Evidence-based approaches to chemical risk assessment and risk management decision-making

Chemicals policy is designed to protect human and ecological health from the adverse effects that can result from exposure to manufactured chemical substances. It entails a complex process of regulatory chemical risk assessment and risk-management decision-making, drawing expertise from a diverse range of fields including toxicology and environmental health. However, these decision-making processes have come under increased scrutiny in recent years – criticized for bias, lack of transparency, rigor and a failure to identify unacceptable risks before widespread exposure occurs. This has resulted in calls for a more “evidence-based” approach, in which all relevant, available evidence is analyzed in a robust, transparent and reproducible manner. There is thus a growing need to incorporate methodological frameworks capable of facilitating evidence-based approaches to chemical risk assessment and regulatory decision-making. Such frameworks have been successfully developed in the field of medicine, which underwent a similar paradigm shift to that currently shaping chemical risk assessment, in the early 1990s. The gold-standard for evidence-based decision-making championed by the evidence-based medicine movement takes the form of systematic review. Systematic review describes a prescriptive and transparent method for collating, appraising and analyzing all available, relevant evidence in answer to a specific research question. By pooling the results of individual (independent) studies, systematic reviews synthesize conclusions which are not only more precise but are representative of an entire evidence-base. Now well established within clinical decision-making, the application of systematic review to chemical risk assessment is beginning to gain prominence. However, several challenges and barriers threaten to slow the uptake and quality of systematic review for chemical risk assessment. These include the prohibitively narrow focus of systematic reviews, which are at odds with the information requirements of regulatory decisions, and a mismatch in the resource availability within chemical risk assessment compared to the resource demands associated with systematic review. This thesis explores the challenges associated with implementing evidence-based approaches such as systematic review for chemical risk assessment, and identifies key methodological solutions: Chapter 1 examines the risk of bias assessment process – one of the most important but also most challenging aspects of systematic review methodology to adapt for environmental health. It examines the rationale for eschewing seemingly objective, quantitative approaches to assessing risk of bias in favour of seemingly more subjective, qualitative approaches. Through illustrative models, this thesis uncovers the mismatch between the mechanics of quantitative risk of bias assessment methods and the fundamental mechanics of risk of bias itself. Promoting understanding of this issue is increasingly important as systematic review gains prominence within chemical risk assessment – a field traditionally reliant on quantitative scoring methods for assessing the quality of included evidence. Chapter 2 considers the wider challenges to uptake of systematic review in environmental health, and proposes “systematic evidence mapping” as a methodological solution. A systematic evidence map is a queryable database of systematically gathered evidence which facilitates the broader identification of trends across the evidence-base. In this thesis, the potential utility of systematic mapping for existing and future chemical risk assessment workflows is characterized and critically assessed. A hypothetical but representative example (in which legacy flame retardants are prioritized for further regulatory assessment) is used to demonstrate the trend-spotting capacity of the methodology. Chapter 3 further explores the methodological adaptions required for effective implementation of systematic evidence mapping in chemical risk assessment and wider environmental health. By surveying current evidence mapping practice in environmental management (a field where the methodology is more mature), and qualitatively appraising this practice against the concepts of “data storage technology”, “data integrity”, “data accessibility”, and “transparency”, this thesis reveals the ill-suited nature of conventional tabular data structures for housing complex and highly connected environmental health/toxicology data. It identifies graph-based storage technologies as the most flexible and optimally suited data structures for the varied needs of chemical risk assessment workflows, and makes recommendations for their uptake in systematic evidence mapping. Chapter 4 of this thesis explores the practical implementation of graph-based solutions to evidence mapping in environmental health by conducting a proof-of-concept evidence mapping exercise, in which trends in the study of exposure-outcome associations for National Health and Nutrition Examination Survey (NHANES) datasets in the academic literature are explored. By contrasting this graph-based evidence mapping exercise to an equivalent tabular scoping review, this chapter demonstrates how significant gains in resolution and complexity can be achieved by adopting the graph data model – leading to greater insights than can be offered by traditional evidence-surveillance methods. The transparency, accessibility, interoperability and potential to expand graph-based evidence maps is also highlighted in this chapter by providing data models and methods which can be further adapted e.g. for the development of a suitable controlled vocabulary ontology. Finally, this thesis concludes by discussing the future direction of evidence-based chemical risk assessment and the role of graph-based evidence mapping within it, highlighting the need for further advances in automation and the uptake of data standards

Systematic evidence maps as a novel tool to support evidence-based decision-making in chemicals policy and risk management

Background While systematic review (SR) methods are gaining traction as a method for providing a reliable summary of existing evidence for health risks posed by exposure to chemical substances, it is becoming clear that their value is restricted to a specific range of risk management scenarios - in particular, those which can be addressed with tightly focused questions and can accommodate the time and resource requirements of a systematic evidence synthesis. Methods The concept of a systematic evidence map (SEM) is defined and contrasted to the function and limitations of systematic review (SR) in the context of risk management decision-making. The potential for SEMs to facilitate evidence-based decision-making are explored using a hypothetical example in risk management priority-setting. The potential role of SEMs in reference to broader risk management workflows is characterised. Results SEMs are databases of systematically gathered research which characterise broad features of the evidence base. Although not intended to substitute for the evidence synthesis element of systematic reviews, SEMs provide a comprehensive, queryable summary of a large body of policy relevant research. They provide an evidence-based approach to characterising the extent of available evidence and support forward looking predictions or trendspotting in the chemical risk sciences. In particular, SEMs facilitate the identification of related bodies of decision critical chemical risk information which could be further analysed using SR methods, and highlight gaps in the evidence which could be addressed with additional primary studies to reduce uncertainties in decision-making. Conclusions SEMs have strong and growing potential as a high value tool in resource efficient use of existing research in chemical risk management. They can be used as a critical precursor to efficient deployment of high quality SR methods for characterising chemical health risks. Furthermore, SEMs have potential, at a large scale, to support the sort of evidence summarisation and surveillance methods which would greatly increase the resource efficiency, transparency and effectiveness of regulatory initiatives such as EU REACH and US TSCA

Scottish Firefighters Occupational Cancer and Disease Mortality Rates: 2000-2020

Background Increased mortality from cancers and other diseases has been reported in USA, Canadian, and Nordic firefighters. However, UK firefighters are understudied. Aims To determine whether UK firefighters suffer increased mortality from cancers and other diseases when compared with the general population. Methods Mortality from cancer and other diseases in Scottish male firefighters between 2000 and 2020 was compared with the general Scottish male population and expressed as standardized mortality ratios (SMRs) (with 95% confidence intervals, CI). Results Significant overall excess cancer mortality was found for Scottish firefighters compared with the general population (SMR 1.61, CI 1.42-1.81). Scottish firefighters were nearly three times more likely to die of malignant neoplasms (unspecified sites) (SMR 2.71, CI 1.71-4.00). Excess cancer mortality was also found for several site-specific cancers, including prostate (SMR 3.80, CI 2.56-5.29), myeloid leukaemia (SMR 3.17, CI 1.44-5.58), oesophagus (SMR 2.42, CI 1.69-3.29) and urinary system (kidney and bladder) (SMR 1.94, CI 1.16-2.91). Mortality from neoplasms of unknown behaviour was over six times greater in Scottish firefighters (SMR 6.37, CI 2.29-12.49). Additionally, significantly higher mortality was found for: acute ischaemic heart diseases (SMR 5.27, CI 1.90-10.33), stroke (SMR 2.69, CI 1.46-4.28), interstitial pulmonary diseases (SMR 3.04, CI 1.45-5.22), renal failure (SMR 3.28, CI 1.18-6.44) and musculoskeletal system diseases (SMR 5.64, CI 1.06-13.83). Conclusions UK firefighters suffer significant excess mortality from cancer and other diseases when compared with the general population. Preventative health monitoring and presumptive legislation are urgently required to protect UK firefighters’ health

Contamination of UK firefighters personal protective equipment and workplaces

Firefighters’ personal protective equipment (PPE) is a potential source of chronic exposure to toxic contaminants commonly released from fires. These contaminants have also been found in fire stations. However, little research characterises the routes via which fire contaminants travel back to fire stations. The UK Firefighter Contamination Survey provides information on firefighters’ PPE provision, decontamination, and storage practices. All serving UK firefighters were eligible to take part in the survey, which comprised 64 questions. A total of 10,649 responses were included for analysis, accounting for roughly 24% of the UK’s firefighting workforce. Results revealed that most firefighters (84%) de-robe contaminated PPE/workwear after re-entering the appliance cab. There was a significant decreasing tendency to send PPE for cleaning after every incident with increasing seniority of role, length of service, and fire attendance frequency. Around one third of firefighters cleaned PPE after every incident. A number of issues were linked to external professional cleaning services, e.g. shrinkage, fit, turn-around time, and stock of reserve/pooled PPE. PPE storage was found to be a potential source of cross contamination, with almost half of firefighters (45%) indicating clean and dirty PPE is not stored separately. More than half of firefighters (57%) stored fire gloves (an item sent for professional decontamination by only 19% of firefighters, and never cleaned by 20%) within other items of PPE such as helmets, boots and tunic/trouser pockets. The survey’s results can be used to target gaps in decontamination measures within UK Fire and Rescue Services

Mental health of UK firefighters

Exposure to trauma, high-stress situations, and disrupted sleep are well known risk factors affecting firefighters’ mental health. Little is known about the association between firefighters’ exposure to fire contaminants and mental health disorders. The UK Firefighter Contamination Survey assessed firefighters’ health and capacity for occupational exposure to contaminants. Participants were invited to anonymously complete its 64 questions online. Logistic regression analyses assessed the associations between self-reported mental health disorders and proxies of contaminant exposure. Results found that firefighters who notice soot in their nose/throat for more than a day after attending fires (Odds Ratio (OR) = 1.8, 1.4–2.4), and those who remain in their personal protective equipment (PPE) for over 4 h after fires (OR = 1.9, 1.2–3.1), were nearly twice as likely to report mental health disorders. Significantly increased odds ratios for all three outcomes of interest (anxiety, depression and/or any mental health disorders) were also found among firefighters who take PPE home to clean. Sleeping problems were reported by 61% of firefighters. These firefighters were 4.2 times more likely to report any mental health disorder (OR = 4.2, 3.7–4.9), 2.9 times more likely to report anxiety (OR = 2.9, 2.4–3.5) and 2.3 times more likely to report depression (OR = 2.3, 1.9–2.8) when compared to firefighters who did not report sleep issues. Effective decontamination measures within UK Fire and Rescue Services, together with firefighters’ wellness, may play a crucial role in protecting firefighters’ mental health

Knowledge Organization Systems for Systematic Chemical Assessments

BACKGROUND: Although the implementation of systematic review and evidence mapping methods stands to improve the transparency and accuracy of chemical assessments, they also accentuate the challenges that assessors face in ensuring they have located and included all the evidence that is relevant to evaluating the potential health effects an exposure might be causing. This challenge of information retrieval can be characterized in terms of "semantic" and "conceptual" factors that render chemical assessments vulnerable to the streetlight effect. OBJECTIVES: This commentary presents how controlled vocabularies, thesauruses, and ontologies contribute to overcoming the streetlight effect in information retrieval, making up the key components of Knowledge Organization Systems (KOSs) that enable more systematic access to assessment-relevant information than is currently achievable. The concept of Adverse Outcome Pathways is used to illustrate what a general KOS for use in chemical assessment could look like. DISCUSSION: Ontologies are an underexploited element of effective knowledge organization in the environmental health sciences. Agreeing on and implementing ontologies in chemical assessment is a complex but tractable process with four fundamental steps. Successful implementation of ontologies would not only make currently fragmented information about health risks from chemical exposures vastly more accessible, it could ultimately enable computational methods for chemical assessment that can take advantage of the full richness of data described in natural language in primary studies. https://doi.org/10.1289/EHP6994

Culture and awareness of occupational health risks amongst UK firefighters

Firefighters are exposed to toxic chemicals not only from the fire incidents they attend, but also from their contaminated station and/or personal protective equipment (PPE). Little is currently known about firefighters’ awareness, attitudes, and behaviours towards contaminants which was assessed in the UK firefighter contamination survey. Results revealed that lack of training on fire effluents and their health outcomes are strongly associated with increased fire smoke/contaminant exposure. Notably, untrained firefighters were at least twice as likely to: never clean personal protective equipment (PPE) (Crude Odds Ratio, OR 2.0, 1.5–2.7), infrequently send their PPE for professional cleaning (OR 2.0, 1.6–2.4), remain in the workwear (t-shirt etc.) worn while attending a fire incident (OR up to 3.6, 2.3–5.6), and indicate that cleaning at fire stations is not taken seriously (OR 2.4, 2.2–2.6). Firefighters personally viewing contamination as a “badge of honour” (BoH) were at least twice as likely to: remain in contaminated PPE after fire incidents (OR 2.3, 1.4–3.9), eat with sooty hands (OR 2.2, 1.9–2.5), notice soot in the nose/throat (OR 3.7, 2.7–5.2), and smell fire smoke on the body for more than a day after incidents (OR 2.0, 1.6–2.4). They were also more likely to indicate that cleaning at fire stations is not taken seriously (OR 2.5, 2.2–2.9) and that fire stations smell of smoke always/most of the time (OR 2.3, 2.0–2.6). Strong links were also found between belief in the BoH and never cleaning PPE (OR 1.9, 1.4–2.7), and eating while wearing contaminated PPE (OR 1.8, 1.5–2.2)

Cancer incidence amongst UK firefighters

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters’ PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters’ risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35–39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1–3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1–5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2–2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0–1.7); working in a station that smells of fire (OR = 1.3, 1.0–1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1–1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0–1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2–2.0)