What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study.

BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF, MUC5B rs35705950, is unknown. METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs35705950 was investigated using a genetic dominant model. RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs35705950. CONCLUSION: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of MUC5B rs35705950. TRIAL REGISTRATION NUMBER: NCT03211507.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin's lymphoma and Parkinson's disease: results of three meta-analyses.

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers' imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin's lymphoma (NHL) (29 articles) and Parkinson's disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case-control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

Lifetime cumulative exposure to rubber dust, fumes and N-nitrosamines and non-cancer mortality: a 49-year follow-up of UK rubber factory workers.

OBJECTIVES: To examine associations between occupational exposures to rubber dust, rubber fumes and N-nitrosamines and non-cancer mortality. METHODS: A cohort of 36 441 males aged 35+ years employed in British rubber factories was followed-up to 2015 (94% deceased). Competing risk survival analysis was used to assess risks of dying from non-cancer diseases (respiratory, urinary, cerebrovascular, circulatory and digestive diseases). Occupational exposures to rubber dust, rubber fumes, N-nitrosamines were derived based on a population-specific quantitative job-exposure matrix which in-turn was based on measurements in the EU-EXASRUB database. RESULTS: Exposure-response associations of increased risk with increasing exposure were found for N-nitrosomorpholine with mortality from circulatory diseases (subdistribution hazard ratio (SHR) 1.17; 95% CI 1.12 to 1.23), ischaemic heart disease (IHD) (SHR 1.19; 95% CI 1.13 to 1.26), cerebrovascular disease (SHR 1.19; 95% CI 1.07 to 1.32) and exposures to N-nitrosodimethylamine with respiratory disease mortality (SHR 1.41; 95% CI 1.30 to 1.53). Increased risks for mortality from circulatory disease, IHD and digestive diseases were found with higher levels of exposures to rubber dust, rubber fumes and N-nitrosamines sum, without an exposure-dependent manner. No associations were observed between rubber dust, rubber fumes and N-nitrosamines exposures with mortality from asthma, urinary disease, bronchitis, emphysema, liver disease and some digestive diseases. CONCLUSIONS: In a cohort of rubber factory workers with 49 years of follow-up, increased risk for mortality from circulatory, cerebrovascular, respiratory and digestive diseases were found to be associated with cumulative occupational exposures to specific agents.

Systematic review of methods used to assess exposure to pesticides in occupational epidemiology studies, 1993-2017.

OBJECTIVE: Numerous exposure assessment methods (EAM) exist for investigating health effects of occupational exposure to pesticides. Direct (eg, biomonitoring) and indirect methods (eg, self-reported exposures) are however associated with degrees of exposure misclassification. We systematically reviewed EAM in studies of occupational pesticide exposure. METHODS: We searched for articles reporting observational epidemiological studies in MEDLINE and Embase published 1993 to 2017. The relative frequency of EAM was analysed according to EAM type (direct and indirect methods), health outcome, study design, study location (country) and specificity of assessment. Temporal trends in EAM were analysed. RESULTS: In 1298 included articles 1521 EAM occurrences were documented. Indirect EAM (78.3%), primarily self-reported exposures (39.3%) and job titles assessments (9.5%), were mainly applied in case-control studies (95.0%), in high-income countries (85.0%) and in studies of doctor-diagnosed health outcomes (>85%). Direct EAM (20.8%), primarily biomonitoring of blood (15.6%) or urine (4.7%), were predominantly applied in cross-sectional studies (29.8%), in lower middle-income countries (40.9%) and in studies of neurological (50.0%) outcomes. Between 1993 to 2017 no distinct time trends regarding the ratio indirect to direct methods was seen. Within the category of indirect methods use of self-reported exposures and job exposure matrices increased while assessments by job titles and registers decreased. The use of algorithms showed no trend. The specificity of pesticide assessment increased since studies assessing exposure by using job title as a proxy declined. Assessments of type of pesticide increased. CONCLUSION: Over the last 25 years, the ratio (5:1) of indirect to direct EAM applied in articles on occupational pesticide epidemiology stayed relatively constant; changes were mainly attributable to increasing use of self-reported exposures and job exposure matrices. This review, combined with studies assessing EAM validity, will inform on magnitudes of exposure misclassification and help improve the quality of studies on occupational pesticides exposure.

Job-exposure matrix for historical exposures to rubber dust, rubber fumes and n-Nitrosamines in the British rubber industry.

OBJECTIVES: To develop a quantitative historical job-exposure matrix (JEM) for rubber dust, rubber fumes and n-Nitrosamines in the British rubber industry for 1915-2002 to estimate lifetime cumulative exposure (LCE) for a cohort of workers with 49 years follow-up. METHODS: Data from the EU-EXASRUB database-rubber dust (n=4157), rubber fumes (n=3803) and n-Nitrosamines (n=10 115) collected between 1977 and 2002-were modelled using linear mixed-effects models. Sample year, stationary/personal measurement, industry sector and measurement source were included as fixed explanatory variables and factory as random intercept. Model estimates and extrapolations were used to construct a JEM covering all departments in both sectors of the rubber manufacturing industries for the years 1915-2002. JEM-estimates were linked to all cohort members to calculate LCE. Sensitivity analyses related to assumptions about extrapolation of time trends were also conducted. RESULTS: Changes in rubber dust exposures ranged from -6.3 %/year (crude materials/mixing) to -1.0 %/year (curing) and -6.5 %/year (crude materials/mixing) to +0.5 %/year (finishing, assembly and miscellaneous) for rubber fumes. Declines in n-Nitrosamines ranged from -17.9 %/year (curing) to -1.3 %/year (crude materials and mixing). Mean LCEs were 61 mg/m3-years (rubber dust), 15.6 mg/ m3-years (rubber fumes), 2483.2 µg/m3-years (n-Nitrosamines sum score), 18.6 µg/m3-years (N-nitrosodimethylamine) and 15.0 µg/m3-years (N-itrosomorpholine). CONCLUSIONS: All exposures declined over time. Greatest declines in rubber dust and fumes were found in crude materials and mixing and for n-Nitrosamines in curing/vulcanising and preprocessing. This JEM and estimated LCEs will allow for evaluation of exposure-specific excess cancer risks in the British rubber industry.

Lifetime exposure to rubber dusts, fumes and N-nitrosamines and cancer mortality in a cohort of British rubber workers with 49 years follow-up.

OBJECTIVES: To quantitatively evaluate exposure-response associations between occupational exposures to rubber dust, fumes and N-nitrosamines and cancer mortality in the UK rubber industry. METHODS: Competing risk survival analyses were used to examine cancer mortality risk in a cohort of 36 441 males aged 35+ years employed in the British rubber industry in 1967, followed up to 2015 (94% mortality). Exposure measurements are based on a population-specific quantitative job-exposure matrix for rubber dust, rubber fumes and N-nitrosamines from the EU-EXASRUB project. RESULTS: Exposure (lifetime cumulative (LCE))-response associations were found for N-nitrosomorphiline and all cancers (subdistribution HR (SHR) 1.48, 95% CI 1.39 to 1.57) and cancers of the bladder, stomach, multiple myeloma, oesophagus, prostate and pancreas, as well as for N-nitrosodimethylamine and all cancers (SHR 2.08, 95% CI 1.96 to 2.21) and cancers of the bladder, stomach, leukaemia, multiple myeloma, prostate and liver. LCE to the N-nitrosamines sum were associated with increased risks from all cancers (SHR 1.89, 95% CI 1.78 to 2.01) and cancers of the lung, non-Hodgkin's lymphoma and brain. LCE to rubber dust and fumes are associated with increased mortality from all cancers (rubber dust SHR 1.67, 95% CI 1.58 to 1.78; rubber fumes SHR 1.91, 95% CI 1.80 to 2.03) and cancers of the bladder, lung, stomach, leukaemia, multiple myeloma, non-Hodgkin's lymphoma, oesophagus, prostate, pancreas and liver. CONCLUSIONS: Consistent with previous studies, N-nitrosamines exposures are associated with mortality from cancers of the bladder, lung, stomach, leukaemia, multiple myeloma, oesophagus, prostate, pancreas and liver. The long follow-up with nearly complete mortality enabled estimations of lifetime cancer mortality risk from occupational exposures in the rubber industry.

Assessing progress in protecting non-smokers from secondhand smoke.

OBJECTIVE: To examine trends in population exposure to secondhand smoke (SHS) and consider two exposure metrics as appropriate targets for tobacco control policy-makers. DESIGN: Comparison of adult non-smokers' salivary cotinine data available from 11 Scottish Health Surveys between 1998 and 2016. METHODS: The proportions of non-smoking adults who had measurable levels of cotinine in their saliva were calculated for the 11 time points. The geometric mean (GM) concentrations of cotinine levels were calculated using Tobit regression. Changes in both parameters were assessed for the whole period and also for the years since implementation of smoke-free legislation in Scotland in 2006. RESULTS: Salivary cotinine expressed as a GM fell from 0.464 ng/mL (95% CI 0.444 to 0.486 ng/mL) in 1998 to 0.013 ng/mL (95% CI 0.009 to 0.020 ng/mL) in 2016: a reduction of 97.2%. The percentage of non-smoking adults who had no measurable cotinine in their saliva increased by nearly sixfold between 1998 (12.5%, 95% CI 11.5% to 13.6%) and 2016 (81.6%, 95% CI 78.6% to 84.6%). Reductions in population exposure to SHS have continued even after smoke-free legislation in 2006. CONCLUSIONS: Scotland has witnessed a dramatic reduction in SHS exposure in the past two decades, but there are still nearly one in five non-smoking adults who have measurable exposure to SHS on any given day. Tobacco control strategies globally should consider the use of both the proportion of non-smoking adults with undetectable salivary cotinine and the GM as targets to encourage policies that achieve a smoke-free future.

Comparison of methods for converting Dylos particle number concentrations to PM2.5 mass concentrations.

The aim of this study was to (a) develop a method for converting particle number concentrations (PNC) obtained by Dylos to PM2.5 mass concentrations, (b) compare this conversion with similar methods available in the literature, and (c) compare Dylos PM2.5 obtained using all available conversion methods with gravimetric samples. Data were collected in multiple residences in three European countries using the Dylos and an Aerodynamic Particle Sizer (APS, TSI) in the Netherlands or an optical particle counter (OPC, GRIMM) in Greece. Two statistical fitted curves were developed based on Dylos PNC and either an APS or an OPC particle mass concentrations (PMC). In addition, at the homes of 16 volunteers (UK and Netherlands), Dylos measurements were collected along with gravimetric samples. The Dylos PNC were transformed to PMC using all the fitted curves obtained during this study (and three found in the literature) and were compared with gravimetric samples. The method developed in the present study using an OPC showed the highest correlation (Pearson (R) = 0.63, Concordance (ρc ) = 0.61) with gravimetric data. The other methods resulted in an underestimation of PMC compared to gravimetric measurements (R = 0.65-0.55, ρc  = 0.51-0.24). In conclusion, estimation of PM2.5 concentrations using the Dylos is acceptable for indicative purposes.

Effectiveness of face masks used to protect Beijing residents against particulate air pollution.

OBJECTIVES: Many residents in Beijing use disposable face masks in an attempt to protect their health from high particulate matter (PM) concentrations. Retail masks may be certified to local or international standards, but their real-life performance may not confer the exposure reduction potential that is marketed. This study aimed to evaluate the effectiveness of a range of face masks that are commercially available in China. METHODS: Nine masks claiming protection against fine PM (PM2.5) were purchased from consumer outlets in Beijing. The masks' filtration efficiency was tested by drawing airborne diesel exhaust through a section of the material and measuring the PM2.5 and black carbon (BC) concentrations upstream and downstream of the filtering medium. Four masks were selected for testing on volunteers. Volunteers were exposed to diesel exhaust inside an experimental chamber while performing sedentary tasks and active tasks. BC concentrations were continuously monitored inside and outside the mask. RESULTS: The mean per cent penetration for each mask material ranged from 0.26% to 29%, depending on the flow rate and mask material. In the volunteer tests, the average total inward leakage (TIL) of BC ranged from 3% to 68% in the sedentary tests and from 7% to 66% in the active tests. Only one mask type tested showed an average TIL of less than 10%, under both test conditions. CONCLUSIONS: Many commercially available face masks may not provide adequate protection, primarily due to poor facial fit. Our results indicate that further attention should be given to mask design and providing evidence-based guidance to consumers.

British rubber and cable industry cohort: 49-year mortality follow-up.

BACKGROUND: The International Agency for Research on Cancer (IARC) has determined there is sufficient evidence that working in the rubber manufacturing industry increases the risk of cancers of the stomach, lung, bladder and leukaemia and lymphoma. OBJECTIVES: To examine mortality patterns of a prospective cohort of men from the rubber and cable manufacturing industries in Great Britain. METHODS: SMRs were calculated for males aged 35+ years at start of follow-up in 1967-2015 using the population of England and Wales as the external comparator. Tests for homogeneity and trends in SMRs were also completed. RESULTS: For all causes, all malignant neoplasms, non-malignant respiratory diseases and circulatory diseases, SMRs were significantly elevated, and also particularly for cancers of the stomach (SMR=1.26,95% CI 1.18 to 1.36), lung (1.25,95% CI 1.21 to 1.29) and bladder (1.16,95% CI 1.05 to 1.28). However, the observed deaths for leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma were as expected. Bladder cancer risks were elevated only in workers exposed to antioxidants containing 1-naphthylamine and 2-naphthylamine. CONCLUSIONS: This study provides evidence of excess risks in the rubber industry for some non-cancer diseases and supports IARC's conclusions in relation to risks for cancers of the bladder, lung and stomach, but not for leukaemia, NHL or multiple myeloma.

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers: study protocol.

BACKGROUND: Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. METHOD/DESIGN: Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level - i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April-September) using body-mounted UV sensors. DISCUSSION: This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. TRIAL REGISTRATION: ISRCTN15888934 retrospectively registered 15.01.2018.

The Essential Elements of a Risk Governance Framework for Current and Future Nanotechnologies.

Societies worldwide are investing considerable resources into the safe development and use of nanomaterials. Although each of these protective efforts is crucial for governing the risks of nanomaterials, they are insufficient in isolation. What is missing is a more integrative governance approach that goes beyond legislation. Development of this approach must be evidence based and involve key stakeholders to ensure acceptance by end users. The challenge is to develop a framework that coordinates the variety of actors involved in nanotechnology and civil society to facilitate consideration of the complex issues that occur in this rapidly evolving research and development area. Here, we propose three sets of essential elements required to generate an effective risk governance framework for nanomaterials. (1) Advanced tools to facilitate risk-based decision making, including an assessment of the needs of users regarding risk assessment, mitigation, and transfer. (2) An integrated model of predicted human behavior and decision making concerning nanomaterial risks. (3) Legal and other (nano-specific and general) regulatory requirements to ensure compliance and to stimulate proactive approaches to safety. The implementation of such an approach should facilitate and motivate good practice for the various stakeholders to allow the safe and sustainable future development of nanotechnology.

Mortality of a cohort of workers in Great Britain with blood lead measurements.

OBJECTIVES: We examined the mortality of a historic cohort of workers in Great Britain with measured blood lead levels (BLLs). METHODS: SMRs were calculated with the population of Great Britain as the external comparator. Trends in mortality with mean and maximum BLLs and assessed lead exposure were examined using Cox regression. RESULTS: Mean follow-up length among the 9122 study participants was 29.2 years and 3466 deaths occurred. For all causes and all malignant neoplasms, the SMRs were statistically significantly raised. For disease groups of a priori interest, the SMR was significantly raised for lung cancer but not for stomach, brain, kidney, bladder or oesophageal cancers. The SMR was not increased for non-malignant kidney disease but was borderline significantly increased for circulatory diseases, for ischaemic heart disease (IHD) and cerebrovascular disease (CVD). No significant trends with exposure were observed for the cancers of interest, but for circulatory diseases and IHD, there was a statistically significant trend for increasing HR with mean and maximum BLLs. CONCLUSIONS: This study found an excess of lung cancer, although the risk was not clearly associated with increasing BLLs. It also found marginally significant excesses of IHD and CVD, the former being related to mean and maximum BLLs. The finding for IHD may have been due to lead, but could also have been due to other dust exposure associated with lead exposure and possibly tobacco smoking. Further work is required to clarify this and the carcinogenicity of lead.

Fine particulate matter concentrations in smoking households: just how much secondhand smoke do you breathe in if you live with a smoker who smokes indoors?

OBJECTIVE: Using data on fine particulate matter less than 2.5 µm (PM2.5) concentrations in smoking and non-smoking homes in Scotland to estimate the mass of PM2.5 inhaled by different age groups. METHODS: Data from four linked studies, with real-time measurements of PM2.5 in homes, were combined with data on typical breathing rates and time-activity patterns. Monte Carlo modelling was used to estimate daily PM2.5 intake, the percentage of total PM2.5 inhaled within the home environment and the percentage reduction in daily intake that could be achieved by switching to a smoke-free home. RESULTS: Median (IQR) PM2.5 concentrations from 93 smoking homes were 31 (10-111) µg/m(3) and 3 (2-6.5) µg/m(3) for the 17 non-smoking homes. Non-smokers living with smokers typically have average PM2.5 exposure levels more than three times higher than the WHO guidance for annual exposure to PM2.5 (10 µg/m(3)). CONCLUSIONS: Fine particulate pollution in Scottish homes where smoking is permitted is approximately 10 times higher than in non-smoking homes. Taken over a lifetime many non-smokers living with a smoker inhale a similar mass of PM2.5 as a non-smoker living in a heavily polluted city such as Beijing. Most non-smokers living in smoking households would experience reductions of over 70% in their daily inhaled PM2.5 intake if their home became smoke-free. The reduction is likely to be greatest for the very young and for older members of the population because they typically spend more time at home.

Comparison of residents' pesticide exposure with predictions obtained using the UK regulatory exposure assessment approach.

The UK regulatory methods currently used for estimating residents' potential pesticide exposure were assessed to determine whether they provide sufficiently conservative estimates. A non-random sample of 149 residents living within 100 m of fields where pesticides were sprayed provided first morning void urine samples one and/or two days after spraying. Using farmers' spray information, regulatory exposure assessment (REA) models were applied to estimate potential pesticide intake among residents, with a toxicokinetic (TK) model used to estimate urinary biomarker concentrations in the mornings of the two days following the spray. These were compared with actual measured urinary biomarker concentrations obtained following the spray applications. The study focused on five pesticides (cypermethrin, penconazole, captan, chlorpyrifos and chlormequat). All measured cypermethrin urinary biomarker levels were lower than the REA-predicted concentrations. Over 98% and 97% of the measured urinary biomarker concentrations for penconazole and captan respectively were lower than the REA-predicted exposures. Although a number of the chlorpyrifos and chlormequat spray-related urinary biomarker concentrations were greater than the predictions, investigation of the background urinary biomarker concentrations suggests these were not significantly different from the levels expected had no pesticide spraying occurred. The majority of measured concentrations being well below the REA-predicted concentrations indicate that, in these cases, the REA is sufficiently conservative.