Factors influencing occupational exposure to pyrethroids and glyphosate: An analysis of urinary biomarkers in Malaysia, Uganda and the United Kingdom.

BACKGROUND: Long-term exposure to pesticides is often assessed using semi-quantitative models. To improve these models, a better understanding of how occupational factors determine exposure (e.g., as estimated by biomonitoring) would be valuable. METHODS: Urine samples were collected from pesticide applicators in Malaysia, Uganda, and the UK during mixing/application days (and also during non-application days in Uganda). Samples were collected pre- and post-activity on the same day and analysed for biomarkers of active ingredients (AIs), including synthetic pyrethroids (via the metabolite 3-phenoxybenzoic acid [3-PBA]) and glyphosate, as well as creatinine. We performed multilevel Tobit regression models for each study to assess the relationship between exposure modifying factors (e.g., mixing/application of AI, duration of activity, personal protective equipment [PPE]) and urinary biomarkers of exposure. RESULTS: From the Malaysia, Uganda, and UK studies, 81, 84, and 106 study participants provided 162, 384 and 212 urine samples, respectively. Pyrethroid use on the sampling day was most common in Malaysia (n = 38; 47%), and glyphosate use was most prevalent in the UK (n = 93; 88%). Median pre- and post-activity 3-PBA concentrations were similar, with higher median concentrations post-compared to pre-activity for glyphosate samples in the UK (1.7 to 0.5 µg/L) and Uganda (7.6 to 0.8 µg/L) (glyphosate was not used in the Malaysia study). There was evidence from individual studies that higher urinary biomarker concentrations were associated with mixing/application of the AI on the day of urine sampling, longer duration of mixing/application, lower PPE protection, and less education/literacy, but no factor was consistently associated with exposure across biomarkers in the three studies. CONCLUSIONS: Our results suggest a need for AI-specific interpretation of exposure modifying factors as the relevance of exposure routes, levels of detection, and farming systems/practices may be very context and AI-specific.

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.

Asthma in pesticide users: an update from the Great Britain Prospective Investigation of Pesticide Applicators' Health (PIPAH) cohort study.

OBJECTIVES: To define the prevalence and incidence of asthma in a large working population of pesticide workers and to assess which exposures are potentially of relevance to causing or aggravating this condition. METHODS: A baseline cross-sectional study at recruitment (2013-2017, n=5817), with follow-up in 2018 (n=2578), was carried out in predominantly Great Britain based pesticide workers. At baseline, participants completed a health and work questionnaire which included questions on demographic, lifestyle, socioeconomic and work-related factors, pesticide use and doctor diagnosed health conditions. In January 2018, a follow-up questionnaire focused on respiratory ill health, with questions covering self-reported respiratory symptoms and doctor diagnosed respiratory conditions. The associations of various exposures with asthma were estimated using logistic regression adjusting for age as a continuous variable, and for sex where possible. An estimate of hours worked with pesticides in the previous year was calculated for each participant. RESULTS: At baseline, 608 (10.4%) had doctor diagnosed asthma. In 2018 the figure was 297 (11.5% of the follow-up population); the incidence of new asthma cases between surveys was 1.7 cases per 1000 participants per year. At follow-up, 18.1% reported wheeze in the last 12 months, 73.2% of those with self-reported asthma noted it to be persistent and using a more specific definition of asthma (doctor diagnosed asthma with at least one asthma-related symptom in the last year); 6.8% (95% CI 5.9% to 7.9%) fulfilled this definition. At follow-up, 127 participants felt that their asthma was caused or made worse by their work, with 77 (63.6%) nominating organic dust, 13 (10.7%) unspecified dust, 12 (9.9%) chemicals, 9 (7.4%) mixed exposures, 7 (5.8%) physical agents and 3 (2.5%) fumes or other irritants. There was little or no association between high pesticide exposure and doctor diagnosed asthma or self-reported recent wheeze, although there was an elevated risk for work-related wheeze (OR for high exposure=2.67; 95% CI 1.16 to 6.18). High pesticide exposure (high vs low exposure category OR 2.68, 95% CI 1.28 to 5.60) was also associated with work-related chest tightness. Exposure to organic dusts was associated (significantly, p=0.026) with persistent asthma when adjusted for the effects of age and smoking. CONCLUSIONS: This large study of pesticide workers has identified expected levels of doctor diagnosed asthma, and high levels of self-reported respiratory symptoms. Pesticide exposure was associated with an increased risk of self-reported work-related wheeze, but not with asthma or wheeze in general. Further work is needed to identify more clearly which exposures within a complex mixed exposure profile are likely causative in order to best focus interventions to reduce work-related asthma and related conditions.

Recall of exposure in UK farmers and pesticide applicators: trends with follow-up time.

BACKGROUND: Occupational epidemiological studies on pesticide use commonly rely on self-reported questionnaire or interview data to assess exposure. Insight into recall accuracy is important, as misclassification of exposures due to imperfect recall can bias risk estimates. METHODS: We assessed the ability of workers in three UK cohorts (Prospective Investigation of Pesticide Applicators' Health [PIPAH], Pesticide Users' Health Study [PUHS], and Study of Health in Agricultural Work [SHAW]) to remember their working history related to pesticide exposure over time periods ranging from 3 to 14 years prior. During 2019-2020, cohort participants were re-surveyed using a similar questionnaire to that used previously. We compared recall of responses at follow-up to those reported at baseline related to crops/areas of work, use of personal protective equipment (PPE) items, hygiene habits, frequency of pesticide use, and application method. To assess the extent of recall, we used sensitivity, specificity, the percentage of overall agreement, and area under the curve (AUC) values. We also examined the presence of over or underestimation of recalled years, and days and hours per year, of working with pesticides using geometric mean ratios (GMR) and regression analysis to investigate any trends based on demographic characteristics. RESULTS: There were 643 individuals who completed both the baseline and follow-up surveys in the three cohorts with response rates ranging from 17 to 46%. There was a strong correlation (rho = 0.77) between the baseline and recalled years working with pesticides, though higher values were reported at follow-up (GMR = 1.18 [95% confidence interval: 1.07-1.30]) with no consistent differences by demographic characteristics. There was stronger agreement in the recalled days compared to hours per year in two of the cohorts. Recall for a number of exposure determinants across short and longer periods entailed overall agreement of >70%, though with some differences: for example, sensitivity for long-term recall of crops was poor (<43% in PUHS), whereas short-term recall of hygiene practices was good (AUC range = 0.65-1.00 in PIPAH). CONCLUSION: Results indicate that recall ability may deteriorate over a longer period. Although low-response rates may require these findings to be interpreted with caution, recall for a number of exposure determinants appeared reliable, such as crops and hygiene practices within 3 years, as well as days per year working with pesticides.

Evaluation of two-year recall of self-reported pesticide exposure among Ugandan smallholder farmers.

OBJECTIVES: To evaluate smallholder farmers' recall of pesticide use and exposure determinants over a two-year period in a low-income country context. METHODS: The Pesticide Use in Tropical Settings (PESTROP) study in Uganda consists of 302 smallholder farmers who were interviewed in 2017. In the same season in 2019, these farmers were re-questioned concerning pesticide use (e.g., use of active ingredients) and exposure information (e.g., crops, personal protective equipment [PPE], hygienic behaviours) they had previously provided. The extent of recall bias was assessed by comparing responses at follow-up in 2019 with practices and behaviours reported from the baseline interview in 2017. RESULTS: An 84% (n = 255) follow-up response rate was attained. We found instances of better recall (e.g., overall agreement >70% and Area Under the Curve (AUC) values > 0.7) for the use of some active ingredients, commonly used PPE items, and washing clothes after application, whereas only 13.3% could correctly recall their three major crops. We observed a trend where more individuals reported the use of active ingredients, while fewer reported the use of PPE items, two years later. In general, we found better agreement in the recall of years working with pesticides compared to hours per day or days per week in the field, with no apparent systematic over or under reporting by demographic characteristics. CONCLUSIONS: While some of these findings provide consistency with those from high-income countries, more research is needed on recall in poorly educated agriculture communities in low- and middle-income settings to confirm these results.

Determinants of blood and saliva lead concentrations in adult gardeners on urban agricultural sites.

Soil Pb concentrations at urban agriculture sites (UAS) commonly exceed recommended safe levels. There is a lack of evidence regarding uptake of Pb by gardeners using such sites for food crops. Our study aimed to elucidate whether gardening in soil with raised Pb levels results in Pb body burdens of concern to health, and to assess confounding factors influencing Pb body burden. Our cross-sectional case study measured Pb in saliva and blood of UAS gardeners (n = 43), soil and produce samples from their UAS, and home tap water. Blood and saliva Pb concentrations were compared with those from non-UAS gardener controls (n = 29). A health risk threshold of 5 µg dL-1 blood Pb level (BLL) was selected in keeping with international guidance. Detailed surveys investigated individuals' anthropometrics and potential Pb exposures from diet, and historic and everyday activities. Saliva was not found to be a suitable biomarker of adult Pb exposure in this context. Predictors of higher BLLs were being older, being male and eating more root vegetables and shrub fruit. Eating more green vegetables predicted a lower BLL, suggesting a protective effect against Pb uptake. UAS gardeners' BLLs (geometric mean 1.53; range 0.6-4.1 µg dL-1) were not significantly higher (p = 0.39) than the control group (geometric mean 1.43; range 0.7-2.9 µg dL-1). All BLLs were below 5 µg dL-1 except one resulting from occupational exposure. Having paired the UAS gardeners with closely matched controls, we found Pb in UAS soils (with range 62-1300 mg kg-1from common urban sources) unlikely to pose an additional risk to adult health compared to their neighbours who did not access UAS. As such, other Pb sources may be the dominant factor controlling BLL.

Gender differences in respiratory health outcomes among farming cohorts around the globe: findings from the AGRICOH consortium.

Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Improving Exposure Assessment Methodologies for Epidemiological Studies on Pesticides: Study Protocol.

BACKGROUND: Exposure to certain pesticides has been associated with several chronic diseases. However, to determine the role of pesticides in the causation of such diseases, an assessment of historical exposures is required. Exposure measurement data are rarely available; therefore, assessment of historical exposures is frequently based on surrogate self-reported information, which has inherent limitations. Understanding the performance of the applied surrogate measures in the exposure assessment of pesticides is therefore important to allow proper evaluation of the risks. OBJECTIVE: The Improving Exposure Assessment Methodologies for Epidemiological Studies on Pesticides (IMPRESS) project aims to assess the reliability and external validity of the surrogate measures used to assign exposure within individuals or groups of individuals, which are frequently based on self-reported data on exposure determinants. IMPRESS will also evaluate the size of recall bias on the misclassification of exposure to pesticides; this in turn will affect epidemiological estimates of the effect of pesticides on human health. METHODS: The IMPRESS project will recruit existing cohort participants from previous and ongoing research studies primarily of epidemiological origin from Malaysia, Uganda, and the United Kingdom. Consenting participants of each cohort will be reinterviewed using an amended version of the original questionnaire addressing pesticide use characteristics administered to that cohort. The format and relevant questions will be retained but some extraneous questions from the original (eg, relating to health) will be excluded for ethical and practical reasons. The reliability of pesticide exposure recall over different time periods (<2 years, 6-12 years, and >15 years) will then be evaluated. Where the original cohort study is still ongoing, participants will also be asked if they wish to take part in a new exposure biomonitoring survey, which involves them providing urine samples for pesticide metabolite analysis and completing questionnaire information regarding their work activities at the time of sampling. The participant's level of exposure to pesticides will be determined by analyzing the collected urine samples for selected pesticide metabolites. The biomonitoring measurement results will be used to assess the performance of algorithm-based exposure assessment methods used in epidemiological studies to estimate individual exposures during application and re-entry work. RESULTS: The project was funded in September 2017. Enrollment and sample collection was completed for Malaysia in 2019 and is on-going for Uganda and the United Kingdom. Sample and data analysis will proceed in 2020 and the first results are expected to be submitted for publication in 2021. CONCLUSIONS: The study will evaluate the consistency of questionnaire data and accuracy of current algorithms in assessing pesticide exposures. It will indicate where amendments can be made to better capture exposure data for future epidemiology studies and thus improve the reliability of exposure-disease associations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/16448.

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.

Prospective Investigation of Pesticide Applicators' Health (PIPAH) study: a cohort study of professional pesticide users in Great Britain.

PURPOSE: The purpose of the study is to monitor the exposure and health of workers in Great Britain who use pesticides as a part of their job, and to gain a better understanding of the relationship between long-term exposure to pesticides and health. PARTICIPANTS: Study participants are professional pesticide users who are certified in the safe use of pesticides or who were born before 1965 and apply pesticides under 'grandfather rights'. Overall response rate was 20%; participants are mostly male (98%) and the average age is 54 years, ranging from 17 to over 80 years. FINDINGS TO DATE: Participants have completed a baseline general questionnaire and three follow-up questionnaires on the use of pesticides. These data will enable investigations into the relationship between occupational pesticide exposure and health outcomes taking into account non-occupational confounding factors. FUTURE PLANS: There is no set end date for data collection. Recruitment into the cohort will continue, and for the foreseeable future there will be annual pesticide use questionnaires and five yearly follow-up general questionnaires.The intention is to validate the pesticide use questionnaire, and to develop a crop/job exposure matrix (C/JEM) which can be updated regularly. This C/JEM will be able to look at general categories of pesticide, such as insecticides, structurally related pesticides, such as organochlorines, or individual active ingredients. Data collected on use of personal protective equipment and method of application will provide information on how potential exposure to pesticide during application may have been modified. The study will be able to estimate changes in individual pesticide use over time, and to examine the associations between pesticide use and both baseline and long-term health outcomes.The cohort members will be linked to national databases for notification of hospital episode statistics, cancer incidence and mortality for follow-up of health outcomes.

Exposure to Diisocyanates and Their Corresponding Diamines in Seven Different Workplaces.

Biological monitoring to assess exposure to diisocyanates in the workplace is becoming increasingly widespread due to its relative ease of use and ability to look at all exposure routes. Currently, biological monitoring measures the corresponding isocyanate-derived diamine in urine, after hydrolysis. Because of this, any exposure to the diamines themselves released during the industrial process could confound the assessment of diisocyanate exposure. This paper reports an initial assessment of the extent of diamine formation and exposure during different processes involving diisocyanates including casting, grouting, core making, spray painting, foam blowing, and floor screeding. Air monitoring and glove analysis were conducted for both the relevant diisocyanate (measured as total NCO) and its corresponding diamine; urine samples were analysed (after hydrolysis) for the isocyanate-derived diamine. Processes that generated aerosols (as demonstrated by impinger analysis) such as spray painting and foam blowing were associated with the detection of diamines. Those processes that did not generate aerosols (casting, grouting, core making, and screeding) had no diamines detected, either in air or on gloves. In spray-painting tasks, diamines were a minor component (<15%) of the ambient concentration whereas in the foam blowing processes, where water is added to the process, diamine generation is more marked (up to eight times the airborne NCO concentration). Some non-aerosol processes gave rise to substantial diamine levels in urine (in exceedance of international guidance values, >5 µmol mol-1 creatinine) despite airborne levels being well within occupational exposure limits (20 µg m-3 total NCO in Great Britain); measurement data and statistical modelling indicated that skin absorption was the most likely exposure route. Foam blowing exposures were more complex, but urinary levels were greater than those expected from diisocyanate inhalation alone (measured as total NCO). This study provides evidence that biological monitoring for diisocyanates based on measuring the corresponding diamine in urine is valid, although any co-exposure to diamines themselves should be considered when interpreting results. It also demonstrates the potential for substantial skin absorption of diisocyanates in certain processes such as floor screeding and foam production.

Can the KG1 cell line be used as a model of dendritic cells and discriminate the sensitising potential of chemicals?

The KG1 myeloid leukaemia was used as source of dendritic cells (DC) to discriminate between respiratory and contact sensitising chemicals. A cocktail of cytokines was used to differentiate KG1 to dendritic like cells (termed dKG1) and the effects of nine chemicals (respiratory and contact sensitisers) and an irritant control on surface marker expression, 'antigen presenting' function and cytokine expression investigated. The stability of these chemicals when dissolved was characterised using MALDI ToF MS. A Hill plot model was used with the cellular viability data to quantify the lethal dose 50% (LD50) and a maximum sub toxic concentration of each chemical defined. Cytokine expression by the treated dKG1 was quantified using multiplex immunobead analysis. Whilst dKG1 cells were morphologically similar to DCs, expression of specific surface markers was not typical for DCs derived from healthy precursor cells. When the chemicals were applied at defined sub toxic doses no effects on dKG1 phenotype, function, or cytokine expression, attributable to the sensitisation properties were discriminated. However, dKG1 cells were much more sensitive to the toxic effects of these chemicals compared to the parent KG1 cells. Only 4 of the 9 chemicals tested were stable when dissolved indicating that the effect of sensitising chemicals on antigen presenting cells may be related to species other than the parent compound.

Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles.

Investigation of saliva as an alternative matrix to blood for the biological monitoring of inorganic lead.

INTRODUCTION: Whole blood is the established matrix for biological monitoring of inorganic lead; however blood sampling is an invasive procedure. Saliva offers a potential non-invasive alternative. This study determines lead in whole blood and saliva. A novel method for saliva sampling and preparation is presented. METHODS: Paired blood and saliva samples were obtained from 105 occupationally exposed UK workers. Saliva was collected using a StatSure sampling device, and a nitric acid digestion step was incorporated. The utility of the device for this application was evaluated. Whole blood was obtained by venepuncture. Analyses were carried out by ICP-MS. RESULTS: The limit of detection for lead in saliva was 0.011 µg/L. Mean blank-corrected recovery from 10 µg/L spiked saliva was 65.9%. The mean result from blank saliva extracted through the StatSure device was 2.86 µg/L, compared to 0.38 µg/L by direct analysis. For the paired samples, median blood lead was 6.00 µg/dL and median saliva lead was 17.1 µg/L. Pearson's correlation coefficient for saliva lead versus blood lead was 0.457 (95% C.I. 0.291-0.596). CONCLUSIONS: ICP-MS analysis allows sensitive determination of lead in saliva with low limits of detection. The StatSure device is effective for high occupational exposures, but contamination from the device could confound lower-level measurements. Saliva would only be effective as a surrogate for whole blood for highly-exposed populations, although with further work it may have applications as a biomarker of recent exposure.

The cost of hypertension-related ill-health attributable to environmental noise.

Hypertension (HT) is associated with environmental noise exposure and is a risk factor for a range of health outcomes. The study aims were to identify key HT related health outcomes and to quantify and monetize the impact on health outcomes attributable to environmental noise-related HT. A reiterative literature review identified key HT related health outcomes and their quantitative links with HT. The health impact of increases in environmental noise above recommended daytime noise levels (55 dB[A]) were quantified in terms of quality adjusted life years and then monetized. A case study evaluated the cost of environmental noise, using published data on health risks and the number of people exposed to various bands of environmental noise levels in the United Kingdom (UK). Three health outcomes were selected based on the strength of evidence linking them with HT and their current impact on society: Acute myocardial infarction (AMI), stroke and dementia. In the UK population, an additional 542 cases of HT-related AMI, 788 cases of stroke and 1169 cases of dementia were expected per year due to daytime noise levels ≥55 dB(A). The cost of these additional cases was valued at around £1.09 billion, with dementia accounting for 44%. The methodology is dependent on the availability and quality of published data and the resulting valuations reflect these limitations. The estimated intangible cost provides an insight into the scale of the health impacts and conversely the benefits that the implementation of policies to manage environmental noise may confer.

Cardiovascular disease mortality among British asbestos workers (1971-2005).

OBJECTIVES: Asbestos is an inflammatory agent, and there is evidence that inflammatory processes are involved in the development of cardiovascular disease. Whether asbestos is a risk factor for cardiovascular disease has not been established. The objective of this study was to investigate cardiovascular disease mortality in a large cohort of workers occupationally exposed to asbestos. METHODS: Cardiovascular disease mortality in a cohort of 98,912 asbestos workers, with median follow-up of 19 years, was analysed. Unadjusted and smoking-adjusted standardised mortality ratios (SMRs) were calculated. The association between indicators of asbestos exposure and mortality was analysed with Poisson regression models, for deaths occurring during the period 1971-2005. RESULTS: Altogether 15,557 deaths from all causes, 1053 deaths from cerebrovascular disease and 4185 deaths from ischaemic heart disease (IHD) occurred during follow-up. There was statistically significant excess mortality from cerebrovascular disease (SMR: men 1.63, women 2.04) and IHD (SMR: men 1.39, women 1.89). Job and birth cohort were associated with the risk of cerebrovascular and IHD mortality in the Poisson regression model including sex, age, smoking status, job, cohort and duration of exposure. For IHD only, duration of exposure was also statistically significant in this model. CONCLUSIONS: Cerebrovascular and IHD mortality was significantly higher among these asbestos workers than in the general population and within the cohort mortality was associated with indicators of asbestos exposure. These findings provide some evidence that occupational exposure to asbestos was associated with cardiovascular disease mortality in this group of workers.

The effect of smoking on the risk of lung cancer mortality for asbestos workers in Great Britain (1971-2005).

OBJECTIVES: Workers in the asbestos industry tend to have high smoking rates compared to the general population. Both asbestos exposure and cigarette smoking are recognized risk factors for lung cancer mortality, but the exact nature of the interaction between the two remains uncertain. The aim of this study was to examine the effect of smoking and smoking cessation among asbestos workers in Great Britain (GB) and investigate the interaction between asbestos exposure and smoking. METHODS: The study population consisted of 98 912 asbestos workers recruited into the GB Asbestos Survey from 1971, followed-up to December 2005. Poisson regression was used to estimate relative risks of lung cancer mortality associated with smoking habits of the asbestos workers and to assess whether these effects differed within various categories of asbestos exposure. The interaction between asbestos exposure and smoking was examined using the Synergy (S) and Multiplicativity (V) indices, which test the hypotheses of additive and multiplicative interaction, respectively. The proportion of lung cancers among smokers attributable to the interaction of asbestos and smoking was also estimated. RESULTS: During 1 780 233 person-years of follow-up, there were 1878 deaths from lung cancer (12% of all deaths). Risk of lung cancer mortality increased with packs smoked per day, smoking duration, and total smoke exposure (pack-years). Asbestos workers who stopped smoking remained at increased risk of lung cancer mortality up to 40 years after smoking cessation compared to asbestos workers who never smoked. The effects of smoking and stopping smoking did not differ by duration of asbestos exposure, main occupation, age at first asbestos exposure, year of first exposure, or latency period. The interaction between asbestos exposure and smoking for asbestos workers was greater than additive [S 1.4, 95% confidence interval (CI) 1.2-1.6], and the multiplicative hypothesis could not be rejected (V 0.9, 95% CI 0.3-2.4). For those asbestos workers who smoked, an estimated 26% (95% CI 14-38%) of lung cancer deaths were attributable to the interaction of asbestos and smoking. CONCLUSIONS: This study emphasizes the importance of smoking prevention and cessation among those who work in the asbestos industry.

Asbestosis and mesothelioma among British asbestos workers (1971-2005).

BACKGROUND: Ascertainment of asbestosis and mesothelioma from underlying cause of death underestimates the burden of these diseases. The aims of this study were to estimate the true frequency of asbestosis and mesothelioma among asbestos workers in Great Britain (GB), and to identify factors associated with the risk of death with these diseases. METHODS: The GB Asbestos Survey was established in 1971 to monitor long-term health outcomes among workers covered by regulations to control asbestos at work. Asbestosis and mesothelioma cases were defined by multiple cause of death, and were ascertained by identifying asbestos workers on the GB Asbestosis and Mesothelioma Registers. Standardized mortality ratios (SMRs) were calculated; the risks of asbestosis and mesothelioma were modeled with Poisson regression analysis. Deaths to the end of 2005 were included. RESULTS: There were 15,557 deaths between 1971 and 2005 among the 98,912 workers. Altogether 477 asbestosis and 649 mesothelioma cases were identified. The SMR for all causes was 1.42, for asbestosis 51.3, and for mesothelioma 13.5. In multiply adjusted analysis, age, sex, job, and birth cohort were significantly associated with asbestosis and mesothelioma. For asbestosis year of first exposure, and for mesothelioma latency, were also statistically significant. CONCLUSIONS: The asbestos workers experienced high mortality from all causes, asbestosis, and mesothelioma. There was some evidence that the risk of asbestosis and mesothelioma was lower in later birth cohorts and among those first occupationally exposed to asbestos more recently. Due to the long latency of both diseases, further follow-up is required to confirm these trends.

The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis.

The peroxisome proliferator-activated receptor-gamma gene (PPARG) has been implicated in the etiology of type 2 diabetes mellitus and has been investigated in numerous epidemiologic studies. In this Human Genome Epidemiology review, the authors assessed this relation in an updated meta-analysis of 60 association studies. Electronic literature searches were conducted on September 14, 2009. Population-based cohort, case-control, cross-sectional, or genome-wide association studies reporting associations between the PPARG Pro12Ala gene variant (rs1801282) and type 2 diabetes were included. An updated literature-based meta-analysis involving 32,849 type 2 diabetes cases and 47,456 controls in relation to the PPARG Pro12Ala variant was conducted. The combined overall odds ratio, calculated by per-allele genetic model random-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, was 0.86 (95% confidence interval: 0.81, 0.90). The analysis indicated a moderate level of heterogeneity attributable to genuine variation in gene effect size (I(2) = 37%). This may reflect the variation observed between ethnic populations and/or differences in body mass index. Work on PPARG Pro12Ala should now focus on the observed heterogeneity in the magnitude of the association between populations. Further investigations into gene-gene and gene-environment interactions may prove enlightening.

Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study.

BACKGROUND: Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus, but the evidence is limited and inconclusive. Plasma vitamin C level is a good biomarker of fruit and vegetable intake, but, to our knowledge, no prospective studies have examined its association with diabetes risk. This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes. METHODS: We administered a semiquantitative food frequency questionnaire to men and women from a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk) study who were aged 40 to 75 years at baseline (1993-1997) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed. During 12 years of follow-up between February 1993 and the end of December 2005, 735 clinically incident cases of diabetes were identified among 21 831 healthy individuals. We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels. RESULTS: A strong inverse association was found between plasma vitamin C level and diabetes risk. The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 (95% confidence interval, 0.28-0.52) in a model adjusted for demographic, lifestyle, and anthropometric variables. In a similarly adjusted model, the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 (95% confidence interval, 0.60-1.00). CONCLUSIONS: Higher plasma vitamin C level and, to a lesser degree, fruit and vegetable intake were associated with a substantially decreased risk of diabetes. Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes.