective equivalent dose of 2.1 person-Sv for 2,822 exposure-years, compared with 29.8 person-Sv estimated from photon exposures. Modelling uncertainties were examined by comparison of results from independent analyses and by Monte Carlo simulation.     

Assessment of occupational exposure to radiofrequency fields and radiation

The use of personal monitors for the assessment of exposure to radiofrequency fields and radiation in potential future epidemiological studies of occupationally exposed populations has been investigated. Data loggers have been developed for use with a commercially available personal monitor and these allowed personal exposure records consisting of time-tagged measurements of electric and magnetic field strength to be accrued over extended periods of the working day. The instrumentation was worn by workers carrying out tasks representative of some of their typical daily activities at a variety of radio sites. The results indicated significant differences in the exposures of workers in various RF environments. A number of measures of exposure have been examined with a view to assessing possible exposure metrics for epidemiological studies. There was generally a good correlation between a given measure of electric field strength and the same measure of magnetic field strength.     

Aetiology of childhood acute leukaemias: current status of knowledge

Acute leukaemia is a consequence of malignant transformation of a haematopoetic progenitor cell. Molecular studies have revealed a prenatal origin of many childhood leukaemias. According to current models, a preleukaemic stem cell clone is generated by a first mutation in utero which, in a minority of children, progresses to leukaemia after receiving further postnatal genetic hits. The nature of pre- and postnatal events involved in leukaemogenesis in children is not well understood. Although genetic predisposition and specific environmental exposures may account for individual cases, the bulk of childhood leukaemia cannot be explained by any of these factors. The higher incidence of the most common leukaemia subtype in affluent societies, as well as the age peak between 2-5 y, suggest a contributory role of socioeconomic factors. An abnormal immune response during delayed exposure to common infections provides a plausible mechanism for malignant progression of preleukaemic clones in a subgroup of children. As highlighted in this review, a common cause for all types and subtypes of childhood leukaemia is highly unlikely. Deeper insights into the pathogenesis of childhood leukaemia will rely on large-scale and combined epidemiological and biomolecular studies.     

50-60 Hz electric and magnetic field effects on cognitive function in humans: a review

This paper reviews the effect of 50-60 Hz weak electric, magnetic and combined electric and magnetic field exposure on cognitive functions such as memory, attention, information processing and time perception, as determined by electroencephalographic methods and performance measures. Overall, laboratory studies that have investigated the acute effects of power frequency fields on cognitive functioning in humans are heterogeneous, in terms of both electric and magnetic field (EMF) exposure and the experimental design and measures used. Results are inconsistent and difficult to interpret with regard to functional relevance for possible health risks. Statistically significant differences between field and control exposure, when they are found, are small, subtle, transitory, without any clear dose-response relationship and difficult to reproduce. The human performance or event related potentials (ERPs) measures that might specifically be affected by EMF exposure, as well as a possible cerebral structure or function that could be more sensitive to EMF, cannot be better determined.     

Assessment of inhomogeneous ELF magnetic field exposures

In daily life as well as at workplaces, exposures to inhomogeneous magnetic fields become very frequent. This makes easily applicable compliance assessment methods increasingly important. Reference levels have been defined linking basic restrictions to levels of homogeneous fields at worst-case exposure conditions. If reference levels are met, compliance with basic restrictions can be assumed. If not, further investigations could still prove compliance. Because of the lower induction efficiency, inhomogeneous magnetic fields such as from electric appliances could be allowed exceeding reference levels. To easily assess inhomogeneous magnetic fields, a quick and flexible multi-step assessment procedure is proposed. On the basis of simulations with numerical, anatomical human models reference factors were calculated elevating reference levels to link hot-spot values measured at source surfaces to basic limits and allowing accounting for different source distance, size, orientation and position. Compliance rules are proposed minimising assessment efforts.     

'Lifestyle' and cancer rates in former East and West Germany: the possible contribution of diagnostic radiation exposures

Breast and prostatic cancer as well as leukaemia in childhood have remarkably increased over some decades in the Federal Republic of Germany as well as in several other highly developed industrial nations. Such increase was much less or not observable in East Germany between 1960 and 1989 where diagnostic exposures were applied to a lesser extent. Low-level radiation can cause these diseases and the difference of cancer rates gives rise to renewed evaluation of current risk estimates. Risk factors for radiation-induced childhood leukaemia and breast cancer are derived from the literature, considering a higher relative biological effectiveness of diagnostic X rays in comparison to the A-bomb gamma rays in Hiroshima and Nagasaki. The prostate is not considered as radiation sensitive by the ICRP. But following a variety of low-level findings in the last two decades it was shown by Myles et al. in the UK that prostatic cancer is inducible by diagnostic X-ray procedures. From their study in men below the age of 60, a doubling dose of about 20 mSv can be estimated. Medical exposures of the considered tissues are taken from published data for East and West Germany. The difference in breast cancer mortality can be explained by diagnostic exposures. The contribution of these to prostatic cancer and childhood leukaemia must be regarded as relevant in current incidences. Reduction of diagnostic exposures would be an important measure for preventing several prominent cancer diseases.     

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny

The European project Alpha-Risk aims to quantify the cancer and non-cancer risks associated with multiple chronic radiation exposures by epidemiological studies, organ dose calculation and risk assessment. In the framework of this project, mathematical models have been applied to the organ dosimetry of uranium miners who are internally exposed to radon and its progeny as well as to long-lived radionuclides present in the uranium ore. This paper describes the methodology and the dosimetric models used to calculate the absorbed doses to specific organs arising from exposure to radon and its progeny in the uranium mines. The results of dose calculations are also presented.     

Transmission lines, EMF and population mixing

Draper et al. found that the incidence of childhood leukaemia was slightly elevated for children living at distances of 200-600 m from high-voltage transmission lines. This elevation cannot be explained by EMF exposure and it is suggested that it may be due to population mixing in housing developments which followed the construction of the lines.     

Neutron measurements at nuclear power reactors [55]

Staff from the Pacific Northwest National Laboratory (operated by Battelle Memorial Institute), have performed neutron measurements at a number of commercial nuclear power plants in the United States. Neutron radiation fields at light water reactor (LWR) power plants are typically characterized by low-energy distributions due to the presence of large amounts of scattering material such as water and concrete. These low-energy distributions make it difficult to accurately monitor personnel exposures, since most survey meters and dosimeters are calibrated to higher-energy fields such as those produced by bare or D₂O-moderated ²⁵²Cf sources. Commercial plants typically use thermoluminescent dosimeters in an albedo configuration for personnel dosimetry and survey meters based on a thermal-neutron detector inside a cylindrical or spherical moderator for dose rate assessment, so their methods of routine monitoring are highly dependent on the energy of the neutron fields.Battelle has participated in neutron assessments at a number of LWR facilities to characterize neutron radiation fields and to evaluate the responses of plant dosimeters and survey instruments. In these studies, the tissue equivalent proportional counter was used for measuring neutron dose and dose equivalent rates, and multisphere spectrometers were used to measure energy distributions. The use of these instruments in LWR work locations is usually difficult because of extreme environmental conditions such as high temperatures.These studies have confirmed the presence of low-energy neutron fields in most work locations. The studies have also found that albedo dosimeters used at power plants typically overrespond significantly when using a calibration based on californium exposures. Survey instruments also respond highly in typical LWR environments.     

Residential exposures to pesticides and childhood leukaemia

Like many chemicals, carcinogenicity of pesticides is poorly characterised in humans, especially in children, so that the present knowledge about childhood leukaemia risk derives primarily from epidemiological studies. Overall, case-control studies published in the last decade have reported positive associations with home use of insecticides, mostly before the child's birth, while findings for herbicides are mixed. Previous studies relied solely on self-reports, therefore lacking information on active ingredients and effects of potential recall bias. Few series to date have examined the influence of children's genetic susceptibility related to transport and metabolism of pesticides. To overcome these limitations, investigators of the Northern California Childhood Leukaemia Study (NCCLS) have undertaken, in collaboration with a multidisciplinary team, a comprehensive assessment of residential pesticide exposure, including: (1) quality control of self-reports; (2) home pesticide inventory and linkage to the Environmental Protection Agency to obtain data on active ingredients; (3) collection and laboratory analyses of approximately 600 home dust samples for over 60 pesticides and (4) geographic information studies using California environmental databases to assess exposure to agricultural pesticides. The NCCLS is also conducting large-scale genotyping to evaluate the role of genes in xenobiotic pathways relevant to the transport and metabolism of pesticides. A better quantification of children's exposures to pesticides at home is critical to the evaluation of childhood leukaemia risk, especially for future gene-environment interaction studies.     

Health Canada's approach to manage risks to populations at risk during a radiological emergency

The approach that Health Canada uses to manage risks to individuals and to populations who might be exposed to ionising radiation is based upon the risk management paradigm. The paradigm differs little between an emergency and a non-emergency situations. In both events, technical experts assess the risk by determining the exposure to the source of radiation. They usually calculate the radiation dose and then assess the potential for any health effects. The initial technical assessments often use scoping calculations. The calculations for children recognise that they are smaller and have different metabolic rates and different behaviour from adults. However, most rigorous quantitative models for dosimetry do not differentiate between children and adults. The risk assessments that were conducted to evaluate the contamination of Canadians who were in London during the Litvenenko poisoning are a good example to illustrate this general approach. The scoping risk assessment concluded that the risks to children and adults were low. No Canadian children were exposed to polonium during this event and, to date, there have been no radiation emergencies in Canada where children have been exposed to a significant source of radiation. Therefore, the comparisons between theory and practice are very limited and conclusions are drawn from international experience and other incidents or sources of radiation exposure such as radon and medical exposures.     

Exposure to infections through day-care attendance and risk of childhood leukaemia

There is growing evidence supporting a role for infections in the aetiology of childhood leukaemia. Hypotheses proposed by both Greaves and Kinlen describe childhood leukaemia to be a rare response to one or more common infections acquired through personal contacts. Previous epidemiological studies have used day-care attendance as an indicator of the increased likelihood of early and frequent exposure to infections. It is well-documented that in developed countries, exposures to common infections occur more frequently in this type of setting. Within the Northern California Childhood Leukaemia Study, the role of social contact has been assessed and a unique 'child-hours' summary measure incorporating information on the number of months attending a day-care, mean hours per week at this day-care and the number of children in the day-care setting was constructed. In this review, the previously reported day-care results have been described, showing that in non-Hispanic White children, children in the highest category of total child-hours of exposure had a reduced risk of acute lymphoblastic leukaemia (ALL), particularly common B-cell precursor ALL (c-ALL), compared with children without such exposures, with evidence of a dose-response effect. In addition, a literature review of relevant studies has been conducted, examining the relationship between day-care attendance and risk of childhood ALL. Overall, the 14 studies identified provided consistent support for this hypothesis, with the majority of studies reporting some evidence of a reduced risk. A meta-analysis is currently underway, which will provide a quantitative evaluation of the overall consistency and strength of the association between day-care attendance or social contact and risk of childhood ALL.     

Human posture simulation to assess cumulative spinal load due to manual lifting. Part I: methods

The estimation of cumulative spinal load (CSL) resulting from exposure to manual materials handling (MMH) may provide a sensitive method for assessing the risk of highly varying exposures. This article reports on a CSL method that involves human posture simulation of workers from videotape in order to assess spinal load exposures due to MMH. The proposed method appears to be sensitive to different durations of exposure, easy to use and useful for assessing jobs with a high degree of variability in task characteristics between lifts. Although the method remains to be validated, it appears to be a useful addition to the range of tools available for assessing manual lifting exposures in worksite-based epidemiologic studies. Ergonomic methods are lacking for assessing highly variable MMH tasks, such as tasks found in warehousing. The existing methods do not include sufficient factors to account for variable exposure patterns or tasks with highly variable task characteristics, such as varying load weights and lift geometries. The CSL assessment method described in this article may provide a way to evaluate these types of tasks in order to assess the overall risk of workers developing work-related musculoskeletal disorders.     

Circadian neuroendocrine physiology and electromagnetic field studies: precautions and complexities

The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis'. has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock.     

Do electromagnetic fields enhance the effects of environmental carcinogens?

Epidemiological studies have reported an increased risk of leukaemia in children who are exposed to extremely low-frequency (ELF) magnetic fields (MF), suggesting that ELF MFs may be carcinogenic to humans. No carcinogenic effects have been found in animal studies that have tested ELF MFs alone. Similarly, genotoxicity studies have generally not shown effects from MFs alone. However, ELF MFs have been reported to enhance the effects of known carcinogenic or mutagenic agents in a few animal studies and in several in vitro studies. This paper discusses the findings of studies on such combined effects. The majority of in vitro studies have reported positive findings, which supports the conclusion that MFs of 100 microT or higher interact with other chemical and physical agents. Further studies should address biophysical mechanisms and dose-response relationship below 100 microT. Animal studies designed according to the classical initiation-promotion concept may not be sufficient for studying the cocarcinogenic effects of MFs, and further studies using novel study designs would be useful. Epidemiological data on the interaction between MFs and other environmental agents are scant and inconclusive, and any further studies may be difficult because of the scarcity of subjects with suitable combined exposures.