A UK framework for the assessment and integration of different scientific evidence streams in chemical risk assessment.

BACKGROUND: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation. METHODS/APPROACH: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided. DISCUSSION/CONCLUSIONS: Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need.

Health impact assessment for air pollution in the presence of regional variation in effect sizes: The implications of using different meta-analytic approaches.

The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO2, O3 and PM2.5 with all-cause mortality, and PM2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran's Q test has a higher median power (0.71) than a test based on the moderators' coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09).

A critical review of the epidemiological evidence of effects of air pollution on dementia, cognitive function and cognitive decline in adult population.

Dementia is arguably the most pressing public health challenge of our age. Since dementia does not have a cure, identifying risk factors that can be controlled has become paramount to reduce the personal, societal and economic burden of dementia. The relationship between exposure to air pollution and effects on cognitive function, cognitive decline and dementia has stimulated increasing scientific interest in the past few years. This review of the literature critically examines the available epidemiological evidence of associations between exposure to ambient air pollutants, cognitive performance, acceleration of cognitive decline, risk of developing dementia, neuroimaging and neurological biomarker studies, following Bradford Hill guidelines for causality. The evidence reviewed has been consistent in reporting associations between chronic exposure to air pollution and reduced global cognition, as well as impairment in specific cognitive domains including visuo-spatial abilities. Cognitive decline and dementia incidence have also been consistently associated with exposure to air pollution. The neuro-imaging studies reviewed report associations between exposure to air pollution and white matter volume reduction. Other reported effects include reduction in gray matter, larger ventricular volume, and smaller corpus callosum. Findings relating to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease have been heterogeneous, as have observations on hippocampal volume and air pollution. The few studies available on neuro-inflammation tend to report associations with exposure to air pollution. Several effect modifiers have been suggested in the literature, but more replication studies are required. Traditional confounding factors have been controlled or adjusted for in most of the reviewed studies. Additional confounding factors have also been considered, but the inclusion of these has varied among the different studies. Despite all the efforts to adjust for confounding factors, residual confounding cannot be completely ruled out, especially since the factors affecting cognition and dementia are not yet fully understood. The available evidence meets many of the Bradford Hill guidelines for causality. The reported associations between a range of air pollutants and effects on cognitive function in older people, including the acceleration of cognitive decline and the induction of dementia, are likely to be causal in nature. However, the diversity of study designs, air pollutants and endpoints examined precludes the attribution of these adverse effects to a single class of pollutant and makes meta-analysis inappropriate.

Exposure to indoor and outdoor air pollution from solid fuel combustion and respiratory outcomes in children in developed countries: a systematic review and meta-analysis.

Epidemiological studies have shown a positive association between exposure to outdoor and indoor solid fuel combustion and adverse health effects. We reviewed the epidemiological evidence from Europe, North America, Australia and New Zealand on the association between outdoor and indoor exposure to solid fuel combustion and respiratory outcomes in children. We performed a systematic review and meta-analysis. Pooled relative risks (RRs) and 95% confidence intervals (CI) were calculated using random-effects models. We identified 74 articles. Due to limited evidence on other exposures and outcomes, we performed meta-analyses on the association between indoor wood burning exposure and respiratory outcomes. The RR for the highest vs the lowest category of indoor wood exposure was 0.90 (95% CI 0.77-1.05) considering asthma as an outcome. The corresponding pooled RRs for lower respiratory infection (LRI) and upper respiratory infection (URI) were 1.11 (95% CI 0.88, 1.41) and 1.11 (95% CI 0.85, 1.44) respectively. No association was found between indoor wood burning exposure and risk of wheeze and cough. Inconsistent and limited results were found considering the relationship between indoor wood burning exposure and other respiratory outcomes (rhinitis and hay fever, influenza) as well as indoor coal burning exposure and respiratory outcomes in children. Results from epidemiological studies that evaluated the relationship between the exposure to outdoor emissions derived from indoor combustion of solid fuels are too limited to allow firm conclusions. We found no association between indoor wood burning exposure and risk of asthma. A slight, but not significant, increased risk of LRI and URI was identified, although the available evidence is limited. Epidemiological studies evaluating the relationship between indoor coal burning exposure and respiratory outcomes, as well as, studies considering exposure to outdoor solid fuels, are too limited to draw any firm conclusions.

Using epidemiology to estimate the impact and burden of exposure to air pollutants.

This paper focuses on the use of results of epidemiological studies to quantify the effects on health, particularly on mortality, of long-term exposure to air pollutants. It introduces health impact assessment methods, used to predict the benefits that can be expected from implementation of interventions to reduce emissions of pollutants. It also explains the estimation of annual mortality burdens attributable to current levels of pollution. Burden estimates are intended to meet the need to communicate the size of the effect of air pollution on public health to policy makers and others. The implications, for the interpretation of the estimates, of the assumptions and approximations underlying the methods are discussed. The paper starts with quantification based on results obtained from studies of the association of mortality risk with long-term average concentrations of particulate air pollution. It then tackles the additional methodological considerations that need to be addressed when also considering the mortality effects of other pollutants such as nitrogen dioxide (NO2). Finally, approaches that could be used to integrate morbidity and mortality endpoints in the same assessment are touched upon. This article is part of a discussion meeting issue 'Air quality, past present and future'.

Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review.

It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, suggests that this is biologically plausible, particularly in the light of the current understanding of asthma as a complex disease with a variety of phenotypes. The epidemiological evidence for associations between ambient levels of air pollutants and asthma prevalence at a whole community level is unconvincing; meta-analysis confirms a lack of association. In contrast, a meta-analysis of cohort studies found an association between asthma incidence and within-community variations in air pollution (largely traffic dominated). Similarly, a systematic review suggests an association of asthma prevalence with exposure to traffic, although only in those living very close to heavily trafficked roads carrying a lot of trucks. Based on this evidence, the U.K.'s Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic. Nonetheless, the effect on public health is unlikely to be large: air pollutants are likely to make only a small contribution, compared with other factors, in the development of asthma, and in only a small proportion of the population.

Description of trihalomethane levels in three UK water suppliers.

Samples of drinking water are routinely analysed for four trihalomethanes (THMs), which are indicators of by-products of disinfection with chlorine, by UK water suppliers to demonstrate compliance with regulations. The THM data for 1992-1993 to 1997-1998 for three water suppliers in the north and midlands of England were made available for a UK epidemiological study of the association between disinfection by-products and adverse birth outcomes. This paper describes the THM levels in these three supply regions and discusses possible sources of variation. THM levels varied between different suppliers' water, and average THM levels were within the regulatory limits. Chloroform was the predominant THM in all water types apart from the ground water of one supplier. The supplier that distributed more ground and lowland surface water had higher dibromochloromethane (DBCM) and bromoform levels and lower chloroform levels than the other two suppliers. In the water of two suppliers, seasonal fluctuations in bromodichloromethane (BDCM) and DBCM levels were found with levels peaking in the summer and autumn. In the other water supplier, chloroform levels followed a similar seasonal trend whereas BDCM and DBCM levels did not. For all three water suppliers, chloroform levels declined throughout 1995 when there was a drought period. There was a moderate positive correlation between the THMs most similar in their structure (chloroform and BDCM, BDCM and DBCM, and DBCM and bromoform) and a slight negative correlation between chloroform and bromoform levels.

Water and health in Europe: a joint report from the European Environment Agency and the WHO Regional Office for Europe

Although some aspects of water quality and supply have improved in some countries over the last decade, progress has been variable. Renewed emphasis is being placed on microbial quality and the acknowledgement of previously unrecognized and re-emerging microbial and other hazards. Many of the suggested solutions are as applicable today as they were a decade ago. However, major changes in administrative arrangements affected many countries in Europe in the 1990s, including the supply of water and sanitation services, land-use activities, pollution control and activities related to public health surveillance. Partnerships and action were key themes of the Third Ministerial Conference on Environment and Health, held in London in June 1999. To this end the WHO Regional Office for Europe, in partnership with the United Nations Economic Commission for Europe, prepared a new Protocol on Water and Health to the 1992 Convention on the Protection and Use of Transboundary Watercourses and International Lakes. This publication provides information on many of the issues covered by the Protocol, such as adequate supplies of drinking-water and sanitation, water for irrigation and recreational use, monitoring of hazards, and public participation in decision-making. The evidence presented was collected through an extensive coordinated data-gathering process, in which many organizations and individuals throughout the European Region have cooperated. The 21st century will present a number of challenges to the aquatic environment. A coordinated approach to data collection, processing and management in Europe to support decision-making and to improve the reliability of environmental information will be essential to meet these challenges. This publication is aimed at a broad readership and is intended to present the key issues in a format that can be appreciated by policy-makers, professionals and the general public alike.