Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran.

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.

International perspective on military exposure data sources, applications, and opportunities for collaboration.

Military personnel may be exposed to a range of hazards. The assessment, documentation and reporting of military exposure information are important steps to guide health protection, services, and research to support actively serving members and veterans. In 2021, a Working Group of researchers from veteran and defense administrations across the Five Eyes countries (Australia, Canada, New Zealand, the United Kingdom, and the United States) was established to examine large military exposure data sources available in each country, their applications, and opportunities to leverage information across administrations and internationally. We provide a brief summary of this work here to highlight some successful examples of data applications and to elicit interest in this evolving area of exposure science.

Prevalence and Correlates of Military Sexual Trauma in Service Members and Veterans: Results From the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey.

INTRODUCTION: Military sexual trauma (MST) is an ongoing problem. We used a 2002 population-based sample, followed up in 2018, to examine: (1) the prevalence of MST and non-MST in male and female currently serving members and veterans of the Canadian Armed Forces, and (2) demographic and military correlates of MST and non-MST. METHODS: Data came from the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (n = 2,941, ages 33 years + ). Individuals endorsing sexual trauma were stratified into MST and non-MST and compared to individuals with no sexual trauma. The prevalence of lifetime MST was computed, and correlates of sexual trauma were examined using multinomial regression analyses. RESULTS: The overall prevalence of MST was 44.6% in females and 4.8% in males. Estimates were comparable between currently serving members and veterans. In adjusted models in both sexes, MST was more likely among younger individuals (i.e., 33-49 years), and MST and non-MST were more likely in those reporting more non-sexual traumatic events. Among females, MST and non-MST were more likely in those reporting lower household income, non-MST was less likely among Officers, and MST was more likely among those with a deployment history and serving in an air environment. Unwanted sexual touching by a Canadian military member or employee was the most prevalent type and context of MST. INTERPRETATION: A high prevalence of MST was observed in a follow-up sample of Canadian Armed Forces members and veterans. Results may inform further research as well as MST prevention efforts.

Lessons Learned From Presumptive Condition Lists in Veteran Compensation Systems.

Presumptive condition lists formally accept connections between military factors and veteran health conditions. An environmental scan of such lists and their evidentiary basis was conducted across four veterans' administrations to inform other administrations considering the development of such lists. Information on included conditions, qualifying military factors, and scientific processes was obtained through targeted internet searches and correspondence with veterans' administrations. The content of presumptive condition lists across jurisdictions varied by conditions included, as well as military eligibility requirements (e.g., service in particular conflict, context, or time period). Scientific review processes to develop lists also varied across jurisdictions. Findings indicate that evidence and experience may be leveraged across compensation systems (veteran and civilian). Ongoing research to understand links between military exposures and veteran health is recommended.

Comparing negative health indicators in male and female veterans with the Canadian general population.

INTRODUCTION: Sex-based information on differences between Canadian veterans and the general population is important to understand veterans' unique health needs and identify areas requiring further research. This study compared various health indicators in male and female veterans with their Canadian counterparts. METHODS: Health indicators for recent-era Regular Force veterans (released between 1998 and 2015) were obtained from the 2016 Life After Service Survey and compared with the general population in the 2015-16 Canadian Community Health Survey using a cross-sectional approach. Age-adjusted rates and 95% CIs were calculated for males and females separately. RESULTS: Compared with Canadians, veterans (both sexes) reported higher prevalence of fair or poor health and mental health, needing help with one or more activity of daily living, lifetime suicidal ideation and being diagnosed with mood and anxiety disorders, post-traumatic stress disorder, migraines, back problems, chronic pain, arthritis, ever having cancer, hearing problems, chronic pain and gastrointestinal problems. A higher prevalence of cardiovascular disease (all types) and high blood pressure was observed in male veterans compared with their Canadian counterparts. Within veterans only, males reported a higher prevalence of diagnosed hearing problems and cardiovascular disease compared with females; conversely females reported a higher prevalence of diagnosed migraines, mood, anxiety and gastrointestinal disorders, and needing help with activities of daily living. These sex differences are similar to the Canadian general population. Some similarities in reporting prevalence between male and female veterans (eg, fair or poor mental health, lifetime suicidal ideation, arthritis, asthma, lifetime cancer incidence, chronic pain and diabetes) were not observed in other Canadians. CONCLUSION: Male and female veterans differed from comparable Canadians, and from each other, in various areas of health. Further research is needed to explore these findings, and veteran-based policies and services should consider sex differences.

Barriers and facilitators for the safe handling of antineoplastic drugs.

INTRODUCTION: Antineoplastic drugs are widely used in the treatment of cancer. However, some are known carcinogens and reproductive toxins, and incidental low-level exposure to workers is a health concern. CAREX Canada estimated that approximately 75,000 Canadians are exposed to antineoplastic drugs in workplace settings. While policies and guidelines on safe handling of antineoplastic drugs are available, evidence suggests that compliance is low. In this paper, we identify barriers and facilitators for safe handling of antineoplastic drugs in workplace settings. METHODS: We utilized a unique method to study public policy which involved compiling policy levers, developing a logic model, conducting a literature review, and contextualizing data through a deliberative process with stakeholders to explore in-depth contextual factors and experiences for the safe handling of antineoplastic drugs. RESULTS: The most common barriers identified in the literature were: poor training (46%), poor safety culture (41%), and inconsistent policies (36%). The most common facilitators were: adequate safety training (41%), leadership support (23%), and consistent policies (21%). Several of these factors are intertwined and while this means one barrier can cause other barriers, it also allows healthcare employers to mitigate these barriers by implementing small but meaningful changes in the workplace. CONCLUSION: The combination of barriers and facilitators identified in our review highlight the importance of creating work environments where safety is a priority for the safe handling of antineoplastic drugs. The results of this study will assist policy makers and managers in identifying gaps and enhancing strategies that reduce occupational exposure to antineoplastic drugs.

Occupational Exposure to Carcinogens and Occupational Epidemiological Cancer Studies in Iran: A Review.

INTRODUCTION: The extent of exposure to occupational carcinogens is not well characterized in Iran, and little is known about the burden of occupational cancer. OBJECTIVES: This study aimed to describe exposure to occupational carcinogens and occupational epidemiology studies in Iran. METHODS: Relevant studies up to January 2021 in Iran were identified through three databases (PubMed, Web of Science, and Google Scholar). RESULTS: Forty-nine publications from 2009 to 2020 (one cohort, 11 case-control, 34 exposure monitoring studies, and three cancer burden studies) were included. The exposure monitoring studies were conducted mainly in the petroleum industry, metal industry, manufacturing of electronics, manufacturing of plastics, construction industry, and service industry. A few of the case-control studies also reported increased risk of cancers in relation to work in those industries. CONCLUSIONS: Occupational cancer epidemiology in Iran is at an early stage. Both epidemiological and exposure monitoring studies are generally limited in size to provide robust evidence of occupational cancer risks. A coherent strategy to estimate the occupational cancer burden in Iran should start with conducting epidemiological studies along with systematic monitoring of occupational carcinogens for use in hazard control and research.

Health care access and use among male and female Canadian Armed Forces veterans.

BACKGROUND: Veterans are more likely than other Canadians to have chronic health conditions, making access to health care an important issue. However, little research has addressed health care access and use among veterans. This paper examines access and use among veterans compared with other Canadians. DATA AND METHODS: Health care access and use indicators were examined for Regular Force veterans using the 2016 Life After Service Survey. Information for male and female veterans was compared with information on the Canadian general population from the 2015 and 2016 Canadian Community Health Survey, using age-adjusted rates and 95% confidence intervals. RESULTS: More than 80% of male and female veterans reported having a regular medical doctor in the 12 months before the survey. The majority of veterans (71% of males and 81% of females) had consulted a family doctor, while a minority had been hospitalized (8% of males and females). These rates were similar to those in the Canadian general population. However, veteran consultation rates for mental health care and with audiologists, speech therapists or occupational therapists among both sexes were double to triple those of the Canadian general population. Among veterans, males reported lower rates of unmet needs compared with females. DISCUSSION: Veterans had similar rates of access to a regular medical doctor and higher rates of use compared with other Canadians. However, these may be comparatively low, given previous findings on higher rates of disability and some chronic conditions among veterans. Noted differences between males and females highlight the importance of research and services that account for sex and gender. The extent to which health care needs explain health care use and barriers to care requires further research.

Considering Exposure Assessment in Epidemiological Studies of Chronic Health in Military Populations.

Exposure assessment is an important factor in all epidemiological research seeking to identify, evaluate, and control health risks. In the military and veteran context, population health research to explore exposure-response links is complicated by the wide variety of environments and hazards encountered during active service, long latency periods, and a lack of information on exposures in potentially vulnerable subgroups. This paper summarizes some key considerations for exposure assessment in long-term health studies of military populations, including the identification of hazards related to military service, characterization of potentially exposed groups, exposure data collection, and assignment of exposures to estimate health risks. Opportunities and future directions for exposure assessment in this field are also discussed.

Prevalence and Recent Trends in Exposure to Night Shiftwork in Canada.

OBJECTIVES: Night shiftwork has been linked to various health outcomes. Knowing where and to what extent workers are exposed to this type of shiftwork can help prioritize areas for intervention and further study. This study describes recent estimates of exposure to night shiftwork in Canada for 2011, and temporal trends from 1997 to 2010. METHODS: Estimates by occupation, industry, province, and sex were calculated using data from the Survey of Labour and Income Dynamics (SLID) from 1996 to 2011. Workers who reported rotating or regular night shifts were classified as exposed to shiftwork involving nights, while those reporting other types of shiftwork, outside of regular daytime and evening shifts, were classified as possibly exposed. Results, with 97.5% confidence intervals (CIs), were summarized for three exposure categories: exposed workers, possibly exposed workers, and evening shift workers. Trends in 3-year rolling averages were described. RESULTS: In 2011, approximately 1.8 million Canadians (97.5% CI, 1.7-1.8 million), or 12% of the working population (97.5% CI, 11-12%), were exposed to night shiftwork; 45% were female. An additional 2.6 million were possibly exposed (97.5% CI, 2.5-2.7 million workers), and 745 000 worked evening shifts (97.5% CI, 701 000-792 000). This amounts to 17% (97.5% CI, 17-18%) and 4.9% (97.5% CI, 4.6-5.2%) of the labour force, respectively. Industries with the highest prevalence were accommodation and food services (20%; 97.5% CI, 18-22%), forestry, fishing, mining, oil, and gas (19%; 97.5% CI, 16-23%), and healthcare and social assistance (18%; 97.5% CI, 17-19%). By occupation, the highest prevalence of exposure was in occupations in protective services (37%; 97.5% CI, 32-42%), professional occupations in health (35%; 97.5% CI, 32-39%), and machine operators and assemblers in manufacturing (24%; 97.5% CI, 22-28%). The overall number of exposure workers increased by 29% from 1997 to 2010, but the overall proportion remained relatively the same (11% and 12%, respectively). The proportion of female workers exposed increased by 2%. CONCLUSIONS: These estimates characterize exposure to night shiftwork in Canada. Continued collection of shiftwork data, with greater detail on scheduling, workplace and personal factors, is needed for high-quality surveillance and investigations of shiftwork and health.

The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.

Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix.

INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Effect of work schedule on prospective antidepressant prescriptions in Sweden: a 2-year sex-stratified analysis using national drug registry data.

INTRODUCTION: Depression-related mood disorders affect millions of people worldwide and contribute to substantial morbidity and disability, yet little is known about the effects of work scheduling on depression. This study used a large Swedish survey to prospectively examine the effects of work schedule on registry-based antidepressant prescriptions in females and males over a 2-year period. METHODS: The study was based on an approximately representative sample (n=3980 males, 4663 females) of gainfully employed participants in the Swedish Longitudinal Occupational Survey of Health. Sex-stratified analyses were conducted using logistic regression. For exposure, eight categories described work schedule in 2008: 'regular days' (three categories of night work history: none, ≤3 years, 4+ years), 'night shift work', 'regular shift work (no nights)', 'rostered work (no nights)', 'flexible/non-regulated hours' and 'other'. For the primary outcome measure, all prescriptions coded N06A according to the Anatomical Therapeutic Chemical System were obtained from the Swedish National Prescribed Drug Register and dichotomised into 'any' or 'no' prescriptions between 2008 and 2010. Estimates were adjusted for potential sociodemographic, health and work confounders, and for prior depressive symptoms. RESULTS: In 2008, 22% of females versus 19% of males worked outside of regular daytime schedule. Registered antidepressant prescription rates in the postsurvey period were 11.4% for females versus 5.8% for males. In fully adjusted models, females in 'flexible/non-regulated' schedules showed an increased OR for prospective antidepressant prescriptions (OR=2.01, 95% CI=1.08 to 3.76). In males, odds ratios were most increased in those working 'other' schedules (OR=1.72, 95% CI=0.75 to 3.94) and 'Regular days with four or more years' history of night work' (OR=1.54, 95% CI=0.93 to 2.56). CONCLUSIONS: This study's findings support a relationship between work schedule and prospective antidepressant prescriptions in the Swedish workforce. Future research should continue to assess sex-stratified relationships, using detailed shift work exposure categories and objective registry data where possible.

Soil multifunctionality and drought resistance are determined by plant structural traits in restoring grassland.

It is increasingly recognized that belowground responses to vegetation change are closely linked to plant functional traits. However, our understanding is limited concerning the relative importance of different plant traits for soil functions and of the mechanisms by which traits influence soil properties in the real world. Here we test the hypothesis that taller species, or those with complex rooting structures, are associated with high rates of nutrient and carbon (C) cycling in grassland. We further hypothesized that communities dominated by species with deeper roots may be more resilient to drought. These hypotheses were tested in a 3-yr grassland restoration experiment on degraded ex-arable land in southern England. We sowed three trait-based plant functional groups, assembled using database derived values of plant traits, and their combinations into bare soil. This formed a range of plant trait syndromes onto which we superimposed a simulated drought 2 yr after initial establishment. We found strong evidence that community weighted mean (CWM) of plant height is negatively associated with soil nitrogen cycling and availability and soil multifunctionality. We propose that this was due to an exploitative resource capture strategy that was inappropriate in shallow chalk soils. Further, complexity of root architecture was positively related to soil multifunctionality throughout the season, with fine fibrous roots being associated with greater rates of nutrient cycling. Drought resistance of soil functions including ecosystem respiration, mineralization, and nitrification were positively related to functional divergence of rooting depth, indicating that, in shallow chalk soils, a range of water capture strategies is necessary to maintain functions. Finally, after 3 yr of the experiment, we did not detect any links between the plant traits and microbial communities, supporting the finding that traits based on plant structure and resource foraging capacity are the main variables driving soil function in the early years of grassland conversion. We suggest that screening recently restored grassland communities for potential soil multifunctionality and drought resilience may be possible based on rooting architecture and plant height. These results indicate that informed assembly of plant communities based on plant traits could aid in the restoration of functioning in degraded soil.

Priority Setting for Occupational Cancer Prevention.

BACKGROUND: Selecting priority occupational carcinogens is important for cancer prevention efforts; however, standardized selection methods are not available. The objective of this paper was to describe the methods used by CAREX Canada in 2015 to establish priorities for preventing occupational cancer, with a focus on exposure estimation and descriptive profiles. METHODS: Four criteria were used in an expert assessment process to guide carcinogen prioritization: (1) the likelihood of presence and/or use in Canadian workplaces; (2) toxicity of the substance (strength of evidence for carcinogenicity and other health effects); (3) feasibility of producing a carcinogen profile and/or an occupational estimate; and (4) special interest from the public/scientific community. Carcinogens were ranked as high, medium or low priority based on specific conditions regarding these criteria, and stakeholder input was incorporated. Priorities were set separately for the creation of new carcinogen profiles and for new occupational exposure estimates. RESULTS: Overall, 246 agents were reviewed for inclusion in the occupational priorities list. For carcinogen profile generation, 103 were prioritized (11 high, 33 medium, and 59 low priority), and 36 carcinogens were deemed priorities for occupational exposure estimation (13 high, 17 medium, and 6 low priority). CONCLUSION: Prioritizing and ranking occupational carcinogens is required for a variety of purposes, including research, resource allocation at different jurisdictional levels, calculations of occupational cancer burden, and planning of CAREX-type projects in different countries. This paper outlines how this process was achieved in Canada; this may provide a model for other countries and jurisdictions as a part of occupational cancer prevention efforts.

Identifying occupational carcinogens: an update from the IARC Monographs.

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data.