Occupational exposure to pesticides and neurobehavioral outcomes. Impact of different original and recalled exposure measures on the associations.

BACKGROUND: Several measures of occupational exposure to pesticides have been used to study associations between exposure to pesticides and neurobehavioral outcomes. This study assessed the impact of different exposure measures for glyphosate and mancozeb on the association with neurobehavioral outcomes based on original and recalled self-reported data with 246 smallholder farmers in Uganda. METHODS: The association between the 6 exposure measures and 6 selected neurobehavioral test scores was investigated using linear multivariable regression models. Exposure measures included original exposure measures for the previous year in 2017: (i) application status (yes/no), (ii) number of application days, (iii) average exposure-intensity scores (EIS) of an application and (iv) number of EIS-weighted application days. Two additional measures were collected in 2019: (v) recalled application status and (vi) recalled EIS for the respective periods in 2017. RESULTS: Recalled applicator status and EIS were between 1.2 and 1.4 times more frequent and higher for both pesticides than the original application status and EIS. Adverse associations between the different original measures of exposure to glyphosate and 4 neurobehavioral tests were observed. Glyphosate exposure based on recalled information and all mancozeb exposure measures were not associated with the neurobehavioral outcomes. CONCLUSIONS: The relation between the different original self-reported glyphosate exposure measures and neurobehavioral test scores appeared to be robust. When based on recalled exposure measures, associations observed with the original exposure measures were no longer present. Therefore, future epidemiological studies on self-reported exposure should critically evaluate the potential bias towards the null in observed exposure-response associations.

Estimating occupational disease burden: a way forward.

Estimates of occupational disease burden provide important information on which effective policy and regulations can be developed. However, there is no direct way that these data can be obtained, and most burden estimates are derived by merging different data from diverse sources to synthesize estimates of the number of people made ill or who have died from workplace exposures. In recent years, several research groups have published estimates of occupational health burden at national or global scales; these are not always consistent. The World Health Organisation and the International Labour Organisation have taken on the task of producing occupational disease burden estimates for several workplace agents, which we assume are to be seen as the definitive global, regional, and national data. In this commentary, we critique the WHO/ILO approach for their estimates of the non-melanoma skin cancer burden from solar ultraviolet radiation and some of their results for hazardous particulates. We provide recommendations for researchers undertaking occupational burden estimates that they should report along with their data.

Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996-2019.

BACKGROUND: Occupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual's health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time. AIMS: This study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK. METHODS: Cases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data. RESULTS: Of cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period. CONCLUSIONS: Over 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.

Trends in occupational and work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK: findings from The Health and Occupation Research network 1996-2019.

BACKGROUND: Occupational exposure to metals such as nickel, chromium and cobalt can be associated with contact dermatitis, which can adversely affect an individual's health, finances and employment. Despite this, little is known about the incidence of metal-related occupational contact dermatitis over prolonged periods of time. OBJECTIVES: To investigate the medically reported trends in the incidence of work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK. METHODS: Incidence and trends in cases of occupational contact dermatitis caused by nickel, chromium or cobalt between 1996 and 2019 (inclusive), reported to the EPIDERM surveillance scheme, were investigated and compared with trends in the incidence of occupational contact dermatitis attributed to agents other than the aforementioned metals. A sensitivity analysis restricting the study cohort to cases attributed to only one type of metal was also conducted. RESULTS: Of all cases reported to EPIDERM during the study period, 2374 (12%) were attributed to nickel, chromium or cobalt. Cases predominantly comprised females (59%), with a mean (SD) age (males and females) of 38 (13) years. Cases were most frequently reported in manufacturing, construction, and human health and social activity industries. The most frequently reported occupations were hairdressing, and sales and retail (assistants, cashiers and checkout operators). The highest annual incidence rate of contact dermatitis was observed in females (2.60 per 100 000 persons employed per year), with the first and second peak seen in those aged 16-24 and ≥ 65 years, respectively. A statistically significant decrease in the incidence of occupational contact dermatitis attributed to metals over the study period was observed for all occupations (annual average change -6.9%, 95% confidence interval -7.8 to -5.9), with much of the decrease occurring between 1996 and 2007. Similar findings were obtained in the sensitivity analyses. CONCLUSIONS: Over a period of 24 years, there has been a statistically significant decline in the incidence of metal-related occupational contact dermatitis in the UK. This could be attributed not only to improvements in working conditions, which have reduced metal exposure, but could also be due to the closure of industries in the UK that might have generated cases of contact dermatitis owing to metal exposure.

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.

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Development of a quantitative North and Central European job exposure matrix for wood dust.

Wood dust is an established carcinogen also linked to several non malignant respiratory disorders. A major limitation in research on wood dust and its health effects is the lack of (historical) quantitative estimates of occupational exposure for use in general population-based case-control or cohort studies. The present study aimed to develop a multinational quantitative Job Exposure Matrix (JEM) for wood dust exposure using exposure data from several Northern and Central European countries. For this, an occupational exposure database containing 12653 personal wood dust measurements collected between 1978 and 2007 in Denmark, Finland, France, The Netherlands, Norway, and the United Kingdom (UK) was established. Measurement data were adjusted for differences in inhalable dust sampling efficiency resulting from the use of different dust samplers and analysed using linear mixed effect regression with job codes (ISCO-88) and country treated as random effects. Fixed effects were the year of measurement, the expert assessment of exposure intensity (no, low, and high exposure) for every ISCO-88 job code from an existing wood dust JEM and sampling duration. The results of the models suggest that wood dust exposure has declined annually by approximately 8%. Substantial differences in exposure levels between countries were observed with the highest levels in the United Kingdom and the lowest in Denmark and Norway, albeit with similar job rankings across countries. The jobs with the highest predicted exposure are floor layers and tile setters, wood-products machine operators, and building construction labourers with geometric mean levels for the year 1997 between 1.7 and 1.9 mg/m3. The predicted exposure estimates by the model are compared with the results of wood dust measurement data reported in the literature. The model predicted estimates for full-shift exposures were used to develop a time-dependent quantitative JEM for exposure to wood dust that can be used to estimate exposure for participants of general population studies in Northern European countries on the health effects from occupational exposure to wood dust.

Validation of a COVID-19 Job Exposure Matrix (COVID-19-JEM) for Occupational Risk of a SARS-CoV-2 Infection at Work: Using Data of Dutch Workers.

OBJECTIVES: A COVID-19 Job Exposure Matrix (COVID-19-JEM) has been developed, consisting of four dimensions on transmission, two on mitigation measures, and two on precarious work. This study aims to validate the COVID-19-JEM by (i) comparing risk scores assigned by the COVID-19-JEM with self-reported data, and (ii) estimating the associations between the COVID-19-JEM risk scores and self-reported COVID-19. METHODS: Data from measurements 2 (July 2020, n = 7690) and 4 (March 2021, n = 6794) of the Netherlands Working Conditions Survey-COVID-19 (NWCS-COVID-19) cohort study were used. Responses to questions related to the transmission risks and mitigation measures of Measurement 2 were used to calculate self-reported risk scores. These scores were compared with the COVID-19-JEM attributed risk scores, by assessing the percentage agreement and weighted kappa (κ). Based on Measurement 4, logistic regression analyses were conducted to estimate the associations between all COVID-19-JEM risk scores and self-reported COVID-19 (infection in general and infected at work). RESULTS: The agreement between the COVID-19-JEM and questionnaire-based risk scores was good (κ ≥ 0.70) for most dimensions, except work location (κ = 0.56), and face covering (κ = 0.41). Apart from the precarious work dimensions, higher COVID-19-JEM assigned risk scores had higher odds ratios (ORs; ranging between 1.28 and 1.80) on having had COVID-19. Associations were stronger when the infection were thought to have happened at work (ORs between 2.33 and 11.62). CONCLUSIONS: Generally, the COVID-19-JEM showed a good agreement with self-reported infection risks and infection rates at work. The next step is to validate the COVID-19-JEM with objective data in the Netherlands and beyond.

Paternal Occupational Exposure to Heavy Metals and Welding Fumes and Testicular Germ Cell Tumours in Sons in France.

Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case-control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.

Occupational inhalational accidents: analysis of cases from the UK SWORD reporting scheme from 1999 to 2018.

OBJECTIVE: To estimate the reported UK incidence of occupational inhalation accidents, and to consider changes of incidence and potential causes over time. METHODS: Cases of occupational inhalation accident reported to Surveillance of Work Related Occupational Respiratory Diseases (SWORD) over 20 years were grouped into four 5-year time periods. Cases were characterised by causative exposure, occupation and industrial sector. Incidence rates were calculated using Office of National Statistics employment data. RESULTS: The 172 actual cases reported to SWORD equated to an estimated 502 cases after adjusting for reporting frequency. Their mean age was 41.3 years (SD 12.3); 77% were male. The annual incidence fell from 1.7 per million employed in the first 5-year period, to 0.5 in the most recent. The most common occupations, responsible for 35% of all cases, were in descending order (number, % of total cases): Labourers in process and plant operations (8, 4.7), welding trades (8, 4.7), fire service officers (8, 4.7), heavy goods vehicle drivers (7, 4.1), metal working production and maintenance fitters (7, 4.1), civil service administrative officers and assistants (7, 4.1), food, drink and tobacco process operatives (6, 3.5), and three summated categories of elementary and service occupations including cleaners and domestics (10, 5.8).Three of 40 exposure categories were common to all time periods; acids (19.6% of all cases 1999-2004, 2.3% 2005-2009, 6.3% 2010-2013, 6.3% 2014-2018), chlorine/hypochlorites (7.2%, 7.0%, 2.5%, 6.3%, respectively) and solvents (14.4%, 11.6%, 12.5%, 6.3%, respectively). CONCLUSIONS: The incidence of inhalation accidents appears to have fallen, although certain exposures appear to be persistently linked to cases.

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.

Changing patterns of sickness absence among healthcare workers in England during the COVID-19 pandemic.

BACKGROUND: Patterns of sickness absence shed useful light on disease occurrence and illness-related behaviours in working populations. METHODS: We analysed prospectively collected, pseudonymized data on 959 356 employees who were continuously employed by National Health Service trusts in England from 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019. RESULTS: After exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019. Trends for specific categories of illness varied substantially, with a fall by 24% for cancer, but an increase for mental illness. A doubling of new absences for pregnancy-related disorders during May-July of 2020 was limited to women with earlier COVID-19 sickness absence. CONCLUSIONS: Various factors will have contributed to the large and divergent changes that were observed. The findings reinforce concerns regarding delays in diagnosis and treatment of cancers and support a need to plan for a large backlog of treatment for many other diseases. Further research should explore the rise in absence for pregnancy-related disorders among women with earlier COVID-19 sickness absence.

Respiratory health and silicosis in artisanal mine workers in southern Brazil.

BACKGROUND: Artisanal and small-scale mining (ASM) are an important source of employment in southern Brazil. Mining workers are frequently exposed to unhealthy work conditions which increase the risk of occupational diseases. In this study, we assessed the association of sociodemographic factors and the occupational history of artisanal mining workers with the risk of adverse respiratory outcomes. METHODS: The study was conducted with 258 artisanal mining workers in southern Brazil, who were exposed to dust (mainly crystalline silica) in their work. Information on sociodemographic variables and occupational histories was collected between 2017 and 2018. To estimate the worker's exposure to inhalable dust we use the Advanced REACH (Registration, Evaluation, and Authorization of Chemicals) Tool (ART). RESULTS: Study participants were all men, with an average age of 40 years. Median crude dust exposure estimated by ART was 13.2 mg/m³ and median crude crystalline silica exposure was 1.6 mg/m3 . The prevalence ratio (PR) for self-reported silicosis was 3.08 (95% confidence interval, 1.39-7.17) in workers with 20 years or more of mining work. Factors associated with silicosis were age, pack-years of tobacco use, and body mass index. Smokers were over twice as likely to report respiratory symptoms. CONCLUSIONS: Our findings indicate that a high prevalence of silicosis and other associated diseases in mining workers is associated with both unhealthy work environment conditions and the health profile of workers. This study is an important step for understanding health outcomes from work in ASM.

Life Course Air Pollution Exposure and Cognitive Decline: Modelled Historical Air Pollution Data and the Lothian Birth Cohort 1936.

BACKGROUND: Air pollution has been consistently linked with dementia and cognitive decline. However, it is unclear whether risk is accumulated through long-term exposure or whether there are sensitive/critical periods. A key barrier to clarifying this relationship is the dearth of historical air pollution data. OBJECTIVE: To demonstrate the feasibility of modelling historical air pollution data and using them in epidemiologicalmodels. METHODS: Using the EMEP4UK atmospheric chemistry transport model, we modelled historical fine particulate matter (PM2.5) concentrations for the years 1935, 1950, 1970, 1980, and 1990 and combined these with contemporary modelled data from 2001 to estimate life course exposure in 572 participants in the Lothian Birth Cohort 1936 with lifetime residential history recorded. Linear regression and latent growth models were constructed using cognitive ability (IQ) measured by the Moray House Test at the ages of 11, 70, 76, and 79 years to explore the effects of historical air pollution exposure. Covariates included sex, IQ at age 11 years, social class, and smoking. RESULTS: Higher air pollution modelled for 1935 (when participants would have been in utero) was associated with worse change in IQ from age 11-70 years (ß = -0.006, SE = 0.002, p = 0.03) but not cognitive trajectories from age 70-79 years (p > 0.05). There was no support for other critical/sensitive periods of exposure or an accumulation of risk (all p > 0.05). CONCLUSION: The life course paradigm is essential in understanding cognitive decline and this is the first study to examine life course air pollution exposure in relation to cognitive health.

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.

Occupational and work-related respiratory disease attributed to cleaning products.

OBJECTIVES: Exposure to cleaning products has been associated with adverse respiratory outcomes. This study aimed to investigate the medically reported incidence, trends in incidence and occupational determinants of work-related respiratory disorders attributed to cleaning agents and to explore the role of 'Quantitative Structure Activity Relationships' (QSAR) in corroborating the identification of chemical respiratory sensitisers. METHODS: Respiratory diagnoses attributed to cleaning agents were extracted from The Health and Occupation Research (THOR) surveillance network, 1989-2017. Incidence, trends in incidence and incidence rate ratios by occupation were investigated. Agents were classified by chemical type and QSAR hazard indices were determined for specific organic chemicals. RESULTS: Approximately 6% (779 cases) of the (non-asbestos) THOR respiratory cases were attributed to cleaning agents. Diagnoses were predominantly asthma (58%) and inhalation accidents (27%) with frequently reported chemical categories being aldehydes (30%) and chlorine/its releasers (26%). No significant trend in asthma incidence (1999-2017) was observed (annual average change of -1.1% (95% CI -4.4 to 2.4)). This contrasted with a statistically significant annual decline in asthma incidence (-6.8% (95% CI -8.0 to -5.6)) for non-cleaning agents. There was a large variation in risk between occupations. 7 of the 15 organic chemicals specifically identified had a QSAR generated hazard index consistent with being a respiratory sensitiser. CONCLUSION: Specific occupations appear to be at increased risk of adverse respiratory outcomes attributed to cleaning agents. While exposure to agents such as glutaraldehyde have been addressed, other exposures, such as to chlorine, remain important. Chemical features of the cleaning agents helped distinguish between sensitising and irritant agents.

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.