Motor neuron disease risk and magnetic field exposures.

BACKGROUND: Many studies have investigated magnetic field exposure and the risks of motor neuron disease (MND). Meta-analyses have found positive associations but a causal relationship has not been established. AIMS: To investigate the risks of MND and occupational exposure to magnetic fields in a large UK cohort. METHODS: Mortality of 37 986 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1987-2018. Employees were first employed in the period 1942-82 and were still in employment on the 1 November, 1987. Detailed calculations enabled estimates to be made of magnetic field exposures. Observed deaths were compared with expected numbers based on mortality rates for the general population of England and Wales and Poisson regression was used to calculate rate ratios (relative risks) for categories of lifetime, lagged (distant) and lugged (recent) magnetic field exposure. RESULTS: Mortality from MND in the total cohort was similar to national rates (observed 69, expected 71.3, SMR 97, 95% CI 76-122). There were no statistically significant trends of risks increasing with lifetime, recent or distant magnetic field exposure, although positive associations were observed for some categories of recent exposure. CONCLUSIONS: The study did not find that the cohort had elevated risks of MND as a consequence of occupational lifetime exposure to magnetic fields, although a possible role for recent exposures could usefully be investigated in other datasets.

Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.

BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted. OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths. METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries. RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use. CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.

Radiofrequency Exposure Amongst Employees of Mobile Network Operators and Broadcasters.

Little is known about personal exposure to radiofrequency (RF) fields amongst employees in the telecommunications industry responsible for installing and maintaining transmitters. IARC classified RF exposure as a possible carcinogen, although evidence from occupational studies was judged to be inadequate. Hence, there is a need for improved evidence of any potentially adverse health effects amongst the workforce occupationally exposed to RF radiation. In this study, results are presented from an exposure survey using data from personal monitors used by employees in the broadcasting and telecommunication industries of the UK. These data were supplemented by spot measurements using broadband survey metres and information on daily work activities provided by employee questionnaires. The sets of real-time personal data were categorised by four types of site determined by the highest powered antenna present (high, medium or low power and ground-level sites). For measurements gathered at each type of site, the root mean square and a series of box plots were produced. Results from the daily activities diaries suggested that riggers working for radio and television broadcasters were exposed to much longer periods as compared to colleagues working for mobile operators. Combining the results from the measurements and daily activity diaries clearly demonstrate that exposures were highest for riggers working for broadcasting sites. This study demonstrates that it is feasible to carry out exposure surveys within these populations that will provide reliable estimates of exposure that can be used for epidemiological studies of occupational groups exposed to RF fields.

Visualising and Thinking and Interpreting. Response to the Burstyn and De Roos Comments on Sorahan, T. Multiple Myeloma and Glyphosate Use: A Re-Analysis of US Agricultural Health Study (AHS) Data. Int. J. Environ. Res. Public Health 2015, 12, 1548-1559.

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A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

Glyphosate epidemiology expert panel review: a weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin's lymphoma or multiple myeloma.

We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) - two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case-control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM.

Incidence of Myelodysplastic Syndrome in UK Petroleum Distribution and Oil Refinery Workers, 1995-2011.

The incidence of myelodysplastic syndrome (MDS) experienced by cohorts of 16,467 petroleum distribution workers and 28,554 oil refinery workers has been investigated. Study subjects were all those male employees first employed at one of 476 UK petroleum distribution centres or eight UK oil refineries in the period 1946-1974; all subjects had a minimum of twelve months employment with some employment after 1st January, 1951. Observed numbers (Obs) of MDS cases were compared with expectations based on national incidence rates for the period 1995-2011. The overall standardised registration ratio (SRR) was 73 (Obs = 17) in petroleum distribution workers for the age-range 15-84 years, and 77 (Obs = 21) for the age-range 15-99 years. The overall SRR was 81 (Obs = 29) in oil refinery workers for the age-range 15-84 years, and 83 (Obs = 36) for the age-range 15-99 years. More detailed analyses were carried out in terms of year of registration, period from hire, decade of hire, and duration of employment. The overall SRR findings did not provide clear evidence for the presence of an occupational cancer hazard, and provide no support for the hypothesis that low-level benzene exposure has an important effect on the risks of MDS.

Meta-Analysis of Cardiac Mortality in Three Cohorts of Carbon Black Production Workers.

Epidemiological studies have demonstrated associations between airborne environmental particle exposure and cardiac disease and mortality; however, few have examined such effects from poorly soluble particles of low toxicity such as manufactured carbon black (CB) particles in the work place. We combined standardised mortality ratio (SMR) and Cox proportional hazards results from cohort studies of US, UK and German CB production workers. Under a common protocol, we analysed mortality from all causes, heart disease (HD), ischemic heart disease (IHD) and acute myocardial infarction (AMI). Fixed and random effects (RE) meta-regression models were fit for employment duration, and for overall cumulative and lugged quantitative CB exposure estimates. Full cohort meta-SMRs (RE) were 1.01 (95% confidence interval (CI) 0.79-1.29) for HD; 1.02 (95% CI 0.80-1.30) for IHD, and 1.08 (95% CI 0.74-1.59) for AMI mortality. For all three outcomes, meta-SMRs were heterogeneous, increased with time since first and time since last exposure, and peaked after 25-29 or 10-14 years, respectively. Meta-Cox coefficients showed no association with lugged duration of exposure. A small but imprecise increased AMI mortality risk was suggested for cumulative exposure (RE-hazards ratio (HR) = 1.10 per 100 mg/m³-years; 95% CI 0.92-1.31), but not for lugged exposures. Our results do not demonstrate that airborne CB exposure increases all-cause or cardiac disease mortality.

Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study (AHS) data.

A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993-2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use.

Lung cancer risk and solid fuel smoke exposure: a systematic review and meta-analysis.

The aim of this systematic review was to quantify the impact of biomass fuel and coal use on lung cancer and to explore reasons for heterogeneity in the reported effect sizes. A systematic review of primary studies reporting the relationship between solid fuel use and lung cancer was carried out, based on pre-defined criteria. Studies that dealt with confounding factors were used in the meta-analysis. Fuel types, smoking, country, cancer cell type and sex were considered in sub-group analyses. Publication bias and heterogeneity were estimated. The pooled effect estimate for coal smoke as a lung carcinogen (OR 1.82, 95% CI 1.60-2.06) was greater than that from biomass smoke (OR 1.50, 95% CI 1.17-1.94). The risk of lung cancer from solid fuel use was greater in females (OR 1.81, 95% CI 1.54-2.12) compared to males (OR 1.16, 95% CI 0.79-1.69). The pooled effect estimates were 2.33 (95% CI 1.72-3.17) for adenocarcinoma, 3.58 (1.58-8.12) for squamous cell carcinoma and 1.57 (1.38-1.80) for tumours of unspecified cell type. These findings suggest that in-home burning of both coal and biomass is consistently associated with an increased risk of lung cancer.

Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008.

OBJECTIVE: To carry out a descriptive analysis of mesothelioma deaths reported worldwide between 1994 and 2008. METHODS: We extracted data on mesothelioma deaths reported to the World Health Organization mortality database since 1994, when the disease was first recorded. We also sought information from other English-language sources. Crude and age-adjusted mortality rates were calculated and mortality trends were assessed from the annual percentage change in the age-adjusted mortality rate. FINDINGS: In total, 92,253 mesothelioma deaths were reported by 83 countries. Crude and age-adjusted mortality rates were 6.2 and 4.9 per million population, respectively. The age-adjusted mortality rate increased by 5.37% per year and consequently more than doubled during the study period. The mean age at death was 70 years and the male-to-female ratio was 3.6:1. The disease distribution by anatomical site was: pleura, 41.3%; peritoneum, 4.5%; pericardium, 0.3%; and unspecified sites, 43.1%. The geographical distribution of deaths was skewed towards high-income countries: the United States of America reported the highest number, while over 50% of all deaths occurred in Europe. In contrast, less than 12% occurred in middle- and low-income countries. The overall trend in the age-adjusted mortality rate was increasing in Europe and Japan but decreasing in the United States. CONCLUSION: The number of mesothelioma deaths reported and the number of countries reporting deaths increased during the study period, probably due to better disease recognition and an increase in incidence. The different time trends observed between countries may be an early indication that the disease burden is slowly shifting towards those that have used asbestos more recently.

Global magnitude of reported and unreported mesothelioma.

BACKGROUND: Little is known about the global magnitude of mesothelioma. In particular, many developing countries, including some with extensive historical use of asbestos, do not report mesothelioma. OBJECTIVES: We estimated the global magnitude of mesothelioma accounting for reported and unreported cases. METHODS: For all countries with available data on mesothelioma frequency and asbestos use (n=56), we calculated the 15-year cumulative number of mesotheliomas during 1994-2008 from data available for fewer years and assessed its relationship with levels of cumulative asbestos use during 1920-1970. We used this relationship to predict the number of unreported mesotheliomas in countries for which no information on mesothelioma is available but which have recorded asbestos use (n=33). RESULTS: Within the group of 56 countries with data on mesothelioma occurrence and asbestos use, the 15-year cumulative number of mesothelioma was approximately 174,300. There was a statistically significant positive linear relation between the log-transformed national cumulative mesothelioma numbers and the log-transformed cumulative asbestos use (adjusted R(2)=0.83, p<0.0001). Extrapolated to the group of 33 countries without reported mesothelioma, a total of approximately 38,900 (95% confidence interval, 36,700-41,100) mesothelioma cases were estimated to have occurred in the 15-year period (1994-2008). CONCLUSIONS: We estimate conservatively that, globally, one mesothelioma case has been overlooked for every four to five reported cases. Because our estimation is based on asbestos use until 1970, the many countries that increased asbestos use since then should anticipate a higher disease burden in the immediate decades ahead.

Research recommendations for selected IARC-classified agents.

OBJECTIVES: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

Cancer risk among Japanese chromium platers, 1976-2003.

OBJECTIVE: The aim of our prospective cohort study was to assess cancer mortality risks among chromium platers. METHODS: The cohort comprised 1193 male platers (626 with exposure to chromium, the remainder with no exposure) with a follow-up period of 27 years (1 October 1976 to 31 December 2003). Mortality risk was assessed by the standardized mortality rate (SMR) with reference to the national population. RESULTS: Lung cancer mortality was elevated only in the chromium plater subgroup, with borderline statistical significance [SMR=1.46, observations (Obs)=28, 95% confidence interval (95% CI) 0.98-2.04]. The chromium plater subgroup also showed elevated mortality risks for brain tumor (SMR=9.14, Obs=3, 95% CI 1.81-22.09) and malignant lymphoma (SMR=2.84, Obs=6, 95% CI 1.05-5.51). Risks were particularly elevated for lung cancer (SMR=1.59, Obs=23, 95% CI 1.01-2.38) and malignant lymphoma (SMR=3.80, Obs=6, 95% CI 1.39-8.29) among those with initial chromium exposure prior to 1970. CONCLUSIONS: In Japan, occupational exposure to chromium through work as a chromium plater is a risk factor for lung cancer, especially for platers working prior to 1970. Occupational chromium exposure may also increase the risk of brain tumor and malignant lymphoma.